CN1238991A - Sol preparation of rhenium nuclein labeled iodinated oil and its preparing process and application - Google Patents
Sol preparation of rhenium nuclein labeled iodinated oil and its preparing process and application Download PDFInfo
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Abstract
A sol preparation of rhenium nuclein labeled iodinated oil is a lyophilic one prepared from rhenium nuclein labeled sol particles and iodinated oil through ultrasonic treatment, and features high stability and safety and low toxic by-effect. It can concentrate the radioactivity in heptic cancer region with T/NT value up to (10-14) : 1, so it can be used as the medicine for radiotherapy of liver cancer and positioning display of cancer. It can be directly used for hepatic arteria injection for treating liver cancer, especially the later-phase liver cancer.
Description
The present invention relates to the field of radiopharmaceutical and nuclear medicine,, can be used as hepatocarcinoma body radioactivity medicine especially about sol preparation of rhenium nuclein labeled iodinated oil, preparation method and application thereof.
Primary hepatocarcinoma is the modal malignant neoplasm of China, and annual have 100,000 new patients approximately, can the radical excision case during prescription on individual diagnosis 10-20% only, and the patient of 80-90% can only take to appease Sex therapy according to the state of an illness.In order to save patient, utilize radionuclide to carry out internal radiation and kill and wound treatment, to be accepted by increasing nuclear medicine clinician, the great advantage of comparing the body radioactivity medicine with chemotherapy, radiotherapy is that curative effect is certain, toxic and side effects is little.
The eighties radioactivity in mid-term interventional therapy becomes the liver cancer treatment focus gradually, as the radiosiotope carrier, comes labeled iodinated oil optionally to be trapped in for a long time in the liver tumor district blood capillary with iodine-131 iodized oil, plays the thromboembolism effect.Utilizing the β ray to kill and wound cancerous cell has certain curative effect, prolongs survival period (Kobayashi Het al., Acta Radiol Diangn, 1986, the 27:139 of hepatocarcinoma patient; Park C Hetal., Clin Nucl Med, 1986,11:514; Raoul J L et al., J Radiol, 1986,67:797; Xerox China etc., Chinese tumor magazine, 1995,17 (1): 20-22), but the shortcoming of iodine-131 is long half time (8 days), energy of height (364keV), and radioiodine easily is shed to other internal organs in vivo, and heavier to patient and medical worker's radiation damage.
The early 1990s is used emission high pure beta ray 90Y nucleic (2.27MeV) instead, its half-life is short to be 64h, be more suitable for treatment than iodine-131, but because 90Y deposits in skeletal system easily, destroy problems such as bone marrow, limited it at clinical use (SHYH-JEN WANG et al., Appl Radiat Isot, 1996,47 (3): 267-271; Bayouth J.E.et al., Med Phys, 20:1089).In recent years, because the superior particularity of rhenium-186 and rhenium-188 nucleic, rhenium obtains very big attention as the radiation treatment medicine in medical science, rhenium-the 186th, reactor is produced nucleic, half-life is 91h, the beta-particle ceiling capacity is 1.076MeV, and energy of is 137keV, and maximum range is 5.0mm in the tissue.Rhenium-188 is the daughter of parent tungsten-188, and the half-life is 17h, and the beta-particle ceiling capacity is 2.12MeV, and energy of is 155keV, and maximum range is 12mm in the tissue.Rhenium-188 is fit to remote transportation as the generator nucleic, and is easy to use.But because of the rhenium-188 half-life shorter, beta-particle energy height, imaging results are again not as good as rhenium-186, so select for use rhenium-186 nucleic as the more suitable (list of references: Guozheng LIU, Liu Baili, the radiopharmaceutic present state and perspectives of rhenium of treatment, isotope, 1995,8 (1): 53).
In order to reduce damage to normal structure, raising is to the concentration of liver tumor, radionuclide is connected on tumoraffin monoclonal antibody and the fragment exempts from medicine as putting, this also is one of radiopharmaceutical and nuclear medicine studies focus in the world, existing article report rhenium nucleic connects the lung cancer therapy (list of references: Beaumier P.L.Venkatesan P.et al. that is used for the people by part and monoclonal antibody, Cancer Research, 1991,51:676-681).Because the specificity of hepatocarcinoma monoclonal antibody, Mus source property and enter the tumor locus amount and wait problem does not very little still have at present the report of this respect.
Once reported (list of references: Venkatesan P.P.et al., Nucl MedBiol, 1990,17 (4): 357-362) utilize abroad
186Re-sulfuration rhenium soliquid, treatment rheumatoid arthritis and synovitis, also there is the formal product supply in French CIS company.But we test and find single sulfuration rhenium labelling soliquid Drug therapy hepatocarcinoma of using, radioactivity is easily disperseed to be adsorbed on whole hepatic tissue and is denied that Schwann Cells engulfs by Ke, and very fast metabolism is distributed to other internal organs, cause normal structure is killed and wounded, and can not be trapped in the purpose that the liver tumor position reaches the treatment tumor.
Therefore, combining with iodized oil and form colloidal sol with the rhenium nucleic isotope labeling colloidal solid that serves as a mark, and be applied to the research work of liver cancer treatment, is to have very much scientific meaning and practical value.
The object of the invention provides a kind of sol preparation of rhenium nuclein labeled iodinated oil, and it is the lyophilic sol preparation of being made by rhenium nuclein labeled colloidal solid and iodized oil.
Another object of the present invention provides the preparation method of sol preparation of rhenium nuclein labeled iodinated oil, and this solution is to be made by ultrasonic echography by rhenium nuclein labeled colloidal solid and iodized oil.
Another object of the present invention provides the application of sol preparation of rhenium nuclein labeled iodinated oil, and it can be used as the treatment of hepatocarcinoma body radioactivity and tumor is positioned the medicine of video picture.
Sol preparation of rhenium nuclein labeled iodinated oil of the present invention, preparation method and application thereof, be that mainly it will launch strong β ray, the weak gamma-ray rhenium nucleic of emission is made the colloidal solid of labelling again, then marking particle is evenly wrapped with ultrasound wave and in the iodized oil medium, formed the iodized oil lyophilic sol, the hepatocarcinoma patient hepatic artery interventional therapy can be directly used in, and video picture can be positioned.
Sol preparation of rhenium nuclein labeled iodinated oil of the present invention is meant
186Re or
188Re labeled iodinated oil sol preparation, both are same at sol preparation of the present invention, preparation method and in using, therefore below with
186Re labeled iodinated oil sol preparation is that example is described in detail.
The invention provides
186Re labeled iodinated oil sol preparation, its characteristic is as follows:
State: oily colloidal solution
Color: sepia
PH value: 6-8
A colloid degree: all be suitable for from the nanometer to the micron order, best granularity is 10-50nm 5-10%, 50-100nm 60-80%, 100-300nm 15-30%
Radiochemicsl purity:＞95%
Uclear purity:＞95%
Sterility test: no antibacterial and fungus growth
Endotoxin is checked:＜0.25Eu/mol
Acute toxinology experiment: LD
50Be 26.47ml/Kg
Storage-stable: after 4 ℃-37 ℃ one weeks of placement, radiochemicsl purity still＞95%.
The present invention
186The preparation method of Re labeled iodinated oil sol preparation:
The synthetic route sketch map is referring to Fig. 1, and getting mol ratio is 1: ammonium perrhenate and the sodium thiosulfate of 30-100 are mixed with aqueous solution, and the requirement by the colloidal sol radioactive intensity adds a certain amount of NH again
4 186ReO
4Solution (by reactor industy production); heating is 5 minutes in the boiling water bath; (volume ratio of the former with the latter is 5: 0.2-2) to add concentrated hydrochloric acid solution by above-mentioned cumulative volume amount; reactant liquor is by the yellowish sepia that changes into; and continue reacting by heating after 10-30 minute; cooling; the centrifugal supernatant that removes; add the centrifugal repetition secondary of water washing; regulate PH to 6-8 with NaOH solution; the centrifugal supernatant that removes; wash the centrifugal supernatant that removes again with water, obtain the rhenium nuclein labeled rhenium sulfide colloid particle of sepia, after dewatering; be mixed into the oily colloid that flows with iodized oil and colloidal solid; both optimal proportions are that every milliliter of iodized oil contains colloidal solid 1-10mg, are not bonded on the reactor, promptly until not sedimentation of colloidal solid with ultrasonic echography
186Re labeled iodinated oil sol preparation, putting productive rate are 84-92%, after testing radiochemicsl purity＞95%.
The present invention
186Re labeled iodinated oil sol preparation is measured every performance as follows:
(1)
186The radiochemicsl purity of Re labeled iodinated oil sol preparation detects
The good iodized oil sol preparation product of labelling with No. 1 paper of Xinhua (2.5 * 12mm) drip micro-examples analyses radiological measuring as ply of paper, and developing solvent is a normal saline,
186Re labeled iodinated oil sol preparation product is at initial point, and dissociates
186ReO
4 -R
fBe about 0.7, the every batch of product radiochemicsl purity all＞95% (see figure 2).
(2)
186The colloidal solid degree size measurement of Re labeled iodinated oil sol preparation
The good iodized oil sol preparation sample dispersion of labelling adopts under the nearly physiological situation of atomic force microscope (AFM) and measures on mica sheet, records the following (see figure 3) of best particle diameter size distribution:
10-50nm?????5-10％
50-100nm????60-80％
100-300nm????15-30％
(3)
186Re labeled iodinated oil sol preparation radionuclide power spectrum and absolute intensity are measured
Adopt the HPGe Gmx detector and the PC-CAMAC multi-parameter data acquisition system of ORTEC company, with the gamma-rays method rhenium radioactive source and product are carried out nuclear spectrum and strength detection, energy calibration and absolute efficiency scale all adopt
152Eu standard source (see figure 4), according to
186The feature gamma-rays main peak of Re is 137keV, calculates reactor and produces NH
4 186ReO
4Solution is uclear purity＞95% after the 4th day,
186The iodized oil sol preparation uclear purity of Re labelling all＞95% (seeing Fig. 5,6).
(1)
186Re labeled iodinated oil sol preparation vitro stability detects
186Re labeled iodinated oil sol preparation vitro stability is to detect by external serum culture experiment, good iodized oil sol preparation adding 1ml human serum stirs mixed to get the 1ml labelling, cultivated balance phase-splitting taking-up upper serum liquid survey free radioactivity 48 hours in 37 ℃
186The radioactive intensity of Re, the calculating radioactivity is free only to account for 0.6% of overall strength to serum, illustrates that label is stable, does not have free
186The Re radioactivity comes off.
After 4 ℃-37 ℃ one weeks of placement, analyse detection with ply of paper, radiochemicsl purity is still＞95%.This shows that this colloidal sol has good storage root of Dahurian angelica stability.
(2)
186The acute toxicity test of Re labeled iodinated oil sol preparation
Adopt about Kunming mouse (male and female have concurrently) body weight 20g an abdominal channels shot
186Re labeled iodinated oil sol preparation is observed mice and is produced toxic reaction, and measures its half lethal dose.Each dosage group there is no tangible poison immediately and has paid effect behind the abdominal cavity single-dose, its LD
50Be 26.47ml/Kg.
Characteristic of the present invention is to utilize iodized oil can optionally accumulate in the liver tumor and the long period is trapped in the interior characteristic of tumor blood capillary, rhenium nuclein labeled rhenium sulfide colloid particle is evenly wrapped by in iodized oil by ultrasound wave, generate the outside the pale of civilization shell of solvent and strong bonded, form lyophilic sol, can inject liver tumor by the direct trans-hepatic artery of conduit, radioactivity is concentrated entirely in tumor locus, and kill and wound cancerous cell, very little to the normal cell radiation injury.
The present invention
186The therapeutic test in animal body of Re labeled iodinated oil sol preparation
Shorter because of primary hepatocarcinoma rat life span, and life span further shortens after opening the capable hepatic artery catheterization of abdomen, so should not observe
186The therapeutic effect of Re labeled iodinated oil sol preparation.For understanding sol preparation of the present invention whether therapeutic effect is arranged in animal body, select lotus human primary liver cancer nude mice model (list of references: Ma Cengchen etc. for use, China's tumor magazine, 1985,7:405) get the BaLB/C nude mouse, at the swollen human primary liver cancer's cell suspension of flank portion notch graft, treat that tumor is long to 0.8cm
3During the left and right sides, inject respectively
186Re labeled iodinated oil sol preparation (
186RL),
186Re labelling sulfuration rhenium colloid (
186Re
2S
7), iodized oil (L) and four groups of normal saline, every group is that four tumor bearing nude mices are treated, and observes that the tumor bearing nude mice gross tumor volume changes, tumor bearing nude mice life cycle and organs and tissues learn,
186The every Mus of Re labeled iodinated oil sol preparation is injected 37MBq/100 μ l, and obvious therapeutic effect is arranged, and the tumor suppression degree is apparently higher than other three groups (see Table 1 and table 2).
The present invention
186Re labeled iodinated oil sol preparation is the test of video picture locating effect in human body
For understanding
186Can Re labeled iodinated oil sol preparation dense poly-at the hepatocarcinoma specificity after injecting human body, do not influencing under the conventional therapy prerequisite, select two routine volunteers to test, patients clinical is diagnosed as primary hepatocarcinoma, huge, iconography determines to undergo surgery excision, and it is 740MBq that patient injects mean dose by Hepatic artery
186Re labeled iodinated oil sol preparation is 15ml altogether, carrying out ECT (single photon emission computerized tomography,SPECT) after injection in 24,48,72,96 hours checks, and the radioactivity of measuring hepatocarcinoma district, normal liver tissue and other internal organs is dense poly-, observe that video picture is the most clear during at 48 hours, radioactivity concentrates in the liver tumor place entirely in 96 hours as patient, all do not have obvious radioactivity in other each internal organs, the painstaking effort pond and gather, T/NT (liver tumor/liver normal structure) is than reaching 10-14: 1.
The present invention
186Re labeled iodinated oil sol preparation is to the test of hepatocarcinoma patient therapeutic effect
Select two examples can't operative treatment patient volunteer, be respectively 1665 at the Hepatic artery implantation dosage, 1850MBq
186Re labeled iodinated oil sol preparation 15ml dynamic observes liver tumor size variation and AFP content, before and after injection patient is made ultrasound diagnosis, CT examination and invention Peripheral blood examination and this sol preparation of clinical observation and pays the effect size to patient's poison.No significant change before and after the treatment of observed result peripheral blood, second week of AFP treatment back is worked the decline of carrying out property, two patients rose in injection and see that promptly borderline tumor is clear in back 15 days, echo strengthens, no increase tendency carried out CT examination on the 45th day, the result show with treatment before compare, lump all dwindles more than 1/3, and patient is also survival after half a year.Clinical observation result shows, the present invention
186Re labeled iodinated oil sol preparation pays effect little, safe in utilization, instant effect to patient's poison.
Confirm the present invention by video picture test in above-mentioned animal experiment, the human body and hepatocarcinoma patient therapeutic test
186Re labeled iodinated oil sol preparation is can radioactivity in the liver tumor district dense poly-, kills and wounds cancerous cell, and the inhibition of lump is had good effect, and then radiation injury is very little to normal cell and other internal organs, so the present invention
186Re labeled iodinated oil sol preparation can be applicable to position the medicine of video picture as hepatocarcinoma body radioactivity treatment and to tumor, can be directly used in the hepatocarcinoma patient hepatic artery interventional therapy, the advanced liver cancer patient's that can't excise of being particularly useful for performing the operation treatment.
Advantage of the present invention: sol preparation of rhenium nuclein labeled iodinated oil of the present invention is the lyophilic sol preparation of being made by rhenium nuclein labeled colloidal solid and iodized oil, therefore can sedimentation, storage stability is good, in 4 ℃-37 ℃ place a week after, radiochemicsl purity is still＞95%; It is little, safe and reliable that poison is paid effect; Confirm through animal experiment and human trial, sol preparation of rhenium nuclein labeled iodinated oil of the present invention is dense poly-in liver tumor district energy radioactivity, the T/NT value reaches 10-14: 1, so sol preparation is very little to normal cell and other internal organs radiation injury, can directly be positioned the liver tumor position, both can be used for the video picture location, can be used for treatment again, strong to cancerous cell lethality, CT examination confirms, treated back 45 days, lump dwindles more than 1/3 before treating; And cancerous cell is by strong β irridiation injury, not influenced by cancerous cell internalization rate as the colloidal sol of medicinal application, therefore effect directly, instant effect; The preparation method of sol preparation of the present invention is easy, quick again, cost is low, has very big economic effect and practical value.
The present invention is further elaborated by following drawings and Examples, but does not limit the scope of the invention.
Description of drawings:
Fig. 1 is
186Re labeled iodinated oil sol preparation synthetic route sketch map.
Fig. 2 is
186Re labeled iodinated oil sol preparation ply of paper is analysed the radiochemicsl purity spectrogram.
Fig. 3 is
186The colloidal particle diameter size distribution figure of Re labeled iodinated oil sol preparation.
Fig. 4 is
186Re labeled iodinated oil sol preparation radioactive nucleus absolute intensity is measured the efficiency calibration curve of the 20%HPGe detector of usefulness
(
152Eu does standard source, spacing 8cm).
Fig. 5 is NH
4 186ReO
4The solution reaction heap is produced the 4th day uclear purity can spectrogram.
Fig. 6 is
186Re labeled iodinated oil sol preparation uclear purity can spectrogram.
Fig. 7 is a lotus people hepatocarcinoma nude mice warp
186Re labeled iodinated oil sol preparation treatment back tumor cell metamorphosis figure.
On: after the treatment; Down: contrast.
Fig. 8 is case 1 hepatocarcinoma lump location CT scan figure.
Fig. 9 is case 1 liver tumor district filling defect technetium-99 scintigram.
Figure 10 is that case 1 liver A radiography (DSA) shows tumor staining figure.
Figure 11 is that case 1 Hepatic artery injects
186Re labeled iodinated oil sol preparation is the dense poly-figure of ECT scanning hepatocarcinoma position radioactivity after 48 hours.
Figure 12 is that case 1 Hepatic artery injects
186Re labeled iodinated oil sol preparation is ECT scanning after 48 hours, and the white line scope is ECT region of interest (RIO)
On: under the local picture: full-length picture.
Figure 13 is that case 2 Hepatic arterys inject
186Re labeled iodinated oil sol preparation is the dense poly-figure of ECT scanning hepatocarcinoma position radioactivity after 48 hours.
Figure 14 is that case 2 Hepatic arterys inject
186Re labeled iodinated oil sol preparation is the dense poly-figure of ECT scanning hepatocarcinoma position radioactivity after 72 hours.
Figure 15 is
186Patient's hepatocarcinoma size variation figure before and after the treatment of Re labeled iodinated oil sol preparation
On: under the preceding CT scan figure of treatment: inject CT scan figure after 45 days.
In the 15ml reaction tube, add 15mg NH
4ReO
4With 1.4g Na
2S
2O
3Be dissolved in the 1ml water, add 5.25 * 10 then
2MBq/ml NH
4 186ReO
4Radioactive solution 9ml; heating is after 5 minutes in the boiling water bath; add the 2ml concentrated hydrochloric acid fast, vigorous stirring, reaction is sepia by yellowish transformation; and continue reacting by heating after 10 minutes; taking-up is put into psychrolusia and is cooled off, the centrifugal supernatant that removes, and it is centrifugal to add the water washing of the 5ml left and right sides; wash again centrifugal repeat once after; regulate PH to 8 with the 1N sodium hydroxide solution, the centrifugal supernatant that removes adds the centrifugal supernatant that removes of 5ml left and right sides water washing again; obtain the sepia colloidal solid; after dewatering, with iodized oil in the 10mg/ml ratio by ultrasonic echography and colloidal solid mixing, until not sedimentation of colloidal solid; be not bonded on the reaction tube, promptly
186Re labeled iodinated oil sol preparation is got trace and is dripped that (2.5 * 12mm) launch with normal saline, survey increased radioactivity, and calculating radiochemicsl purity is 99%, and surveying the radioactivity total activity is 3.97 * 10 in No. 1 paper of Xinhua
3MBq, putting productive rate are 84%.Marked product granularity size is determined as with the AFM method
10-50nm??????7.14
50-100nm?????71.43
100-300nm????21.43。
In the 10ml reaction tube, add 5mg NH
4ReO
4With 140mg Na
2S
2O
3Be dissolved in the 500 μ l water, add 3.14 * 10 then
3MBq/ml NH
4 186ReO
4Radioactive solution 300 μ l; it is 5ml that water is adjusted to the reaction tube cumulative volume; heating is 5 minutes in the boiling water bath; add concentrated hydrochloric acid 2ml then fast; vigorous stirring; reactant liquor is sepia by yellowish transformation, and continues reacting by heating after 20 minutes, and taking-up is put into psychrolusia and cooled off; the centrifugal supernatant that removes; it is centrifugal to add the water washing of the 5ml left and right sides, wash again centrifugal repeat once after, regulate PH to 7.2 with the 1N sodium hydroxide solution; the centrifugal supernatant that removes; add the centrifugal supernatant that removes of 5ml left and right sides water washing again, obtain the sepia colloidal solid, after dewatering; with iodized oil in the 5mg/ml ratio by ultrasonic echography and colloidal solid mixing; until not sedimentation of colloidal solid, be not bonded on the reaction tube, promptly
186Re labeled iodinated oil sol preparation.Get trace and drip that (2.5 * 12mm) launch with normal saline, survey increased radioactivity, and calculating radiochemicsl purity is 98%, and recording the radioactivity total activity is 8.68 * 10 in No. 1 paper of Xinhua
2MBq, putting productive rate are 92%.
In the 10ml reaction tube, add 5mg NH
4ReO
4With 300mg Na
2S
2O
3Be dissolved in the 500 μ l water, add 3.14 * 10 then
3MBq/ml NH
4 186ReO
4Radioactive solution 800 μ l; it is 5ml that water is adjusted to the reaction tube cumulative volume; heating is 5 minutes in the boiling water bath; add concentrated hydrochloric acid 200 μ l then fast; vigorous stirring; reactant liquor is sepia by yellowish transformation, and continues reacting by heating after 30 minutes, and taking-up is put into psychrolusia and cooled off; the centrifugal supernatant that removes; it is centrifugal to add the water washing of the 5ml left and right sides, wash again centrifugal repeat once after, regulate PH to 6 with the 1N sodium hydroxide solution; the centrifugal supernatant that removes; add the centrifugal supernatant that removes of 5ml left and right sides water washing again, obtain the sepia colloidal solid, after dewatering; with iodized oil in the 1mg/ml ratio by ultrasonic echography and colloidal solid mixing; until not sedimentation of colloidal solid, be not bonded on the reaction tube, promptly
186Re labeled iodinated oil sol preparation is got trace and is dripped that (2.5 * 12mm) launch to survey increased radioactivity with normal saline, and calculating radiochemicsl purity is 96%, and recording the radioactivity total activity is 3.22 * 10 in No. 1 paper of Xinhua
3MBq, putting productive rate are 85%.
Embodiment 4
186Re labeled iodinated oil sol preparation is the therapeutic test observation of curative effect in animal body
Get the BaLB/C nude mouse,, treat that tumor is long to 0.8cm at the subcutaneous vaccination human primary liver cancer of flank portion cell suspension
3During the left and right sides, according to the form below 1 dosage experimentizes, and observes growth of tumor situation and life span.
Table 1 lotus tumor nude mouse internal therapy test implantation dosage
| Grouping | Injected material | Dosage | Volume | Approach |
| ????G 1 | ?? *186RL | ???37MBq | ????100μl | In the tumor |
| ????G 2 | ?? 186Re 2S 7 | ???37MBq | ????100μl | In the tumor |
| ????G 3 | ?? **L | ????0 | ????100μl | In the tumor |
| ????G 4 | Normal saline | ????0 | ????100μl | In the tumor |
Annotate: 1,
* 186RL is
186Re labeled iodinated oil sol preparation;
*L is an iodized oil
2, tumor bearing nude mice is divided into four groups, G
1, G
2, G
3, G
4Select four nude mices for use for every group.
Observed result
The dynamic observing of ㈠ gross tumor volume (seeing Table 2): inject in back 4 days, each organizes the gross tumor volume no significant difference, plays G on the 5th day
1, G
2The group tumor growth begins slowly, illustrates that tumor growth is suppressed, the 12nd day G
1The tumor volume of group is significantly less than other groups, in addition compares tumor with matched group and also has and dwindle for two groups, dwindles degree G
1＞G
3
Respectively organize tumor size variation (cm after table 2 treatment
3)
| The treatment natural law | ??????G 1 | ??????G 2 | ??????G 3 | ??????G 4 |
| ????0 | ??0.82±0.11 | ??0.79±0.04 | ??0.91±0.08 | ??0.84±0.15 |
| ????4 | ??0.85±0.11 | ??0.79±0.28 | ??1.41±0.07 | ??1.25±0.13 |
| ????5 | ??0.91±0.18 | ??1.24±0.44 | ??2.80±0.92 | ??3.26±1.49 |
| ????12 | ??1.33±0.85 | ??3.56±1.87 | ??4.42±0.25 | ??5.90±0.20 |
㈡ mice with tumor life span: G
1Group obviously prolongs.Mean survival time G
1Organize 60 days, G
2Organize 47 days, G
3Organize 31 days, G
4Organize 28 days.
The ㈢ organs and tissues is learned: four treated animals are not seen visceral organ injuries such as the heart, liver, lung, kidney under light microscopic, and tumor tissues is gangrenosum acne and changes, and cellularity is unclear, and endochylema is bitten acid enhancing, karyopycnosis (see figure 7).
For understanding
186Can Re labeled iodinated oil sol preparation dense poly-at the hepatocarcinoma specificity after injecting human body, selects hepatocarcinoma patient 2 examples, is the male, clinical diagnosis is a primary hepatocarcinoma, huge, iconography determines to undergo surgery excision, has accepted this test under the prerequisite that does not influence conventional therapy.
Administrated method: 2 each implantation dosage of routine patient are 740 MBq
186Re labeled iodinated oil sol preparation 15ml is by Seldingers (list of references Yamada R.et al., Radiology, 1983,148:397) method row Hepatic artery is put pipe, under the x-ray fluoroscopy hydrosol preparation is injected, and 24,48,72,96 hours capable ECT check after injection.
Developing method: according to the capable anteroposterior position of knub position, postero-anterior position, whole body γ video picture, image is provided with the region of interest of certain pixel size after machine is handled as calculated, measures the radioactivity ratio (T/NT) of cancer district and normal liver tissue and other internal organs.
Observed result:
24 hours capable ECT mensuration saw that a large amount of radioactivity are dense poly-in the lump after ㈠ injected sol preparation, and is obvious with the surrounding tissue boundary, has minute quantity to gather in the hepatic tissue, "dead" recording in the painstaking effort pond.Video picture is the most clear after the 48th hour, and liver and painstaking effort pond do not have obviously and gather T/NT value 10-14: 1, and after this gross activity reduces, and whole body reached background level with the nucleic decay in the 96th hour, but the cancer district still has more radioactivity dense poly-(seeing Fig. 8-14).
The the 1st, 2,3 month capable CT examination behind the ㈡ injection sol preparation, tumor area still has iodized oil to gather.
Above presentation of results, iodized oil can be incited somebody to action as carrier
186Re brings cancerous tissue into, and is evenly distributed in cancerous tissue, and character is also more stable.
For understanding
186Whether Re labeled iodinated oil sol preparation has the effect of killing and wounding cancerous cell after entering human body, selects 2 routine patients to carry out preliminary clinical efficacy of medicine observing.
Clinical data: volunteer's 2 examples, be the male, case 1 is 43 years old, lump is positioned at right lobe of liver.With portal vein tumor thrombus, AFP＞10000ng/ml.Case 2 is 48 years old, and lump is positioned at liver middle period, AFP1800ng/ml.
Method: two cases are without the conventional chemotherapy medicine, and every example is put pipe through Seldinger ' s method, injects in Hepatic artery
186Re labeled iodinated oil sol preparation 15ml contains radioactivity 1480 MBq, 1665MBq respectively, dynamic observes the tumor size, and every 7 heaven-made ultrasound diagnosis, the 45th day capable CT examination surveyed AFP, liver function, a complete set of biochemical, peripheral hemogram per 2 weeks in the injection back.
Observed result:
㈠ safety: slightly feel uncomfortable in chest during injection, the epigastrium slight fever, (this phenomenon also occurs when conventional interventional therapy sensation of fullness, be the effect of contrast agent and iodized oil), the injection back was played the feel bitter taste on the 2nd day, weak, inappetence, but there is not vomiting, alleviated in about 5-7 days, played the sense dull pain in liver on the 3rd day, the companion continues low grade fever, indometacin can be alleviated, be that the important organ functional check showed that its toxic reaction is in WHO (list of references WHO (1979) Handbook for reporting results of cancertreatment offset publication due to neoplasm necrosis absorbed, No.48 WHO Genera) Gui Ding 0-2 inter-stage, peripheral blood and the preceding no significant change (seeing Table 3) of treatment.
Routine blood test detects before and after the treatment of table 3 hepatocarcinoma patient
| Routine blood test detects | | | ||
| Before the treatment | After the treatment | Before the treatment | After the treatment | |
| WBC(×10 9/L) RBC(×10 12/L) PLT(×10 9/L) | ?????3.64 ?????3.78 ?????86 | ????3.55 ????3.64 ????79 | ????4.12 ????3.98 ????64 | ?????3.97 ?????4.08 ?????61 |
The clinical general curative effect of ㈡: treatment rose about two weeks of back, and the conscious mental status is good, and appetite is improved, and food back feeling of repletion alleviates, and after this tumor is dwindled, and above symptom further takes a turn for the better.
㈢ AFP detects: the 2nd week of treatment back is played the decline of carrying out property of AFP, but does not drop to negative levels, and case 1 drops to＜400ng/ml after 45 days, and case 2 drops to 460ng/ml.
The ㈣ B ultrasonic detects: after the injection, B ultrasonic detects and shows that lump dwindles gradually, and B ultrasonic records the lump size and sees Table 4.
The super hepatocarcinoma patient treatment front and back lump size (cm that detects of table 4B
2)
| Before the injection | After the injection | |||||||
| The 15th day | The 21st day | The 28th day | 35 days | The 45th day | The 61st day | The | ||
| Case | ||||||||
| 1 | ??9.0×12 | ??9.0×10 | ?8.6×9.3 | ?8.0×8.5 | ?6.5×7.9 | ?5.0×7.0 | ??4.3×5.0 | |
| | ??8.0×9.0 | ??8.2×8.8 | ?7.5×8.3 | ?6.8×7.0 | ?6.0×6.5 | ?5.5×6.0 | ??3.0×5.5 | |
㈤ CT examination tumor minification: 2 patients rose after injection and see that promptly borderline tumor is clear on the 15th day, and echo strengthens, no increase tendency, the 45th day capable CT examination, with treat before all dwindle more than 1/3 than lump.Case 1 narrows down to 5cm * 7cm (seeing Figure 15) from 9cm * 12cm, and case 2 is contracted to 5.5cm * 6cm from 8cm * 9cm.
Claims (6)
1. a sol preparation of rhenium nuclein labeled iodinated oil is characterized in that it is the lyophilic sol preparation of being made by rhenium nuclein labeled colloidal solid and iodized oil, and the granularity of described colloidal solid is from the nanometer to the micron order.
2. sol preparation of rhenium nuclein labeled iodinated oil as claimed in claim 1 is characterized in that described rhenium nuclein labeled colloidal solid is
186Re or
186The colloidal solid of Re labelling.
3. sol preparation of rhenium nuclein labeled iodinated oil as claimed in claim 1 is characterized in that the granularity of wherein rhenium nuclein labeled colloidal solid is:
10-50nm??????5-10％
50-100nm?????60-80％
100-300nm????15-30％。
4. the preparation method of a sol preparation of rhenium nuclein labeled iodinated oil is characterized in that passing through NH
4ReO
4, Na
2S
2O
3, rhenium nuclein labeled ReO
4With HCL reaction, NH
4ReO
4And Na
2S
2O
3Mol ratio be 1: 30-100, NH
4ReO
4, Na
2S
2O
3With rhenium nuclein labeled ReO
4 -Overall solution volume and concentrated hydrochloric acid volume ratio are 5: 0.2-2; in the boiling water bath reacting by heating 10-30 minute; get rhenium nuclein labeled colloidal solid; be mixed into the oily colloid that flows with iodized oil and colloidal solid; with ultrasonic echography until not sedimentation of colloidal solid; be not bonded on the reactor, promptly get sol preparation of rhenium nuclein labeled iodinated oil.
5. the application of sol preparation of rhenium nuclein labeled iodinated oil as claimed in claim 4 is characterized in that described iodized oil and colloidal solid ratio are that every milliliter of iodized oil contains colloidal solid 1-10mg.
6. the application of sol preparation of rhenium nuclein labeled iodinated oil as claimed in claim 1 is characterized in that it can be used as the treatment of hepatocarcinoma body radioactivity and reaches the medicine that tumor is positioned video picture.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN99113705A CN1075389C (en) | 1999-05-14 | 1999-05-14 | Sol preparation of rhenium nuclein labeled iodinated oil and its preparing process and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN99113705A CN1075389C (en) | 1999-05-14 | 1999-05-14 | Sol preparation of rhenium nuclein labeled iodinated oil and its preparing process and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1238991A true CN1238991A (en) | 1999-12-22 |
| CN1075389C CN1075389C (en) | 2001-11-28 |
Family
ID=5276866
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99113705A Expired - Fee Related CN1075389C (en) | 1999-05-14 | 1999-05-14 | Sol preparation of rhenium nuclein labeled iodinated oil and its preparing process and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1075389C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1330635C (en) * | 2004-04-07 | 2007-08-08 | 中国工程物理研究院核物理与化学研究所 | Radioactive rhenium-N-accessory ingredient of alkyl dinitrogen disulfide for curing liver cancer and preparation method |
| CN110168669A (en) * | 2016-10-10 | 2019-08-23 | 肿瘤贝塔股份有限公司 | The preparation of RE-188/186 particle |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW319773B (en) * | 1996-02-06 | 1997-11-11 | Inst Of Nuclear Energy Atomic Energy Council | The novel preparation of Re-188 lipiodol |
-
1999
- 1999-05-14 CN CN99113705A patent/CN1075389C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1330635C (en) * | 2004-04-07 | 2007-08-08 | 中国工程物理研究院核物理与化学研究所 | Radioactive rhenium-N-accessory ingredient of alkyl dinitrogen disulfide for curing liver cancer and preparation method |
| CN110168669A (en) * | 2016-10-10 | 2019-08-23 | 肿瘤贝塔股份有限公司 | The preparation of RE-188/186 particle |
| CN110168669B (en) * | 2016-10-10 | 2023-10-27 | 肿瘤贝塔股份有限公司 | Preparation of RE-188/186 particles |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1075389C (en) | 2001-11-28 |
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