KR100802010B1 - Tc-99m Nano Tin Colloid and Preparation Thereof - Google Patents

Abstract

The present invention relates to a technetium tin nanocolloid and a manufacturing method thereof. In particular, the present invention relates to a technetium tin nanocolloid obtained by mixing a radioactive technetium or a solution of a compound thereof with a solution containing tin or a compound thereof, sodium or a compound thereof, poloxamer and polyvinylpyrrolidone, and an easy manufacturing method thereof.

According to the present invention, the technetium tin nanocolloid of the present invention can be produced very easily as nano-sized particles that can facilitate the communication of the lymphatic system, and can be prepared uniformly by appropriately adjusting the size of the armpit lymph nodes, such as breast cancer It can be used as a nuclear medicine radiopharmaceutical that is very useful as a radiotracer for finding surveillance lymph nodes.

Technetium, Tin Colloid, Surveillance Lymph Node, PVP

Description

Technetium tin nanocolloid and its manufacturing method {Tc-99m Nano Tin Colloid and Preparation Thereof}

1 is a photograph of the last form of the technetium tin nanocolloids contained in the Bayer according to an embodiment of the present invention;

2 is a size distribution diagram of technetium tin nanocolloid particles prepared according to an embodiment of the present invention;

3 is a field emission scanning electron micrograph (FE-SEM) of the technetium tin nanocolloid according to an embodiment of the present invention;

4 is an FE-SEM photograph of a technetium tin nanocolloid ( ^99m Tc-SNPPPT-50) according to an embodiment of the present invention;

Figure 5 is a graph showing the cell intake of ^99m Tc-SNPPPT-30 and ^99m Tc-SNPPBT-50 in macrophages according to an embodiment of the present invention;

6 is a gamma image for confirming the distribution in vivo when intravenous injection of technetium tin nanocolloids in accordance with an embodiment of the present invention;

7 is a static gamma image obtained after 30 minutes of dynamic imaging by injecting a technetium tin nanocolloid according to an embodiment of the present invention into the subcutaneous tissue of the right and left sides of the rabbit hind paw, respectively; And

FIG. 8 is a graph showing the results of FIG. 7 in coefficient / pixel ratio over time of lymph nodes. FIG.

The present invention relates to a technetium tin nanocolloid and a manufacturing method thereof. In particular, it is a nano-sized particle that can facilitate the communication of the lymphatic system, and can be manufactured very easily, and the size can also be manufactured uniformly by adjusting the size of the lymphatic system, which is very useful as a radiotracer for finding a lymph node such as axillary lymph node of breast cancer. It relates to a technetium tin that can be used as a radiopharmaceutical and an easy manufacturing method thereof.

Tin colloids, which are used in imaging nuclear medicine, can reach several micrometers in size and are predated in the liver cells of Kupffer cells and are mainly used to obtain liver images. The preparation of this tin colloid is known to be very simple.

Colloids that use mechanisms ingested mainly by macrophages vary in their colloid distribution. Tin colloids are several micrometers long, so they are taken from Cooper cells, which are evenly distributed in the liver. Smaller cases are known to be captured by macrophages in the spleen and bone marrow. The most relevant factors in the distribution of colloids in vivo are particle size and hydrophilicity.

Nuclear medical tests using colloids have also been widely used to detect the lymphatic system and to detect sentinel lymph nodes. If the particle size is more than 500 nm, radiopharmaceuticals injected into the epilepsy will not be transported to the lymphatic system but will remain at the site of injection. Particle sizes below 5 nm are absorbed through the capillaries rather than the lymphatic system and therefore do not accumulate in the monitoring lymph nodes. The ideal particle size for obtaining lymphatic nuclear medicine images is 10-30 nm.

Radiopharmaceuticals that have been used to obtain lymphatic images up to now include ^99m Tc-HSA, ^99m Tc-antimony sulfur colloid and ^99m Tc-filtered sulfur colloid. These are summarized in Table 1 below by particle size characteristics.

Colloid size ^99m Tc-antimony sulfide 3-12 nm ^99m Tc-HSA 4 nm Filtration ^99m Tc-colloidal albumin 50-200 nm Filtration ^99m Tc-Sulfur Colloid <200 nm ^99m Tc-Tin Colloid (Heptate) 260-3900 nm

Sentinel lymph nodes are lymph nodes that are first drained from the tumor in order for cancer cells to migrate through the lymph system in order to metastasize through the lymphatic system. The significance of this lymph node is that there is no need for extensive lymph node resection if the histology reveals no cancer cells in the lymph nodes. In other words, since cancer cells are less likely to metastasize through the lymphatic system, it is possible to apply a surgical method to remove only cancer masses, so that the patient's postoperative recovery can be faster, quality of life can be improved, and postoperative side effects can be minimized. Efforts to find a monitored lymph node are being made before the procedure.

The most widely used method of finding a lymph node is the method of injecting radiopharmaceuticals around a mass and confirming the movement of the lymph nodes through the lymph system to the lymph nodes. In addition, there is a method of injecting the dye and finding the lymph nodes in the operating room, but the disadvantage is that it is difficult to find the lymph nodes because the dye is spread to the surrounding tissue or lymph nodes over time.

Recently, in performing breast resection in breast cancer patients, a surgical method for finding a monitored lymph node to confirm metastasis and confirming the extent of surgery has been widely recognized. For this purpose, it is very important to find the monitoring lymph nodes around the tumor. If the detection of lymph nodes in the operating room can be done by using a gamma ray detector regardless of the time after topical injection by nuclear medicine method, it is possible to provide the surgeon with a stable surgical procedure. will be. Because colloids and albumin have mobility to the upper part, it requires very limited time to find the surveillance lymph node by incision around the lesion at the operating room after topical injection. This was one of the reasons that the method has been used on a limited basis. The root cause was that the particle size used was inadequate and uneven.

The most important thing to note about finding a monitored lymph node is that the drug used should not travel through the upper lymphatic vessel after arriving at the lymph node. Because if the medicine moves over time, cancer cells will not be able to find the first lymph node to meet. At this time, the mechanism by which the drug is used in the lymph nodes is the most widely used mechanism for phagocytic macrophages in the lymph nodes. Therefore, the most important thing is to use a medicine of a size that can be used well for phagocytosis by macrophages.

To date, 10-30 nm particles are known to be the best size for finding lymph nodes. Therefore, if a suitable particle size can be produced by an easy method, a more efficient treatment strategy can be devised to find a lymph node before surgery and to determine whether cancer cells have metastasized and then to decide on a treatment plan for the patient.

Accordingly, the present invention is not only excellent in vivo stability and bioavailability using nuclear medicine methods, but also suitable for obtaining lymphatic nuclear medicine images, and uniform nanoparticle-sized technetium tin useful for detecting surveillance lymph nodes such as tumors. An object of the present invention is to provide a nanocolloid and an easy manufacturing method thereof.

In order to achieve the above technical problem, the present invention relates to a technetium tin nanocolloid obtained by mixing radioactive technetium or a solution of a compound thereof with a solution containing tin or a compound thereof, sodium or a compound thereof, poloxamer and polyvinylpyrrolidone to provide.

In addition, the present invention comprises the steps of preparing a first solution containing tin or a compound thereof, sodium or a compound thereof, poloxamer and polyvinylpyrrolidone; And it provides a method for producing a technetium tin nanocolloid comprising the step of mixing a radioactive technetium or a second solution of the compound to the first solution.

Hereinafter, the present invention will be described in detail.

The technetium tin nanocolloids of the present invention can be smoothly communicated in the lymphatic system using polyvinyl pyrrolidone (polyPVP) and have a particle size of nano units ideal for finding surveillance lymph nodes such as tumors. It is a nuclear medicine radiopharmaceutical.

In the present invention, the tin compound has a general formula of SnX ₂ as a divalent tin solution, X may be used to select one or more selected from the halogen element, acetate, sulfate, oxalate and succinate, but only limited to these It doesn't happen.

In the present invention, the sodium compound has a general formula of NaX ', X' may be a halogen element, but is not limited thereto.

In the present invention, the polyvinylpyrrolidone (poly (vinyl pyrrolidone); PVP) is used to control the particle size of the colloid is a water-soluble tertiary amide, has a strong Lewis base, and also has good biocompatibility Refers to a polymer with). The PVP is generally applied as a suspension stabilizer of oral or topically administered drugs in drug formulations. In the present invention, it was confirmed through the examples that the PVP serves as a good stabilizer of tin colloid. Specific examples of the polyvinylpyrrolidone include N-vinylpyrrolidone, N-vinyl-5-methyl-2-pyrrolidone, and the like, but are not limited thereto.

In the present invention, the poloxamer has almost no toxicity to the human body and has a property of reversibly sol-gel transition by heat, and thus can be used as a sustained release drug delivery material. Crosslinking efficiency can be increased, and also serves as a polymer surfactant, and refers to a terpolymer composed of poly (ethylene oxide) -poly (propylene oxide) -poly (ethylene oxide) as shown in the following formula (1).

Equation (1):

In formula, X, Y, Z is an integer and can be restrict | limited by the molecular weight of a poloxamer.

In such a solution containing tin or a compound thereof, sodium or a compound thereof, poloxamer and PVP, for example, radioactive technetium such as ^99m Tc, a technetium tin nanocolloid having a smooth size for lymphatic communication of the present invention can be formed. Can be. By properly blending the components listed above, the size of the colloidal particles can be adjusted in the range of 10 nm to 30 nm, preferably 15 nm to 30 nm. In this range, the lymphatic system can be smoothly communicated to facilitate monitoring lymph nodes. This is because it has a size suitable for searching and obtaining images. Too large a size may result in sedimentation, resulting in poor stability. Too small a size may be absorbed through the capillaries rather than the lymphatic system and thus not integrated into the lymph nodes.

However, since the pH of the mixed solution may be difficult to inject into animals including humans, a pH adjuster may be further added to the mixed solution to adjust the pH. By properly mixing the type of the pH adjuster it is possible to further control the size of the final colloid. The pH adjuster may be used, for example, phosphate buffer, sodium bicarbonate, and the like, but is not limited thereto.

According to an embodiment of the present invention, when the amount of PVP is properly adjusted and sodium bicarbonate is selected, it has a size of about 13 nm, which is the most suitable size for searching for monitoring lymph nodes and obtaining images. Observation under a microscope confirmed that a very uniform and round colloid was formed.

Technetium tin nanocolloids as described above, (a) preparing a first solution containing tin or a compound thereof, sodium or a compound thereof, poloxamer and polyvinylpyrrolidone; And (b) mixing a second solution of radioactive technetium or a compound thereof with the first solution.

Furthermore, (c) may further comprise the step of adding a pH adjuster to the mixture.

At this time, by properly mixing the amount of the polyvinylpyrrolidone (PVP) and the type of pH adjusting agent, it is possible to obtain the size of the final colloidal particles smooth in the lymphatic communication, the size can also be adjusted in various ways.

In step (a), tin or a compound thereof, sodium or a compound thereof, poloxamer and polyvinylpyrrolidone are combined in parts by weight of 1 to 2: 4 to 20: 2 to 10: 4 to 100, respectively to prepare a first solution. By manufacturing, it is possible to obtain the size and uniformity of the colloidal particles that are easy for lymphatic communication.

Furthermore, by measuring the size with the amount of tin or its compound, sodium or its compound and poloxamer fixed, and by varying the amount of PVP, a size of about 5 nm to about 15 nm nanoscale that can facilitate lymphatic communication can be achieved. In addition, the size was also sustained for a certain time was confirmed through the embodiment of the present invention is very stable.

In step (b), the second solution of the radiotechnetium or a compound thereof is mixed in an equivalent ratio of 1/5 to 1/15 with respect to the first solution of step (a).

In the presence of the first solution of step (a), ^{radiotechnetium} , such as ^99m Tc, is added at an equivalent ratio of about 1/5 to about 1/15 to form a radioactive complex. Rounded technetium tin nanocolloid complex having a uniform shape in the above range can be formed.

Optionally, step (c) is used to control the pH of the technetium tin nanocolloid complex to control the pH since the pH of the complex obtained in steps (a) to (b) may be difficult to inject into animals including the human body. It is carried out by adding a pH adjusting agent such as phosphate buffer solution, sodium bicarbonate and the like.

By adjusting the amount of the pH adjuster more appropriately, the colloidal particles of the desired size of the present invention can be obtained more uniformly. Accordingly, the preferred amount of the present invention is in the range of about 0.1 to about 1 equivalent ratio based on the complex obtained in step (b) for the phosphate buffer solution, and about 10 ^-12 to 10 ^-10 equivalent ratio for sodium bicarbonate. Range.

The technetium tin nanocolloid according to the present invention prepared as described above may be usefully used for finding a monitoring lymph node through topical injection around the tumor, using a gamma-ray detector at the operating room regardless of time after local injection. This can provide a stable surgical procedure.

Hereinafter, the technetium tin nanocolloid and a manufacturing method thereof according to the present invention will be described in detail. The following examples are only intended to illustrate the preferred best embodiment of the present invention is not limited or restricted to the following examples only.

<Examples 1-10> Technetium tin nanocolloid preparation

(1) material preparation

Tin tin chloride (SnCl ₂ ), sodium chloride (NaCl), tin fluoride (SnF ₂ ) and sodium fluoride (NaF) were purchased from Sigma-Aldrich Chemical Co. Poloxamer 188 and polyvinylpyrrolidone (PVP, Kollidon 30) were purchased from BASF, Korea. Technetium was eluted from the Technetium generator produced by Samyoung Unitech.

(2) Technetium tin nanocolloids ( ^99m Manufacture of Tc-Tin Colloid

1.25 mg of tin chloride (SnCl ₂ ), 10 mg of sodium chloride (NaCl), 5 mg of poloxamer, and 10-50 mg of PVP were weighed and prepared in a vacuum vial in order (Daiichi Radioisotope Laboratories, Ltd, Tokyo, Japan). In addition, 1.25 mg of tin fluoride (SnF ₂ ), 10 mg of sodium fluoride (NaF), 5 mg of poloxamer, and 10-50 mg of PVP were also prepared in a vacuum vial. The names of the samples used are abbreviated SNPPT for abbreviation respectively. ^99m Tc pertechnetate (1480-1850 MBq) was prepared in 5 mL of brine, mixed with the reagent, and the vial was shaken strongly by hand to form a technetium tin nanocolloid complex.

When manufacturing the technetium tin nanocolloid using tin chloride, the size of PVP was changed to 10 ~ 40 mg, and the size was 7 ~ 11 nm.However, after several hours, the white precipitate appeared and the size became very large. Esau was confirmed to fall. When PVP was not used, it was very large with a size of several micrometers. However, when prepared using 50 mg of PVP, the size was similar to about 10 nm even up to 24 hours.

When manufacturing the technetium tin nanocolloids using tin fluoride, the size of the PVP was changed from 0 to 50 mg, and the size was measured. The results are summarized in Table 2 below.

SnF ₂ NaF Poloxamer 188 Tc-99m Time polymer 30 minutes 90 mins 3 hours 6 hours PVP 10 mg 8.4 ± 6.41 4.0 ± 0.36 5.1 ± 1.65 15.3 ± 2.50 PVP 20 mg 9.43 ± 3.26 4.5 ± 0.40 5.6 ± 2.03 13.7 ± 4.57 PVP 30 mg 20.2 ± 1.76 5.7 ± 1.17 5.6 ± 1.97 10.9 ± 2.65 PVP 40 mg 23.4 ± 0.85 6.4 ± 1.72 7.2 ± 2.97 7.6 ± 0.61 PVP 50 mg 18.7 ± 4.27 9.6 ± 1.67 8.2 ± 1.25 10.1 ± 1.43

The nano-technetium tin nanocolloids prepared as described above had a pH of 5 or less which is difficult to inject in animals. To prepare the pH of the sample, 0.3 ml of phosphate buffer solution (0.1 M, pH 7.3) and 10 µl of sodium bicarbonate (10 mg / ml) were respectively added. The pH was checked using a pH paper after mixing the phosphate buffer solution and sodium bicarbonate in the prepared technetium tin nanocolloids.

The final form of the nanoparticle-sized technetium tin nanocolloid was photographed and shown in FIG. 1 . From FIG. 1 , it was confirmed that the manufactured technetium tin nanocolloid was colorless and transparent.

<Evaluation>

1. Size of particles

The size of the technetium tin nanocolloids prepared according to Examples 1 to 10 was measured using a particle size analyzer (Particle Size Analyzer UPA-150; Microtrac, USA) of Jeonbuk Research Institute, Korea. And summarized in Table 2. The measurement was repeated three times per sample and the sample preparation was n = 3. Here, the case of using a phosphate buffer solution was abbreviated as SNPPPT, and the case of using sodium bicarbonate was abbreviated as SNPPBT. The following figure shows PVP usage.

SnF ₂ NaF Poloxamer 188 Tc-99m PBS (SNPPPT) Time polymer 30 minutes 90 minutes 3 hours 6 hours PVP 10 mg 48.4 ± 5.12 46.8 ± 15.7 57.3 ± 6.53 64.4 ± 5.87 PVP 20 mg 16.5 ± 12.19 55.8 ± 5.31 50.6 ± 13.24 54.7 ± 2.66 PVP 30 mg 55.3 ± 37.59 139.0 ± 139.2 81.9 ± 41.6 75.4 ± 42 PVP 40 mg 25.0 ± 6.92 31.5 ± 6.24 46.37 ± 3.46 44.2 ± 4.41 PVP 50 mg 25.1 ± 8.02 30.6 ± 7.82 48.5 ± 0.36 102.5 ± 107.3

In Table 3, the 90 minute image size of SNPPPT-30 was 139.0 ± 139.2 for reference.

SnF ₂ NaF Poloxamer 188 Tc-99m Sodium Bicarbonate (SNPPBT) Time polymer 30 minutes 90 minutes 3 hours 6 hours PVP 10 mg 513.7 ± 107.82 551.3 ± 287.17 1369.4 ± 1121.62 1404 ± 1109 PVP 20 mg 9.27 ± 0.75 1157.3 ± 1344.9 968.58 ± 608.07 1195 ± 672.6 PVP 30 mg 8.97 ± 0.49 184.38 ± 231.56 1141 ± 1256.02 643.9 ± 685.61 PVP 40 mg 8.37 ± 1.25 17.8 ± 4.86 11.3 ± 2.12 10.2 ± 1.15 PVP 50 mg 7.6 ± 0.69 16.5 ± 6.76 12.7 ± 1.11 12.6 ± 1.04

In Table 4, the 90 minute image size of SNPPBT-50 was 16.5 ± 6.76 for reference.

Among them, size distribution diagrams of particles for SNPPT-30, SNPPT-50, SNPPPT-30, and SNPPBT-50 are shown in FIG. 2 .

As can be seen from Table 3, Table 4, and Figure 2 , when the phosphate buffer solution was added, the difference in time and the amount of PVP change did not show a large size from about 50 nm to 70 nm. On the other hand, when sodium bicarbonate was added, there was a big difference in time and PVP variation, and SNPPBT-40 and SNPPBT-50 showed a size of about 13 nm, similar to that without buffer solution.

2. Observation of Morphology and Size of Technetium Tin Nanocolloids by Electron Microscopy

FE-SEM analysis was performed to confirm the form of the prepared technetium tin nanocolloids. For the preparation of the analytical sample, an appropriate amount of the prepared technetium tin nanocolloid was diluted to 3-5 μl on a silicon wafer, and dried for about one day, and then coated with platinum (Pt) using E-1030 (Hitachi, Japan). The coating thickness is about 6 nm. The electron microscope was measured using a S-4700 scanning electron microscope (Hitachi, Japan) of the Jeonbuk Research Institute of Korea Basic Science.

3 is a FE-SEM electron micrograph of the technetium tin nanocolloids according to the present embodiment.

Only 50 mg of PVP was mixed in 5 ml of physiological saline as a control with the present Example, and this was measured by FE-SEM. In Figure 3 a and c are the results of observing "PVP-50 + brine" 200,000 times and 50,000 times, respectively. From a and c, it was confirmed that the rectangular shape, which is a characteristic form of the salt, was very uniformly distributed by PVP.

3b and 3d show that the technetium tin nanocolloid ( ^99m Tc-SNPPBT-50) prepared by mixing 50 mg of PVP and sodium bicarbonate was dropped on a silicon wafer, and then measured by FE-SEM. b and d are the results of observing " ^99m Tc-SNPPBT-50" at 200,000 times and 50,000 times, respectively. The size of the particles is indicated by b scale bars. The FE-SEM measurement result confirmed that the colloids having a round shape of approximately 13 nm size were formed, which is the same result as measured by the particle size analyzer. In addition, it can be seen that the overall appearance is very uniform.

On the other hand, as shown in Figure 4, in the case of technetium tin nanocolloid ( ^99m Tc-SNPPPT-50) prepared by mixing PVP 50 mg and phosphate buffer solution, FE-SEM observation showed a size of about 80 ~ 90 nm . In addition, unlike SNPPBT-50, most were not uniform.

3. In vitro experiment

Macrophage RAW 264.7 was purchased from Korea Cell Line Bank. 1 × 10 ^{6 were} dispensed into serum-free RPMI-1640 medium and cultured in a 37 ° C., 5% CO ₂ incubator. After confirming that the RAW 264.7 cells were stabilized overnight, serum-free RPMI-1640 was added, and ^99m Tc-SNPPPT-30 and ^99m Tc-SNPPBT-50 were treated for 20 minutes at concentrations of 0, 0.5, and 1 μl. After treatment, cells were detached using trypsin-EDTA, washed twice with 1 × PBS, and radioactivity was measured using a gamma counter (COBRA II, Packard). Radioactivity was calibrated by protein quantitation of each sample. The experiment was repeated three times.

Figure 5 shows the cell intake of ^99m Tc-SNPPPT-30 and ^99m Tc-SNPPBT-50 in macrophages. Comparing the cell intake of ^99m Tc-SNPPPT-30 and ^99m Tc-SNPPBT-50 in macrophages with reference to FIG. 5 , the small SNPPBT-50 showed approximately 2.1 times higher uptake at the same treatment concentration, The treatment concentrations increased by 2 times, respectively, about 2.7 times.

4. Gamma image and surveillance lymph node image

All animal experiments were conducted in accordance with the animal test regulations of Chonbuk National University Medical School Ethics Committee. Rats 6-7 weeks old (Orient-Bio, Seoul) and New Zealand white rabbits (2.5-3.0 kg, Hanil, Jeonju) were purchased and prepared a week before the experiment. Anesthetics were injected into the rabbit's ear vein using a mixture of ketamine and lumps. The rabbits were injected with ^99m Tc-SNPPPT-30 on the right and ^99m Tc-SNPPBT-50 on the left between the toes of the hind legs. The rabbits were secured by tying the forefoot and hind paws in a supine position, and the camera was used for ECAM (SIMENS Medical System Inc., Illinois, USA). After 30 minutes of 30 seconds of dynamic images, 40, 60, 160, 190, and 220 minutes of static images were obtained. Regions of Interest (ROI) were obtained from the obtained images as coefficient values, and both were compared and analyzed.

6 is treated with (A) ^99m Tc-SNPPPT-30, and (B) ^99m Tc-SNPPBT-50 7.4 MBq to confirm the distribution in vivo when intravenous injection of technetium tin nanocolloid according to the present embodiment Gamma image after 5 minutes of rats is shown. As a result, ^99m Tc-SNPPPT-30 mainly accumulated in the liver and showed bone marrow imaging. On the other hand, the small ^99m Tc-SNPPBT-50 showed bone marrow images and was rapidly discharged through the kidneys.

From this, it is confirmed that ^99m Tc-SNPPBT-50 is small enough to be captured by the bone marrow mononuclear phagocyte system (MPS), and also a particle sized to be partially discharged through the glomeruli. Can be.

7 will illustrating a static image obtained after 30 minutes dynamic image by scanning in the subcutaneous tissue of the right side and the left side of the rear foot rabbit a technetium-tin nano-colloid according to the present embodiment, respectively, Figure 8 is the coefficient according to the time of a result lymph node / It shows the pixel ratio. Subcutaneous tissues on the right and left sides of rabbit hind paw were injected with ^99m Tc-SNPPPT-30 and ^99m Tc-SNPPBT-50, respectively. Referring to FIGS . 7 and 8 , ^99m Tc-SNPPBT-50 having a size of about 13 nm showed a coefficient value in which radioactivity of a popliteal node lymph node gradually increased over time, while ^99m Tc In SNPPPT-30, it was observed that after the initial peak, it gradually decreased.

In the present examples and experiments, it was confirmed that PVP plays a role of a good stabilizer of technetium tin nanocolloids. In order to apply the manufactured technetium tin nanocolloids to a living body, the pH must be finally adjusted. However, the size of the colloid was also changed by the buffer solution, and it was also confirmed that the final colloid size could be variously adjusted by properly mixing the amount of PVP and the type of the buffer solution.

Among them, ^99m Tc-SNPPBT-50 was found to have the most suitable size for searching for lymph nodes and to obtain an image. It could be confirmed that the formation. In addition, it was confirmed through repeated experiments that colloids can be prepared with the same size under the same conditions, and about 15 to about 30 nm of them are actually particles that macrophages can ingest well. Proved through.

In summary, nanoscale colloids can be prepared very easily using tin and PVP. The colloids have a very uniform particle size and average 13 nm. Cell experiments showed that ^99m Tc-SNPPBT-50 could induce colloidal uptake by macrophages higher than ^99m Tc-SNPPPT-30.

The use of technetium tin nanocolloids to detect surveillance lymph nodes through gamma-ray detectors in tumor patients is expected to provide accurate monitoring of lymph nodes. In addition, the surgeon can be usefully used to proceed with the surgery regardless of time. Moreover, it is thought that ^99m Tc-SNPPPT-30 can be used to obtain liver images by being captured in Cooper cells with a size of 100 nm or less.

As described above, the technetium tin nanocolloid according to the present invention is not only water soluble and excellent in biocompatibility, but also easily manufactured as nano-sized particles which can facilitate communication of the lymphatic system, and the size thereof is also appropriately It can be used as a nuclear medicine radiopharmaceutical that is very useful as a radiotracer to find surveillance lymph nodes such as axillary lymph nodes of breast cancer.

Claims (13)

Technetium tin obtained by mixing a radiotechnetium compound solution with a tin compound, a sodium compound, a terpolymer copolymer composed of poly (ethylene oxide) -poly (propylene oxide) -poly (ethylene oxide) and a solution containing polyvinylpyrrolidone Nanocolloids. The technetium tin nanocolloid of claim 1, wherein the technetium tin nanocolloid solution further includes a pH adjuster including a phosphate buffer solution and sodium bicarbonate. The technetium tin ^nanocolloid of claim 1, wherein the radioactive technetium is ^99m Tc. The tin compound of claim 1, wherein the tin compound has a general formula of SnX ₂ as a divalent tin solution, and X is one or more selected from halogen elements, acetates, sulfates, oxalates, and succinates. . The technetium tin nanocolloid of claim 1, wherein the particle size of the technetium tin nanocolloid is in a range of 10 nm to 30 nm. The technetium tin nanocolloid according to claim 1, wherein the sodium compound has a general formula of NaX ', and X' is one of halogen elements. Preparing a tertiary copolymer compound consisting of a tin compound, a sodium compound, a poly (ethylene oxide) -poly (propylene oxide) -poly (ethylene oxide), and a first solution containing polyvinylpyrrolidone; And mixing a second solution of radioactive technetium or a compound thereof with the first solution. The method of claim 7, further comprising adding a pH adjuster to the mixed solution of the first solution and the second solution. The method of claim 8, wherein the pH adjuster is a phosphate buffer solution or sodium bicarbonate. The polyvinyl copolymer compound according to any one of claims 7 to 9, wherein the first solution is composed of a tin compound, a sodium compound, a poly (ethylene oxide) -poly (propylene oxide) -poly (ethylene oxide) and a polyvinyl copolymer compound. Pyrrolidone is a method for producing a technetium tin nanocolloids are contained in a weight ratio of 1 to 2: 4 to 20: 2 to 10: 4 to 100, respectively. The method of claim 7, wherein the second solution is mixed in an equivalent ratio of 1/5 to 1/15 with respect to the first solution. A technetium tin nanocolloid for detecting tumor monitoring lymph nodes according to any one of claims 1 to 6. A technetium tin nanocolloid for tumor surveillance lymph node search prepared according to claim 7.

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