Preparation and Biodistribution of Re-188-Sulfur Colloid Suspension in Lipiodol / 대한핵의학회잡지

PURPOSE: Lipiodol is used for targeting liver cancers by administrating through the hepatic artery. In the present study, feasibility of Re-188-sulfur colloid suspension in lipiodol as a liver cancer targeting agent was investigated. MATERIALS AND METHODS: Re-188-sulfur colloid was prepared, harvested by centrifugation, washed with organic solvent and then suspended into lipiodol. Biodistribution of Re-188-sulfur colloid in normal saline and its suspension in lipiodol in mice after 1 hr of injection through the tail vein were investigated. Biodistribution and autoradiography of tumor-bearing liver was acquired after 5 min post-injection into left ventricle of the tumor-inoculated rats. RESULTS: After 1 hr of injection with Re-188-sulfur colloid suspensiob in lipiodol through the tail vein in normal mice (n=3), the uptakes in the liver and lung were 5.2+/-0.7 and 91.0+/-1.7% ID/organ, respectively. After 5 min of injection with Re-188-sulfur colloid suspention in lipiodol through the left ventricle in the tumor-inoculated rats (n=4), uptakes in the normal liver, hepatoma, and lung were 0.41+/-0.28, 1.88+/-1.57, and 1.65+/-1.54% ID/organ, respectively. And autoradiography of hepatoma showed increased uptake than normal liver tissues. CONCLUSION: Re-188-sulfur colloid suspension in lipiodol injected through the artery shows higher uptake in the hepatoma than normal liver tissue that indicates the feasibility as a new radiopharmaceutical for therapy of hepatoma.

Effect of Carrier on Labeling and Biodistribution of Re-188-Hydroxyethylidene diphosphonate / 대한핵의학회잡지

PURPOSE: Re-188-Hydroxyethylidene diphosphonate (HEDP) is a new cost-effective agent for systemic radioisotope therapy of metastatic bone pain. We investigated the influence of carrier for labeling and biodistribution of Re-188-HEDP using HEDP kit with or without carrier (KReO4). MATERALS AND METHODS: The kits (HEDP 15 mg, gentisic acid 4 mg and SnCl2.2H2O 4.5 mg) with or without carrier (KReO4 0.1 mg) were labeled with Re-188 solution, made available from an in-house generator by boiling for 15 min. We compared the labeling efficiency and stability of carrier-added and carrier-free preparations of Re-188-HEDP. Biodistribution and imaging studies of each preparation were performed in ICR mice (1.85~3.7 MBq/0.1 ml) and SD rats (74.1~85.2 MBq/0.5 ml). RESULTS: The carrier-added preparation showed high labeling efficiency (95% at pH 5) and high stability in serum (88%, 3 hr). However, the carrier-free preparation showed low labeling efficiency (59% at pH 5) and low stability (43%, 3 hr). The carrier-added preparation showed high uptake in bone and low uptake in stomach and kidneys. However, the carrier-free preparation showed lower uptake in bone and higher uptake in both stomach and kidneys, which is supposed to be due to released perrhenate. The carrier-added preparation also showed better images with higher skeletal accumulation, lower uptake in other organs and lower soft tissue uptake than the carrier-free preparation. CONCLUSION: The results of these studies clearly demonstrate that addition of carrier perrhenate is required for high labeling efficiency, stability, bone uptake and good image quality of Re-188-HEDP.

Dosimetry and MIRD for Re-188 Liquid Balloons / 대한핵의학회잡지

Re-188 is suitable for endovascular liquid-balloon brachytherapy for the prevention of restenosis after angioplasty. Re-188 was concentrated to 3700 MBq/ml and labeled with DTPA. According to dosimetric calculation, it took 420 seconds using Re-188 solution with concentration of 3700 MBq/ml to irradiate 17.6 Gy to the target at 1 mm from the balloon surface. Software was made to estimate the irradiation time. MIRD calculation with dynamic bladder model yielded the whole body dose of Re-188-DTPA as 0.005mGy/MBq in case of balloon rupture and release of the whole amount into the blood.

Intracoronary Radiation Therapy Using Re-188 after percutaneous Coronary Angioplasty / 대한핵의학회잡지

Percutaneous coronary angioplasty is well established therapeutic modality in the management of coronary artery disease. However, the high restenosis rate of 30 to 50% limits its usefulness. The principal mechanism of restenosis, ntimalhyperplasia, is the proliferative response of vessel wall to injury, which consists largely of smooth muscle cells. A large body of animal investigations and a limited number of clinical studies have established the ability of ionizing radiation to reduce neointimal proliferation and restenosis rate significantly. Human studies have been reported that intravascular radiation after first restenosis inhibits a second restenosis. Encouraged by these reports, we are also conducting a double blind, placebo-controlled, randomized trial to evaluate this new therapeutic modality in patients with coronary artery stenosis. The objective of our trial is to determine the safety and efficacy of catheter-based solutional beta emitting radioisotope system in preventing restenosis after angioplasty. This review describes the vascular brachytherapy systems and isotopes that have been utilized in the initial clinical trials performed in this area of post PTCA coronary restenosis. The results of many worldwide ongoing clinical trials will determine whether this new technology will change the future practice of vascular intervention.

Dosimetry and Medical Internal Radiation Dose of Re-188-DTPA for Endovascular Balloon Brachytherapy Against Restenosis after Coronary Angioplasty / 대한핵의학회잡지

PURPOSE: Liquid beta emitter filled in angioplasty balloon could be used to perform endovascular balloon brachytherapy to prevent coronary artery restenosis. We investigated the dosimetry for Re-188-DTPA liquid-filled balloon and medical internal radiation dosimetry in case of balloon leakage. MATERIALS AND METHODS: We estimated radiation dose from an angioplasty balloon (20 mm lengfh, 3 mm diameter cylinder) to the adjacent vessel wall using Monte Carlo EGS4 code. We obtained time-activity curves of kidneys in normal dog and calculated Tmax, T1/2. Using MIRDOSE3 program, we estimated absorbed doses to the major organs (kidneys, bladder) and the whole body when we assumed that balloon leaked all the isotope contained. RESULTS: The radiation dose was 17.5 Gy at the balloon surface when we applied 3,700 MBq/ml of Re-188 for 100 seconds. Fifty percent of the energy deposited within 1 mm from the balloon surface. The estimated internal dose to the whole body was 0.005 mGy/MBq and 18.5 mGy for the spillage of 3,700 MBq of Re-188. CONCLUSION: We suggest that Re-188-DTPA can be used for endovascular balloon brachytherapy to inhibit coronary artery restenosis after angioplasty with tolerable whole body radiation dose in case of balloon rupture.

Production of Re-188 / 대한핵의학회잡지

188Re (beta=22 MeV; gamma=155 keV; T1/2=16.9 hours) is an attractive therapeutic radioisotope which is produced from decay of reactor-produced tungsten-188 parent (T1/2=69 days). 188W has been produced from the double neutron capture reaction of 186W. 188Re can be easily obtained by elution of saline on alumina based 186W/188Re generator, which is commercially available. Complexes labelled with 188Re have been developed for the radiotherapy treatment of diseases because of the desirable nuclear properties of the radioisotope and it's chemical properties similar to those of technetium, a well established diagnostic agent.

Labelling with Rhenium-188 / 대한핵의학회잡지

There is considerable interest in 188Re due to its favorable properties as a therapeutic radionuclide. 188Re and 99mTc act as a matched pair because of their similar chemical properties, and therefore methods of labeling with 99mTc can be applied to the labeling with 188Re. With appropriately chosen agents as carriers of 188Re, the labeling can be readily carried out using 188ReO4- in the presence of a reducing agent. 188Re radio pharmaceuticals based on 99mTc complexes have been synthesized and are currently being studied for clinical use. Some of them are shown to be suitable for therapeutic use and promising for radiotherapy in nuclear medicine.

In Vitro Properties and Biodistribution of Tc-99m and Re-188 Labeled Monoclonal Antibody CEA79.4 / 대한핵의학회잡지

PURPOSE: Radiolabeled CEA79.4 antibody has a possibility to be used in radioimmunoscintigraphy or radioimmunotheraphy of cancer. We investigated the in vitro properties and biodistribution of CEA79.4 antibody labeled with Re-188 or Tc-99m. MATERIALS AND METHODS: CEA79.4 was reduced by 2-mercaptoethanol to produce-SH reside, and was labeled with Re-188 or Tc-99m. For direct labeling of Tc-99m, methylene-diphosphonate was used as transchelating agent. CEA79.4 in 50 mM Acetate Buffered Saline (ABS, pH 5.3) was labeled with Re-188, using stannous tartrate as reducing agent. In order to measure immunoreactivity and the affinity constant of radiolabeled antibody, cell binding assay and Scatchard analysis using human colon cancer cells SNU-C4, were performed. Biodistribution study of labeled CEA79.4 was carried out at 1, 14 and 24 hr in ICR mice. RESULTS:. Labeling efficiencies of Tc-99m and Re-188 labeled antibodies were 92.4+/-5.9% and 84.7+/-4.6%, respectively. In vitro stability of Tc-99m-CEA79.4 in human serum was higher than Re-188-CEA79.4. Immunoreactivity and affinity constant of Tc-99m-CEA79.4 were 59.2% and 6.59x109 M-1, respectively, while those of Re-188-CEA79.4 were 41.6% and 4.2x109 M-1, respectively. After 24 hr of administrations of Re-188 and Tc-99m labeled antibody, the remaining antibody, the remaining antibodies in blood were 6.32 and 9.35% ID/g respectively. The biodistribution of each labeled antibody in other organs was similar because they did not accumulate in non-targeted organs. CONCLUSION: In vitro properties and biodistribution of Re-188-CEA79.4 were similar to those of Tc-99m-CEA79.4. It appears that Re-188-CEA79.4 can be used as a suitable agent for radioimmunotherapy.

Quality Control of Tungsten-188/Rhenium-188 Generator / 대한핵의학회잡지

PURPOSE: For the purpose of using Re-188 as a therapeutic radionuclide, we performed the quality control of the W-188/Re-188 generation system. MATERIALS AND METHODS: Several quality control tests of the Re-188 eluate from generator were carried out of about 300 days. After elution of Re-188 with normal saline (20 ml), chromatogram and gamma-ray spectrum of Re-188 eluate were obtained. The presence of aluminum which was derived from the elumina bed of the generator was detected by using aluminum ion indicator kit. Re-188 eluate was allowed to decay for several days, and then W-188 breakthrough in the Re-188 eluate was measured by detecting gamma-ray at 227 keV and 290 keV. The pH and the pyrogenicity of the eluate were checked. The Re-188 eluate from the generator was 67.4+/-7.0% of W-188 during 270 days, and it was hightest at third day after previous elution. Radiochemical purity of Re-188 eluate obtained from chromatogram was higher than 99%. Gamma-ray spectrum of Re-188 eluate showed a peak at 155 keV. Aluminum ion and W-188 contamination were not detected. The pH of Re-188 eluate was 3 and the concentration yield was 85%. CONCLUSION: Our experiments and results on quality control tests of Re-188 eluate from W-188/Re-188 generator may be useful for setting W-188/Re-188 generator in hospitals.

Quality Control of Tungsten-188/Rhenium-188 Generator / 대한핵의학회잡지

PURPOSE: For the purpose of using Re-188 as a therapeutic radionuclide, we performed the quality control of the W-188/Re-188 generation system. MATERIALS AND METHODS: Several quality control tests of the Re-188 eluate from generator were carried out of about 300 days. After elution of Re-188 with normal saline (20 ml), chromatogram and gamma-ray spectrum of Re-188 eluate were obtained. The presence of aluminum which was derived from the elumina bed of the generator was detected by using aluminum ion indicator kit. Re-188 eluate was allowed to decay for several days, and then W-188 breakthrough in the Re-188 eluate was measured by detecting gamma-ray at 227 keV and 290 keV. The pH and the pyrogenicity of the eluate were checked. The Re-188 eluate from the generator was 67.4+/-7.0% of W-188 during 270 days, and it was hightest at third day after previous elution. Radiochemical purity of Re-188 eluate obtained from chromatogram was higher than 99%. Gamma-ray spectrum of Re-188 eluate showed a peak at 155 keV. Aluminum ion and W-188 contamination were not detected. The pH of Re-188 eluate was 3 and the concentration yield was 85%. CONCLUSION: Our experiments and results on quality control tests of Re-188 eluate from W-188/Re-188 generator may be useful for setting W-188/Re-188 generator in hospitals.

Preparation and Biodistribution of Re-188 Sulfru Colloid / 대한핵의학회잡지

PURPOSE: We evaluated the usefulness of Re-188 sulfur colloid for radiation synovectomy and therapy of intraperitoneal metastasis. MATERIALS AND METHODS: We investigated the labeling efficiency of Re-188 sulfur colloid on various conditions. The stability of Re-188 sulfur colloid was observed at room temperature for 24 h and in human serum and synovial fluid for 72 h. The particle size distribution of Re-188 sulfur colloid was rneasured by filtering with various pore size filters. Animal experiment was performed in mice and rabbits. RESULTS: The labeling efficiency of Re-188 sulfur colloid was 64,5+/-5.8% (n=5) at the conditions of sodium thiosulfate 40 mg, EDTA Na2.2H2O 0,8 mg, KReO4 0.8 mg at pH l. After purification, the radiochemical purity was higher than 99%. The stability of Re-188 sulfur colloid was high (>99%) at room temperature for 24 h and in human serum and synovial fluid for 72 h. The particle size distribution of Re-188 sulfur colloid was 0.3% (10 micrometer). In mice, 1 h postinjection of Re-188 sulfur colloid into tail vein, uptakes in lung, liver and muscle were 37.30+/-5.36, 32.33+/-5.79, 6.60+/-0.02% 1D/organ respectively. After I.p. injection in rnice, the uptakes of extraperitonial organs of Re-188 sulfur colloid at 1 and 24 h were 0.1+/-0.1, 0.4+/-0.1% ID/organ, and the excretions through urine and feces (~70 h) were low (2.68+/-0.80, 0.95+/-0.17%). When Re-188 sulfur colloid was injected to synovial space of rabbit, the uptake in other organs except knee was very low. CONCLUSION: Re-188 sulfur colloid showed high labeling efficiency, stability and potency for clinical use.

Labeling and Biodistribution of Re-188-DTPA ( Diethylenetriaminepentaacetic acid ) / 대한핵의학회잡지

Re-188 is useful candidate for therapeutic radionuclide because it has a physical half life of 17 hours, contains beta ernissions suitable for therapy(maximum energy 2.12MeV) and emits a garnma ray that is suitable for quantitative diagnostic scanning(155keV). To use He-188 as a radionuclide compound of angioplasty balloon radiotherapy, we investigated the labelling method and biodistribution of Re-188- DTPA. We postulated that labeled Re-188-DTPA is preferable because it would be excreted via urinary system more easily than other compounds. To label Re-188 with DTI'A, 1ml of 222MBqI(6mCi) of Re-188 was added to DTPA solution(DTPA 20mg, SnC4 2HsO 10mg, pH 3.5) and boiled at 100C for 120min in water bath. pH was adjuted to 5 with 2.3Fo sodium acetate. I.abeling efficiency was measured using TLC-SG(acetone, saline). We evaluated biodistribution of Re-188-DTPA in sacrificed mice at 10 and 60 minutes after injection. We acquired images of kidneys, and drew tirne-activity r.urves in normal dogs and rats and calculated Trnax and Tl/2 in rats. The labelling efficiency was 95.7Yo on average. Labelling of Re-188-DTPA was stable(90% after 5hours) in vitro at room temperature. According to time-activity curves of dogs and rats, it took 15 to 20 minutes after injection for Re-188-DTPA to be washed out through kidneys. In conclusion, Re-188-DTPA was successfully labeled, Re-188-DTPA was stable in vitro and was excreted early via kidneys in animals. We could recornmend Re-188-DTPA as radionuclide of potential use in angioplasty balloon radiotherapy.