WO2000059574A1

WO2000059574A1 - Intra cavity site-specific delivery probe

Info

Publication number: WO2000059574A1
Application number: PCT/US2000/008755
Authority: WO
Inventors: Alexander V. Kirichenko; Tyvin A. Rich
Original assignee: The University Of Virginia Patent Foundation
Priority date: 1999-04-01
Filing date: 2000-03-31
Publication date: 2000-10-12
Also published as: AU4189400A

Abstract

This invention is a delivery system (100) for delivering a substance to a body surface. Said delivery system includes an elongated catheter (100) having a proximal end (110), and a distal end (130). The elongated catheter (100) has a main body portion (120) having at least two lumens extending from the proximal end (110) to a position near the distal end (130). A first balloon portion (140) is positioned around the main body (120) of the catheter (100) near the distal end (130).

Description

INTRA CAVITY SITE-SPECIFIC DELIVERY PROBE

Related Application

This application claims the benefit of U.S. Provisional Application Serial Number 60/127,317 and the benefit of U.S. Provisional

Application Serial Number 60/127,318 both filed April 1, 1999 under 35 U.S.C. 119(e).

Field of the Invention The present invention relates to the field of delivering small amounts of material to specific locations within an object, such as the body of a mammal. More particularly, this invention relates to an apparatus and method for placing a delivery system within an object, fixing the delivery system within the object and dispensing and monitoring the flow of material through the delivery system. Background of the Invention

Acute mucocutaneous toxicity of the aero digestive tract caused by high dose radiotherapy, accelerated radiotherapy schedules, and especially with chemoradiation (irradiation and chemotherapy given concurrently) can be dose limiting. When acute mucosal injury does not heal, consequential reactions occur leading to chronic or late injury. With the use of more aggressive chemoradiation programs, acute mucosal injury is now considered to be the dose limiting toxicity. In practical terms, the concept of normal tissue tolerance is based on the biologic response of the most sensitive patients in a heterogeneous population. New methods are needed to discriminate patients at risk for unacceptable normal tissue injury or, in other words, to be able to predict those who are sensitive from those who are resistant to toxic treatment. One possibility is to measure abnormalities in absorption of various nutrients, including carbohydrates, amino acids, proteins, vitamins, electrolytes and bile acids [for example: A. B. R. Thompson et al, Ra . Res,_; 107, 344 (1986).], as these reflect functional disorders of the intestine created by ionizing irradiation. Most studies, however, have been performed on rodents using either in vivo or in vitro perfusion techniques that have limited clinical applicability [J. Overgaard et al, Radintber. One, i&, 71 (1990) ]. Another possibility is to monitor intestinal absorption of technetium pertechnetate (Na^TcOJ) as a measure of radiation- induced intestinal damage. This method is referred to as dynamic enteroscintigraphy, and is based on measurement of the rate of isotope uptake from the intestine into systemic circulation (Kirichenko AN, Mason K, Straume M, Teates CD, and Rich TA. Nuclear scintigraphic assessment of radiation- induced intestinal dysfunction. Radiation Research 153:164-172, 2000).

None of these methods are anatomically site specific because they reflect the fate of the tracer absorbed by the entire GI tract. Thus, there is a need for a device that could deliver small amount of a radioactive tracer to a specific sites of the mucosal surface in order to monitor site-specific absorption function. There is also a need for a delivery system capable of delivering chemotherapeutic drugs, or radio/chemo protectors, imaging agents, gene vectors etc. to specific sites of the mucosal surface. For example, site specific delivery of radiation or chemo protectors to the target tissues in high therapeutic concentrations (such as delivery of these drugs to the anterior rectal wall during prostate cancer radiation therapy) is especially advantageous as the drugs have high level of toxicity when injected systemically through intravenous injections (M. Hensley, L.M. Schuchter, C. Lindley et al. American Society of Clinical Oncology Clinical Practice Guidelines for the Use of Chemotherapy and Padiotherapy Protectans. J Clin One 17:3333-3355, 1999).

In general, there is a need for a non-invasive delivery system capable of release of controlled amounts of fluids, such as chemotherapeutic drugs, radiation or chemotherapy protectors, radiopharmaceuticals, non- radioactive imaging agents, gene vectors etc. onto specific sites of the mucosal/serosal surfaces. Furthermore, there is a need for a device, which can be held in place within a body cavity as a drug or other agent, is delivered. In addition, there is a need for a detection probe that can be placed inside the site- specific delivery device in order to monitor the absorption rate of the radioactive tracers (such as amino acids, carbohydrates, microelements, and vitamins, drugs etc.) labeled with γ- or β-emitters. Summary of the Invention

A delivery system for delivering a substance to a body surface, said delivery system includes an elongated catheter having a proximal end and a distal end. The elongated catheter has a main body portion having at least two lumens extending from the proximal end to a position near the distal end. A first balloon portion is positioned around the main body of the catheter near the distal end. The first balloon portion is in fluid communication with at least one of the lumens in the catheter. A second balloon portion is positioned over the first balloon portion. The second balloon portion has an aperture. A delivery tube has a first end and a second end. One of the delivery tube is positioned near the proximal end of the catheter. The other end of the delivery tube is positioned near the aperture in the second balloon portion. The delivery tube is captured between the first balloon portion and the second balloon portion. In one embodiment, the end of the delivery tube actually crosses the aperture when in a deflated or flattened condition. A first portion of the delivery tube passes through another lumen in the catheter. One end of the fluid delivery can couple with a syringe such that a selected amount of fluid can be passed through the delivery tube from the end near the proximal end to the end near the aperture in the second balloon portion. The first balloon portion is inflated with a fluid to fix the position of the distal end of the catheter with respect to a body and to bring the delivery tube into close proximity with the body.

In two other embodiments, scintiallation a scintillation element is used to monitor flow rate of a radioactive trace in a fluid. Monitoring the flow rate of the fluid is used as a diagnostic indicator of cell health in the intestine or any vessel having a mucosal layer. A scintillation fluid or a scintillation crystal is used to monitor the rate of flow of fluid through the delivery tube. In one embodiment, an optical cable is passed through another of the lumens. The optical cable passes into the inflatable space associated with the first balloon portion and the first balloon portion. In one of the two embodiments, the balloon portion is inflated with a scintillation fluid. The delivery tube is used to deliver a fluid including a radioactive component, such that as the radioactive component decays the scintillation fluid produces a light incident. The light is carried by the optic cable from the distal end to the proximal end of the catheter. A photo multiplier is attached to the fiber optic cable at the proximal end of the catheter.

A counter is attached to the photo multiplier to count the number of incidents of light over time. A processor correlates the number of counts received by the counter to a rate of fluid flow through the delivery tube. A light shifting device attached to the end of the optical cable passing into the inflatable space associated with the first balloon portion. A nontoxic scintillation fluid is used in one embodiment.

In the other embodiment using scintillation, a scintillation crystal is attached to one end of the fiber optical cable and the scintillation crystal is positioned within the inflatable space associated with the first balloon portion.

When the scintillation crystal is used, the first balloon portion may be inflated with any gas, such as air.

A method for delivering a substance to a body surface includes providing a delivery system capable of intracavitary operation. Positioning the delivery system adjacent to the body surface, and deploying the delivery system adjacent to the body surface so that the substance is delivered to said body surface.

A method for assessing the functional integrity of a mucosal membrane includes administering a reagent to said mucosal membrane, employing a dynamic scintigraphy to measure the absorption in said mucosal membrane of said reagent, and collecting data from said dynamic scintigraphy. Advantageously, the delivery system is capable of delivering small amounts of fluids, such as drugs or radial protectors and radio nuclides, to specific positions within a body while being held in place within a body as a drug or other treatment is delivered to a specific portion of the body. The delivery system can also be positioned near the area to which a drug or other fluid needs to be delivered. The delivery system can be easily and controllably released and removed after an appropriate dosage is delivered to the specific portion of the body. The amount of fluid passing through the drug delivery system. The rate at which the fluids can be delivered can also be determined, especially for radio nuclides or radio protectors, delivered to a certain area of the body. The device can be used in a non invasive manner or can be inserted via an operating channel. Brief Description of the Drawings

FIG. 1 is a side view of a first embodiment of a delivery system for delivering fluids to specific positions within a body. FIG. 2 is a cross sectional view of the first embodiment of the delivery system along line 2-2 of FIG. 1.

FIG. 3 is a side view of the distal end of the first embodiment of the delivery system in an uninflated state. FIG. 4 is a side view of the distal end of the first embodiment of the delivery system in an inflated state. FIG. 5 is a cross sectional view of the distal end of the first embodiment of the delivery system in an inflated state along line 5-5 of FIG. 4. FIG. 6 is a side view of a second embodiment of the distal end of the delivery system in a deflated state. FIG. 7 is an end view of the second embodiment of the distal end of the delivery system in a deflated state.

FIG. 8 is a side view of a second embodiment of the distal end of the delivery system in an inflated state. FIG. 9 is an end view of the second embodiment of the distal end of the delivery system in an inflated state. FIG. 10 is a side view of a third embodiment of the distal end of the delivery system in an inflated state. FIG. 11 is an end view of the third embodiment of the distal end of the delivery system in an inflated state. FIG. 12 is an side view of one embodiment of the delivery system positioned in contact with the rectal wall of a mammal.

FIG. 13 is a perspective view of the distal end of one embodiment of the delivery system in a deflated or flattened state. FIG. 14 is a perspective view of the distal end of one embodiment of the delivery system in an inflated or deployed state. FIG. 15 shows a kit including a delivery system for delivering fluids to specific positions within a body, a fluid to be delivered, a syringe and information related to use of the kit. Description of the Preferred Embodiment

In the following detailed description of the preferred embodiments, reference is made to the accompanying drawings which form a part hereof, and in which are shown by way of illustration specific embodiments in which the invention may be practiced. It is to be understood that other embodiments may be utilized and structural changes may be made without departing from the scope of the present invention.

FIG. 1 is a side view of one type of an elongated delivery system 100 for delivering fluids to specific areas or parts of the body of a mammal. The delivery system may also be termed generally as a catheter 100. The catheter 100 is comprised of a proximal end 110, a catheter body 120, and a distal end 130. The catheter body 120 is cylindrical in shape. The catheter body 120 is a tubing material formed from a polymer biocompatible for implantation, and preferably the tubing is made from a silicone rubber polymer. The silicone rubber polymer tubing contains several lumens. The catheter body 120 includes a number of lumens 210, 220, 230 and 240 (shown in FIG. 2) which are elongated tubular openings which generally run substantially the length of the catheter 100. The lumens are adapted for carrying flexible elements such as electrical conductors, fluid delivery tubes, fiber optic cables or the like. The distal end of 130 includes a doughnut shaped two layer wall latex balloon 140. The distal end 130 has a blunt rounded tip 132 and a third layer thin latex sleeve 142 covering the balloon 140 at and near the distal end of the delivery system 100. In one embodiment, polyethylene tubing (available from LNTRAMEDIC Inc). is used. Tubing diameters may vary. In one embodiment, tube in use has an inner diameter of approximately 0.5mm and an outer diameter - 0.96mm. Of course, the tubing used as the outer second wall or latex sleeve 142 must be biocompatible and of sufficient strength and durability to undergo repeated stretching without failure.

The outer latex layer 142 includes a 1 mm diameter opening 144 in the middle of the outermost layer. In flattened or deflated condition, the surface of fhe catheter 100 is completely smooth, so there is no threat damage to the body upon insertion. The delivery tube 300 may be placed on the outer surface of the catheter. The distal end of the delivery tube 310 can then be tucked into the aperture 144. Optionally, a marker 180 is associated with the distal end 130 of the delivery system. The marker 180 is shown in FIG. 1 but not in the other figures. The marker 180 is viewable by x-ray or other means for detecting the position of the distal end 130 of the delivery system 100. The marker is typically at a fixed position with respect to the aperture 144 so that the position of the aperture 144 can be determined from the position of the marker 180. In one embodiment, the marker 180 is a lead rod or cylinder. In another, the marker 180 is a metallic ball such as a common bb. The marker may be near the aperture 144 or on the other side of the balloon 140 away from the aperture 144. As long as the marker 180 is at a fixed relation from the aperture 144, the person monitoring the distal end 130 of the delivery system 100 can determine the position of the aperture 144 so that the distal end 310 of the delivery tube 300 can be precisely placed near a desired portion of the body. The marker 180 must be made of a material which is visible by the particular imaging device used to monitor the position of the distal end 130 of the delivery system 100.

The proximal end 110 is adapted to receive syringes or other similar devices for controllably delivering fluid through the catheter. The catheter 100 may also attach to a photo detector and monitoring electronics 150. The photo detector and monitoring electronics 150 contains electronics to sense various pulses of the light and also interpret signals input to the photo detector and monitoring electronics 150. It should be noted that there are numerous types of connector terminals which connect to a photo detector and monitoring electronics 150.

FIG. 2 is a cross sectional view of the first embodiment of the delivery system or catheter 100 along line 2-2 of FIG. 1. The delivery system includes four lumens 210, 220, 230 and 240. The lumens 210, 220, 230 and 240 may also be referred to as channels. In some embodiments of this invention less than four lumens 210, 220, 230 and 240 may be needed. A fluid delivery tube 250 is shown positioned in channel or lumen 230. In one embodiment, the delivery system 100 needs only two lumens. It should be noted that the diameter of the lumens 210, 220, 230 and 240 must have sufficient diameter to allow objects to pass through the lumens 210, 220, 230 and 240. It should also be noted that having less lumens 210, 220, 230 and 240 may allow for a smaller diameter main body 120 of the delivery system or catheter 100. Furthermore, having lumens 210, 220, 230 and 240 with smaller diameters will also allow for a smaller diameter main body 120 of the delivery system or catheter 100. The number of lumens 210, 220, 230 and 240 may be varied without departing from the spirit of the invention.

FIG. 3 is a side view of the distal end 130 of the first embodiment of the delivery system 100 in an uninfiated state. The distal end 130 of the delivery system 100 is also known as a probe. The distal end 130 includes the balloon 140 with its three layers 142. In the outer layer of the probe or distal end of the catheter delivery system 100 there is an aperture 144. Also shown is a tracer or dosage delivery tube 300. The dosage or tracer delivery tube 300 has a first end at the proximal end 110 of the catheter and has a second end 310 which terminates near the opening 144 in the outer layer of the balloon 140. It should be noted that the second or distal end 310 of the delivery tube 300 passes across the aperture 144. This allows the distal end 310 of the delivery tube 300 to be safely tucked away which prevents or lessens the possibility that the delivery system or catheter 100 will catch or damage tissue while being inserted. Also shown schematically is a lumen 210 through which air or another fluid can be pumped to inflate the balloon 140. FIG. 4 is a side view of the distal end 130 of the first embodiment of the delivery system 100 in an inflated state. Air is pumped into the lumen 210. The lumen includes a one-way valve 410 which helps the air or other fluids stay within the balloon 140. The dosage or tracer delivery tube 300 has a portion 302 which is captured between the outer layer of the probe or the outer latex layer of the balloon and an inner latex layer of the balloon. This can be seen as the end of the dosage or tracer delivery tube 310 moves outwardly from the main body of the probe or catheter. By inflating the balloon 140, the aperture 144 in the balloon 140 becomes enlarged. In addition, the distal end 310 of the delivery tube 300 moves with respect to the opening so that the end 310 moves into the aperture 144 and can emerge out of the opening. A portion 302 of the delivery tube 310 remains captured between the balloon 140 and the second outer wall portion 142 is moving distal end 310 of the delivery tube 300. Also shown in FIG. 4 is a second dosage/tracer delivery tube 300'. It should be noted that there is no set number of dosage or tracer delivery tubes 300 that need be associated with the probe or delivery device 100. A delivery device could be formed having many more apertures (not shown) and still be within the spirit of the invention. Furthermore, the spacing of the apertures does not have to be equal about the second outer wall portion 142. For example, one application is to produce a pattern which resembles a shower head. Other applications would be to have one aperture at the tip 132 of the delivery device and another along the side as shown in FIG. 4. A single dosage tracer delivery tube 300 as well as a plurality of dosage tracer delivery tubes 300, 300' are contemplated by this invention.

Using more than one delivery tube 300, 300' has several advantageous applications. For example, two reactive fluids can be placed in each of the delivery tubes 300, 300'. The reaction can take place at the site within the body. In addition, the same fluid may be delivered to different areas of the same body part. This is useful when measuring the takeup rate of the fluid to determine the absorption rate in the intestines. The second tube 300' can be used as a control to see if the first tube 300 is clogged or otherwise damaged. The two tubes may also be monitored to determine more precisely the location of cell damage in the intestine of a mammal.

FIG. 5 is a cross-sectional view of the distal end 130 of the first embodiment of the delivery system 100 in an inflated state along line 5-5 of FIG. 4. In FIG. 5 the balloon 140 is shown in additional detail. The balloon is a donut-shaped type balloon which wraps around the main body of the distal end 130 of the probe or catheter 100. The balloon 140 includes a surface 500 that contacts the main body of the probe 130. The balloon 140 includes an aperture 510 which places the interior of the balloon 140 in fluid communication with the lumen 210 used to pump air or another fluid into the interior of the balloon 140. Stretched over the first balloon 140 is a second balloon or latex surface 142. The second latex surface 142 includes the opening 144. A tracer delivery or dosage delivery tube 300 is captured or pinched between an exterior portion of the balloon 140 and the outer latex or second balloon covering 142. It also should be noted that the balloon portion has three layers including the layer 500 contacting the distal end 130 of the catheter 100, the portion that moves away from the catheter when inflated, as well as the outer latex layer or second balloon 142. In other words, a triple-layer balloon is placed on the distal end 130 of the catheter 100. As can be seen from FIG. 5, by inflating the balloon 140 the tracer delivery tube or dosage delivery tube 300 remains captured between the balloon 140 and an outer skin 142. Also as can be seen from FIG. 5, the end 310 of the dosage or tracer delivery tube 300 moves away from the main body of the catheter 100. Thus, the drug delivery system 100 or the catheter 100 can be deflated and moved into position within a body or in position with respect to a specific body surface and then inflated so that the outer walls of the balloon and specifically the latex portion 142 contacts a portion of the body. Inflating a balloon not only moves the end of the dosage or tracer delivery tube 300 into contact with a particular body surface, but it also holds the distal end 130 of the catheter 100 in place. After the ends 310 are determined to contact a selected body part, then a syringe may be used or placed into the other end of the tracer delivery tube associated with the proximal end of the catheter 100. The syringe can be used to apply a pressure used to deliver a tracer fluid or fluid containing a dosage or any selected fluid from the proximal end 110 of the catheter to the end 310 of the tracer delivery tube or dosage delivery tube 300. This particular invention has very wide applications. It can be used anywhere it is necessary to deliver a small amount of fluid, such as a tracer delivery fluid, a dosage of medicine or any other selected fluid to a particular portion of the body. It should also be noted that the dimensions of the catheter and the tracer delivery tube may be formed for the particular body portion which it is to contact or it is desired to deliver a drug or tracer fluid to. For example, different dimensions may be used to deliver selected fluids to the bile duct. Still other selected dimensions may be used in forming a delivery system 100 for delivering selected fluids to the pancreatic duct. In the pancreatic duct, for example, a probe which is approximately 4 millimeters in diameter and 3 centimeters in length is used to enter the pancreatic duct. Although the delivery system 100 is useful for any surface within a body, the delivery system 100 is especially useful for any vessel having a mucosal surface. In use, the probe or distal end 130 of the catheter, which includes the balloons and delivery tubes 300, 300', are delivered to a void within the body. Inflating the balloon 140 fills the void and also places the end 310 of the delivery tube 300 in contact with the inner walls of the void within a body. The probe or distal end 130 of the catheter 100 stays in place as long as the balloon 140 is inflated. The distal end or probe 130 stays in place within the body as long as the balloon 140 remains inflated. Thus, the probe remains stationary or substantially stationary with respect to a body part while the delivery tube 300 can be used to deliver the selected fluid to the body part. It should be noted that the end catheter can be located within the body during insertion by using x-ray or fluoroscopy. By noting or observing where the distal end 130 or probe of the delivery device is located using x-ray or fluoroscopy, the exact position of the probe or distal end 130 of the delivery device or delivery system 100 can be determined. The marker 180 is used to determine the exact location of the opening or aperture 144 in the outer layer 142 of the probe or delivery system 100. The probe or delivery device 100 is useful in delivering small amounts of a selected fluid to a very specific body part. It should be noted that any type of fluid may be delivered to a specific body portion through one or more delivery tubes 300, 300'. For example, radionuclides, radioprotectors, nucleaui acids, viral vectors or gene therapy vectors are just a few examples of the fluid that may be delivered to a specific body part. Delivery System with Monitoring using a Scintillation Crystal

FIG. 6 is a side view of a second embodiment of the distal end 130 of a delivery system 100 in a deflated state. In this particular embodiment, the balloon 140 is stretched over the distal end 130 of the catheter 100. A second balloon 142 is also stretched over the distal end 130 of the catheter 100. The second balloon 142 or latex surface 142 includes an aperture 144 which is at the distal end or tip 132 of the catheter 100. The tip of the delivery tube 131 or end of the delivery tube 131 is positioned at or near the aperture 144. FIG. 7 shows an end view of the second embodiment of the delivery system 100. In short, FIG. 7 shows the distal end 130 and more specifically the tip 132 of the catheter 100. The exterior balloon surface 142 includes an aperture 144. The delivery tube shown in FIGS. 9-11 passes through the catheter and terminates near and has its end 131 which terminates near the opening 144 in the balloon 142. It should be noted that in the second embodiment the probe or distal end 130 of the delivery device is smooth so that it can be inserted without damaging tissue or without snagging or catching on tissue as it is in route to the selected spot within a body.

FIG. 8 is a side view of the second embodiment of the distal end 130 of the delivery system 100 in its inflated state. The drug delivery system includes lumen 210 through which air or another inflatable fluid or fluid for inflating the balloon 140 is passed. The delivery device also includes a delivery tube 300. The delivery tube is adapted for receiving a syringe at the proximal end. Also running down another lumen of the catheter is a fiber optic cable 800. The fiber optic cable enters into the inflated space of the balloon 140. A scintillation crystal 810 is attached to the distal end of the fiber optic cable which extends into the inflated portion of the balloon 140. At the proximal end 110 of the delivery system 100 is a photo multiplier and counter and a processor, depicted by reference numeral 820 in FIG. 8. In the second embodiment, a radioactive fluid is passed through the delivery tube 300. As the radioactive fluid passes through the tube it decays giving off radioactive particles. When the radioactive particles strike the scintillation crystal 810, it causes an incidence of light or a light event which is passed through the fiber optic cable to the photo multiplier and counter represented by reference numeral 820. A microprocessor or other processor counts the number of light incidents received by the counter over a selected amount of time to determine the rate at which the particular radioactive fluid is passed through the delivery tube 300. In this particular embodiment, air is used to fill the balloon 140 or bladder. It can be seen that by inflating the balloon 140, the tip or end 310 of the delivery tube 300 is moved out from the tip or distal end 130 of the catheter 100.

FIG. 9 is an end view of the second embodiment of the distal end 132 of the delivery system 100 in an inflated state. In this particular end view, the aperture 144 in the second balloon 142 is marked clearly seen. The scintillation crystal 810 is shown in phantom as is the tracer delivery tube or delivery tube 300. The end 310 of the delivery tube 300 terminates near the aperture 144 in the second balloon 142. Delivery System with Monitoring using a Scintillation Fluid

Now turning to FIG. 10, a side view of a third embodiment of the distal end 132 of a delivery system is shown in inflated state. It should be noted that the third embodiment was not shown in its deflated state since it will appear essentially the same as the second embodiment in its deflated state shown in FIGS. 6 and 7. Like the second embodiment, the main body of the catheter 100 includes a fiber optic cable 800. The fiber optic cable 800 extends into the inflated portion of the balloon 140. The balloon 140 is filled with a scintillation fluid 1000, rather than with air as in the previous embodiments. The scintillation fluid 1000, in one embodiment, is a non-toxic scintiallation fluid. The delivery tube 300 carries a radioactive fluid such as used for chemotherapy or delivering of a tracer to a specific body part. As the radioactive fluid passes through the delivery tube 300 it produces or sheds radioactive particles which induce a light incident in the scintillation fluid 1000 within the balloon 140. The light incidents are picked up by the fiber optic cable 800 and delivered via the fiber optic cable 800 to the photo amplifier and counter and processor depicted by box 820 at the proximal end 110 of the catheter 100. Using the scintillation fluid 1000 is advantageous in that it is capable or more sensitive to beta particles. When using a scintillation crystal 810, the scintillation crystal is not sensitive to beta particles. In contrast, the scintillation fluid 1000 is very sensitive to beta particles and will produce a light incident in the presence of a beta particle. The scintillation fluid is approximately 1000 to 100,000 times more sensitive to beta particles than the scintillation crystal 810. This means that smaller amounts of fluid may be used to obtain a monitoring type reading. An additional advantage is that there are many more fluids capable of carrying a tracer which emits beta particles. For example amino acids, vadimonies, and carbohydrates are all fluids that can carry beta particles and can be used to detect the amount of uptake or absorption in a vessel with a mucosal layer. The increased sensitivity also allows for less time being needed to make readings related to the uptake. In still another embodiment, the fiber optic cable is provided with a light shifting device so that the fiber optic cable can sense light incidences around a 360 degree area. A light shifting device , such as a wavelength shifting fiber cable can be purchased from Bicron Inc., or other companies manufacturing small intraoperative probes.

FIG. 11 is an end view of the third embodiment of the distal end 132 of the delivery system 100 shown in its inflated state. In this particular embodiment, the balloon 140 can be seen as is the second balloon 142 in the aperture therein 144. The tracer delivery tube or delivery tube 300 is shown in phantom. The end of the delivery tube 310 is positioned near the opening 144 in the second balloon 142. The scintillation fluid 1000 is shown within the balloon 140. FIG. 12 is an x-ray side view of one embodiment of the delivery system positioned in contact with the rectal wall of a mammal. The distal end 130 of the delivery device 100 is positioned in contact with the rectal wall of a mammal. The delivery system is passed through the rectum of the mammal to the rectal wall. FIGs. 13 and 14 are perspective views of the distal end of one embodiment of the delivery system. In FIG. 13 the distal end is in its deflated or flattened state. The distal end 130 of the probe or delivery system 100 is sufficiently smooth so ease insertion of the delivery system to a specific body portion of a mammal. FIG. 14 shows the distal end in an inflated state. FIG. 15 shows a kit 1530 including a delivery system for delivering fluids to specific positions within a body, a fluid 1500 to be delivered, a syringe 1510 and information 1520 related to use of the kit, namely instructions for a particular application. For example, it is possible that a different size delivery system 100 may be sold with different drugs, such a radioactive tracer, a radio protector, a chemotherapy drug, or some other selected drug. The drug may come prepackaged in a syringe within the kit. This would provide for ease of application in an operating suite. The kit could come in a sterilized package and everything could be provided for the particular application by a nurse and available to a surgeon for use. Different sizes may be needed to work in preferred or selected operating channels.

The probe or delivery system 100 provides a method for delivering a substance to a body surface. The method includes providing a delivery system capable of intracavitary operation and positioning the delivery system 100 adjacent to said body surface. Next, the balloon 140 is deployed or inflated as the delivery system 100 is adjacent to the body surface. The substance is delivered to said body surface by the delivery system 100. The probe or delivery system can be used to assess the functional integrity of a mucosal membrane. The method includes administering a reagent to said mucosal membrane while employing a dynamic scintigraphy to measure the absorption in said mucosal membrane of said reagent. The method also includes collecting data from the dynamic scintigraphy. Several specific example applications of the invention are set forth below. It should be noted that these examples are not exclusive and that the delivery device can be used in many applications not listed herein and still be within the spirit of the invention.

One diagnostic application is to measure the rate of takeup of a particular fluid at one portion of the body and then to deflate the balloon 140 and move it to another portion of the body where it is reinflated and then more fluid is delivered to the different portion of the body. It is envisioned that the delivery system could be used for diagnostic purposes to determine the general health of the GI tract for example by inserting the delivery system to a first position, delivery fluid and measuring the take up rate and then repeating this procedure at a second position within the GI tract. Abnormal absorption rates would indicate a problem and tissue that may have a problem. Once identified, further tests could be conducted to isolate a problem. In one embodiment, the distal end 130 of the delivery system 100 is placed in the most distant position as the first position. Subsequent readings are taken at positions as the delivery system is retracted from the body. Although most times the distal end 310 of the delivery tube 300 is covered or tucked in after deflating the balloon 140, this procedure will be less damaging if the distal end 310 of the delivery tube 300 might not get tucked in again.

Example 1 : Delivery System For Delivering Tracer to Rectal Mucosa The delivery device 100 may be used for intracavitary site- specific delivery of radioactive tracer (for instance 99mTc-pertechnetate) to the rectal mucosa. It consists of a two-channel plastic tube with one blunt rounded tip 132 and two-layer donut-type inflated balloon 140 fixed in the middle 5-cm portion of the tube. A 0.2-mm flexible plastic tube is placed between the balloon walls and serves to deliver a small volume of radioactive tracer (for instance 50 μL) through an opening 144 in a balloon surface 142 to the intestinal mucosa. Several delivery channels can be created to allow multiple, site- specific tracer delivery to the intestinal mucosa surface. The sites of the tracer delivery can be studied with single or multi-channel radiometers, gamma-camera techniques, PET scan or MRI dynamic imaging for rapid evaluation of mucosal absorption function. With modification in size this disposable delivery system 100 allows accurate and site-specific delivery of the tracer to almost all sites of the gastro-intestinal (GI) tract, upper airways, and the GU system. The delivery device 100 will be used for intracavitary site-specific delivery of radioactive tracer (for example 99mTc-pertechnetate) to the rectal mucosal surface. The delivery device 100 includes a two-channel plastic tube 120 with one blunt rounded tip 132 and a three-layer thin latex sleeve covering the middle 5-cm portion of the tube. One of the channels ends between the first and the second latex layers of the balloon 140 and serves as an air duct 210 to inflate this space to the shape of a donut-type balloon. A 0.2-mm flexible plastic tube serves as the delivery tube 330 and runs between the second layer, associated with the balloon 140, and the third latex layer 142 and ends right above a 1mm diameter opening 144 in the middle of the third outmost layer 142. In a flattened or deflated condition the surface of the delivery device is completely smooth, so there is no threat of mucosa damage upon insertion. When inflated, both the second layer, associated with the balloon 140, and third balloon layer 142 come into close contact with the intestinal walls, and the end 310 of the delivery tube 300 pops up in the middle of the balloon surface 142 through the expending opening 144 in the third outmost latex layer. A 0.2-mm flexible plastic tube 310 serves to deliver a small volume of radioactive tracer between the balloon 140 and intestinal surfaces. When released, the entire volume of tracer containing fluid (for instance 50 μL) spreads over the site of contact with mucosal (serosal) surface. Example 2: Detector and Delivery System For Delivering and Monitoring

Tracer Delivery to Rectal Mucosa The probe 132 will be used for intracavitary site-specific delivery of radioactive tracer (for example 99mTc-pertechnetate) to selected sites of GI tract (from mouth cavity to the rectum), respiratory tract, urogenital system, peritoneum and pleural cavities, and subsequent direct monitoring of the tracer absorption rate from the site of tracer's application. The delivery device includes either a scintillation-crystal 810 or a scintillation-fluid-based detection system 1000 mounted on the distal end 130 at the tip 132 of a flexible fiber optic cable 800. Balloon based tracer delivery assures accurate and site-specific delivery of a small amount of radioactive tracer to the absorptive surface. A standard photoelectric multiplier and registration equipment 820 is attached to the fiberoptic cable and is used to monitor radioactivity signals in a time-dependent fashion. The detection/delivery probe 100 can be made of various dimensions (for instance ranging from 1.0 mm to 20.0 mm diameter) to fit into a standard fiber optic scope operating channels. Thus the detection/delivery probe can be integrated with gastroscopes, colonoscopes, bronchoscopes, duodenoscopes, sigmoidoscopes, rhinolaringoscopes, nosopharingoscopes, ventriculoscopes, otoscopes, sinuscopes, cystoscopes, laparoscopes and arthroscopes in order to provide rapid and minimal invasive monitoring of absorption function from mucosal and serosal surfaces of GI respiratory and au tracts, joints, peritoneal and pleural cavities. Direct monitoring of radioactive tracer's absorption rate from the site of tracer's application will increase sensitivity of the detection system and provide more diagnostic information from a substantially smaller quantity of administered radioactivity. In addition, scintillation-fluid-based detection system 1000 can be used for contact monitoring of β-emitting tracers from outside or inside of the body. This increases the variety of radiopharmaceuticals used for the absorption study. The probe 100 will be used for contact site-specific delivery of radioactive tracer (for example 99mTc-pertechnetate) to selected sites of GI tract (from mouth cavity to the rectum), respiratory tract, urogenital system, skin, peritoneum and pleural cavities, and subsequent direct monitoring of the tracer absorption rate from the site of tracer's application. The probe 100 includes of a flexible fiber optic cable 800 coated with a two-layer wall latex balloon 140 at the distal end 132. A 0.1-mm flexible plastic tube runs between the balloon 140 walls and opens at the top of the balloon through an opening 144 in the second outmost layer 142 of the balloon 140 wall. In the deflated or flattened condition, the surface of the delivery device 100 is completely smooth (Figs. 6 and 7). The second plastic tube 210 ends under the first latex layer and serves to fill balloon 140 with scintillation fluid 1000, which covers the fiber optic cable 800 (FIGs 10 and 11). When filled with scintillation fluid 1000, the balloon 140 wall comes into direct contact with mucosal (serosal) surface, so a small volume of radioactive tracer (for instance 10 to 50 μL) can be released directly between balloon and mucosal ( or serosal) surface. When released, the entire volume of tracer containing fluid (for instance 10 to 50 μL) spreads over the site of contact with mucosal (serosal) surface. The detector/delivery probe 100 can be also made of a scintillating crystal 810 mounted on the tip of a flexible fiber optic cable 800 (FIGs. 8 and 9). The crystal 810 is coated with a two-layer wall latex balloon 140. A 0.1-mm flexible plastic delivery tube 300 is placed between the balloon walls 140, 142 and serves to deliver a small volume of radioactive tracer (for instance 10 to 50 μL) to the mucosal or serosal surfaces as described above. The second plastic tube ends under the balloon walls and serves as an air duct to inflate balloon. A standard photoelectric multiplier and monitoring equipment attached to the fiber-optic cable can be used to monitor radioactivity signals in a time-dependent fashion. The detector/delivery probe 100 can be made of various dimensions (for instance ranging from 1.0 mm to 20.0 mm diameter) to fit into a standard fiber optic scopes operating channels. Thus the detection delivery probes can be integrated with gastroscopes, colonoscopes, bronchoscopes, duodenoscopes, sigmoidoscopes, rhinolaringoscopes, nosopharingoscopes, ventriculoscopes, otoscopes, sinuscopes, cystoscopes, laparoscopes and arthroscopes in order to provide rapid and minimal invasive monitoring of absorption function from mucosal and serosal surfaces of GI respiratory and GU tracts, joints, peritoneal and pleural cavities.

Direct monitoring of radioactive tracer's absorption rate from the site of tracer's application will significantly increase sensitivity of the detection system and provide more diagnostic information from a substantially smaller quantity of administered radioactivity. In addition, the scintillation- fluid-based detection system 1000 can be used for contact monitoring of β-emitting tracers from outside or inside of the body. This increases the variety of radio pharmaceuticals used for the absorption study.

Conclusion

Advantageously, the delivery system is capable of delivering small amounts of fluids, such as drugs or radial protectors and radionuclides, to specific positions within a body while being held in place within a body as a drug or other treatment is delivered to a specific portion of the body. The delivery system can also be positioned near the area to which a drug or other fluid needs to be delivered. The delivery system can be easily and controllably released and removed after an appropriate dosage is delivered to the specific portion of the body. The amount of fluid passing through the drug delivery system. The rate at which the fluids can be delivered can also be determined, especially for radionuclides or radio protectors, delivered to a certain area of the body. The device can be used in a non invasive manner or can be inserted via an operating channel, such as an incision or portal in the body of the mammal. It is to be understood that the above description is intended to be illustrative, and not restrictive. Many other embodiments will be apparent to those of skill in the art upon reviewing the above description. The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.

Claims

What is claimed is:

1. A delivery system for delivering a substance to a body surface, said delivery system comprising: an elongated catheter having a proximal end and a distal end, the elongated catheter including a main body portion having at least two lumens extending from the proximal end to a position near the distal end; a first balloon portion positioned around the main body of the catheter near the distal end, the first balloon portion in fluid communication with at least one of the lumens in the catheter; a second balloon portion positioned over the first balloon portion, said second balloon portion having an aperture therein; and a delivery tube having a first end and a second end, one of the first end and the second end positioned near the proximal end of the catheter, the other of the first and second end positioned near the apeture in the second balloon portion.

2. The delivery system of claim 1 wherein a portion of the delivery tube is captured between the first balloon portion and the second balloon portion.

3. The delivery system of claim 1 wherein a first portion of the delivery tube passes through another of said lumens in the catheter and wherein a second portion of the fluid delivery tube is captured between the first balloon portion and the second balloon portion.

4. The delivery system of claim 1 wherein the one of the first end and the second end of the delivery tube is positioned near the proximal end and is adapted to couple with a syringe such that a selected amount of fluid can be passed through the delivery tube from the end near the proximal end to the end near the apeture in the second balloon portion.

5. The delivery system of claim 1 wherein the first balloon portion is inflated with a fluid to fix the position of the distal end of the catheter with respect to a body and to bring the fluid delivery tube into close proximity with the body.

6. The delivery system of claim 5 wherein the fluid used to inflate the first balloon portion is a gas.

7. The delivery system of claim 1 further comprising an optical cable passing through another of the lumens, the optical cable passing into the inflatable space associated with the first balloon portion, wherein the first balloon portion is inflated with a scintillation fluid and wherein the delivery tube is used to deliver a fluid including a radioactive component such that as the radioactive component decays the scintillation fluid produces a light incident, the light carried by the optic cable from the distal end to the proximal end of the catheter.

8. The delivery system of claim 7 further comprising: a photomultiplier attached to the fiber optic cable at the proximal end; a counter attached to the photomultiplier to count the number of incidents of light over time; and a processor for correlating the number of counts received by the counter to a rate of fluid flow through the fluid delivery tube.

9. The delivery system of claim 7 further comprising a light shifting device attached to the end of the optical cable passing into the inflatable space associated with the first balloon portion.

10. The delivery system of claim 1 further comprising; a fiber optical cable; and a scmtiallation crystal attached to one end of the fiber optical cable, the scintiallation crystal positioned in the inflatable space associated with the first balloon portion, wherein the delivery tube is used to deliver a fluid including a radioactive component such that as the radioactive component decays the scintillation crystal produces a light incident, the light carried by the optic cable from the distal end to the proximal end of the catheter.

11. The delivery system of claim 1 wherein the aperture in the second balloon portion is at the distal end of the catheter.

12. The delivery system of claim 1 wherein the aperture in the second balloon portion is near the distal end of the catheter.

13. An apparatus adapted to deliver a selected fluid to a surface within a body comprising a probe further comprising: a balloon including a first balloon end: a second balloon end; and an inner balloon portion; a dose delivery tube including: a first dose tube end; and a second dose tube end, said second dose tube end of said dose delivery tube extending through said balloon from said first balloon end to said second balloon end of the balloon; a fluid delivery tube including a first fluid delivery tube end; a second fluid delivery tube end; and an inner fluid delivery tube portion, said second fluid delivery tube end engaging the balloon, and inner fluid delivery tube portion of said fluid delivery tube and in fluid engagement with said inner balloon portion; and a fiber optic cable having a first end and a second end, said second end of said fiber optic cable being disposed within said inner balloon portion.

14. The apparatus of claim 13 further comprising a crystal connected to said second end of said fiber optic cable.

15. The apparatus of claim 13 further comprising a scintillation crystal connected to said second end of said fiber optic cable.

16. The apparatus of claim 15 wherein air is passed through the fluid delivery tube to inflate the balloon of the probe.

17. The apparatus of claim 13 further comprising a light shifting device connected to said second end of said fiber optic cable.

18. The apparatus of claim 15 wherein a scintillation fluid is passed through the fluid delivery tube to inflate the balloon of the probe.

19. The apparatus of claim 13 wherein the probe is used to assess the function integrity of a mucosal membrane

20. A probe for assessing the function integrity of a mucosal membrane, said probe comprising: a balloon having a first end and a second end, and an inner portion, said balloon being capable of containing a fluid; a tracer delivery tube having a first end and a second end, said second end of said tracer delivery tube extending through said balloon from said first end of said balloon to said second end of said balloon; a fluid delivery tube having a first and second end, and an inner portion, said second end of said fluid delivery tube engaging said balloon, and said inner portion of said fluid delivery tube being in fluid engagement with said inner portion of said balloon; and a fiber optic cable having a first end and a second end, said second end of said fiber optic cable being in contact with said fluid in said inner portion of said balloon.

21. A method for delivering a substance to a body surface, said method comprising the steps of: providing a delivery system capable of intracavitary operation; positioning said delivery system adjacent to said body surface; and deploying said delivery system adjacent to said body surface, whereby said substance is delivered to said body surface.

22. A method for assessing the functional integrity of a mucosal membrane, said method comprising the steps of: administering a reagent to said mucosal membrane; employing a dynamic scintigraphy to measure the absorption in said mucosal membrane of said reagent; and collecting data from said dynamic scintigraphy.

23. A kit including: a delivery system for delivering a substance to a body surface, said delivery system comprising: an elongated catheter having a proximal end and a distal end, the elongated catheter including a main body portion having at least two lumens extending from the proximal end to a position near the distal end; a first balloon portion positioned around the main body of the catheter near the distal end, the first balloon portion in fluid communication with at least one of the lumens in the catheter; a second balloon portion positioned over the first balloon portion, said second balloon portion having an aperture therein; and a delivery tube having a first end and a second end, one of the first end and the second end positioned near the proximal end of the catheter, the other of the first and second end positioned near the aperture in the second balloon portion; and a selected fluid to be delivered using the delivery system.

24. The kit of claim 23 further including information on use of the kit.

25. The kit of claim 23 further including a syringe adapted to attach to the delivery tube of the delivery system.