BACKGROUND: New stent implantation during intracoronary brachytherapy is discouraged due to the high risk of late thrombosis. However, new stent implantation is inevitable in some cases due to the inadequate ballooning or major dissections. Long-term follow-up results of newly implanted stents during brachytherapy are not well-known. We performed this study to evaluate the long-term clinical outcomes of newly implanted stents during intracoronary brachytherapy. METHODS: In the Seoul national university Post-Angioplasty RhEnium irradiation (SPARE) trial, patients were treated with conventional catheter-based technique and then randomized to either beta- radiation (RG) or control group (CG). Radiation was performed with 188 -rhenium-filled conventional balloon catheter system. From 1999 to 2001, new stent implantation was performed in 58 and 56 patients in RG and CG, respectively. Clinical and angiographic follow up data were analyzed. RESULTS: In RG, short-term angiographic restenosis rate was lower than CG (28.6% vs 53%, p=0.03). In RG, late thrombosis was found in 3 patients. However, there was no late thrombosis in CG. Two year major cardiac event rates were not different between the 2 groups (RG: 25.9% vs CG: 28.3%). Independent predictors for major cardiac event in RG were major dissections (>or=type C) after stent implantation (beta=70, p=0.01) and longer administration of dual antiplatelets (aspirin+clopidogrel/ ticlopidine, >6 months, beta=0.07, p=0.04). CONCLUSION: Stenting during intracoronary brachytherapy seems to be ineffective in reducing long-term event rates. When new stent implantation is inevitable during brachytherapy, extreme attention is required not to make a dissection and long-term dual antiplatelet treatment should be followed after stent implantation.
Angioplasty ; Brachytherapy ; Catheters ; Follow-Up Studies ; Humans ; Rhenium ; Seoul ; Stents* ; Thrombosis ; Ticlopidine

BACKGROUND AND OBJECTIVES: Intracoronary irradiation has emerged as a successful intervention for the treatment of restenosis. However, the radiation process is complex, difficult and hard to perform. On the contrary, intracoronary radiation therapy using a 188Re-DTPA-filled balloon system is simple and inexpensive. The short-term follow-up results of this system have been reported, but the long-term results remain to be elucidated. The object of this study is to evaluate the short and long-term follow-up results of intracoronary radiation using a 188ReDTPA-filled balloon system in restenotic lesions. SUBJECTS AND METHODS: Thirty-eight patients, with restenotic lesion after previous percutaneous coronary intervention, were selected from the SPARE trial (Seoul National University Post-Angioplasty RhEnium irradiation trial). There were 27 cases in the irradiation group, with 11 in the control group. Irradiation was performed in the restenotic lesions after successful interventions. The results of 6-month angiographic and 6-month and 3-year clinical follow-up data were compared between the two groups. RESULTS: A 6-month angiographic follow-up was performed in 33 patients (87%), 25 in the radiation group and 8 in control. Binary restenosis developed in 1 of 25 (4%) and 4 of 8 (50%) in the radiation and control groups, respectively (p=0.008). At the 6-month clinical follow-up, there were no significant differences in the event rates between the two groups. At the 3-year clinical follow-up, there was a significant difference in the target vessel revascularization: 2 of 27 (7.4%) and 5 of 11 (45.4%) in the radiation and control groups, respectively (p=0.017). There were no deaths or myocardial infarctions. CONCLUSION: Radiation therapy using a 188ReDTPA-filled balloon system is feasible, and may be effective in improving the long-term outcomes in restenotic lesions.
Angioplasty ; Follow-Up Studies* ; Humans ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Radiotherapy ; Rhenium

Angioplasty, Balloon, Coronary ; methods ; Coronary Restenosis ; prevention & control ; radiotherapy ; Drug-Eluting Stents ; adverse effects ; Humans ; Iridium ; Rhenium ; Xenon Isotopes

OBJECTIVETo investigate the inhibitory effects of (188)Re-labeled herceptin on the proliferation in vitro of breast carcinoma cell line (SKBR-3) overexpressing HER-2/neu proto-oncogene.

METHODSHerceptin was radiolabeled with (188)Re through a direct labeling method. SKBR-3 cells were cultured with (188)Re-Herceptin at different radioactivity doses (3.7x10(4), 18.5x10(4), 37x10(4), 55.5x10(4) and 74x10(4) Bq/ml) or with (188)Re-nmIgG and (188)ReO(4)(-) for comparison. The cell proliferation inhibition was determined with MTT colorimetric assay.

RESULTS(188)Re-Herceptin could markedly inhibit the growth of SKBR-3 cells in a radioactivity dose-dependent fashion, while the effect of (188)Re-nmIgG and (188)ReO(4)(-) showed rather poor inhibitory effect in vitro. The 50% inhibition doses (IC(50)) of (188)Re-Herceptin, (188)Re-nmIgG and (188)ReO(4)(-) were 76.1x10(4) Bq/L, 139.2x10(4) Bq/L and 175x10(4) Bq/L, respectively.

CONCLUSION(188)Re-Herceptin can effectively inhibit the growth of in vitro cultured breast cancer cells overexpressing HER-2/neu, and shows much potential for clinical use in beast cancer radioimmunotherapy.

Antibodies, Monoclonal ; chemistry ; pharmacology ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Immunotoxins ; pharmacology ; Radioisotopes ; chemistry ; pharmacology ; Receptor, ErbB-2 ; biosynthesis ; Rhenium ; chemistry ; pharmacology ; Trastuzumab

(188)Re(Rhenium) is easily obtained from an in-house (188)W/(188)Re generator that is similar to the current (99)Mo/(99m)Tc generator, making it very convenient for clinical use. This characteristic makes this radionuclide a promising candidate as a therapeutic agent. Polyethylenimine (PEI) is a cationic polymer and has been used as a gene delivery vector. Positively charged materials interact with cellular blood components, vascular endothelium, and plasma proteins. In this study, the authors investigated whether intratumoral injection of (188)Re labeled transferrin (Tf)-PEI conjugates exert the effect of radionuclide therapy against the tumor cells. When the diameters of the Ramos lymphoma (human Burkitt's lymphoma) xenografted tumors reached approximately 1 cm, 3 kinds of (188)Re bound compounds (HYNIC-PEI-Tf, HYNIC-PEI, (188)Re perrhenate) were injected directly into the tumors. There were increases in the retention of (188)Re inside the tumor when PEI was incorporated with (188)Re compared to the use of free 188Re. The (188)Re HYNIC-Tf-PEI showed the most retention inside the tumor (retention rate=approximately 97%). H&E stain of isolated tumor tissues showed that (188)Re labeled HYNIC-PEI-Tf caused extensive tumor necrosis. These results support (188)Re HYNIC-PEI-Tf as being a useful radiopharmaceutical agent to treat tumors when delievered by intratumoral injection.
Animals ; Burkitt Lymphoma/pathology/*radiotherapy ; Cations ; Female ; Injections, Intralesional ; Mice ; Mice, Inbred BALB C ; Pilot Projects ; Polyethyleneimine/chemistry/*pharmacology ; Radioisotopes/chemistry/*pharmacology ; Research Support, Non-U.S. Gov't ; Rhenium/chemistry/*pharmacology

Carcinoma, Hepatocellular ; diagnosis ; radiotherapy ; Follow-Up Studies ; Humans ; Iodized Oil ; administration & dosage ; Isotopes ; Liver Neoplasms ; diagnosis ; radiotherapy ; Palliative Care ; methods ; Radiopharmaceuticals ; administration & dosage ; Rhenium ; therapeutic use ; Terminally Ill ; Treatment Outcome

OBJECTIVETo study the effectiveness of radiation synovectomy with (188)Re-sulfide.

METHODSTwenty rabbit models of joint synovitis were injected intra-articularly with different doses of (188)Re-sulfide from 7.4 to 37.0 MBq. By pathological examination, the effects of (188)Re-sulfide on synovium and cartilage were evaluated. Clinically, 10 joints of 7 cases of hemophilic arthritis with (188)Re-sulfide radiation synovectomy were performed. MRI was taken before and after the synovectomy to evaluate the treatment effects.

RESULTSIn rabbit models, when (188)Re-sulfide dose larger than 14.8 MBq, the radiation effect on synovitis was remarkable, including thinning the thickened synovium and reducing the inflammatory cells. When radio-activity dose increased to 37.0 MBq, pathological damage was noted in cartilage. Clinical trial demonstrated that radiation synovectomy by (188)Re-sulfide could reduce the frequencies of intra-articular hemorrhage. MRI showed that edema and villi reduced.

CONCLUSIONSRadiation synovectomy using (188)Re-sulfide is effective on synovitis in hemophilic arthritis.

Animals ; Chlorides ; therapeutic use ; Disease Models, Animal ; Follow-Up Studies ; Hemophilia A ; complications ; Humans ; Injections, Intra-Articular ; Rabbits ; Rhenium ; therapeutic use ; Ruthenium Radioisotopes ; therapeutic use ; Sulfides ; Synovial Membrane ; radiation effects ; Synovitis ; etiology ; pathology ; radiotherapy

OBJECTIVETo evaluate the treatment results of stereotactic (186)Re intracavitary irradiation in the patients with craniopharyngioma.

METHODSNineteen patients were treated with stereotactic (186)Re intracavitary irradiation, including 12 males and 7 females (average age, 37.2 years). Among them 12 patients had a solitary cyst, whereas 7 patients with mixed structure (e.g., a large cyst with a small solid portion). The mean volume of the cystic portion of the tumor before irradiation was 8390 mm(3).

RESULTSThe patients were followed up for 6 months to 3 years. The retraction of the cyst was complete in 7 patients, cyst volume decreased more than 50% in 5 patients and less than 50% in 7 cases. Among the 8 patients with visual acuity deficit before irradiation, 5 were improved. No hypopituitarism occurred in patients with normal pituitary function before treatment. One of the 4 patients with hypopituitarism was improved, 3 of the 5 patients with diabetes insipidus was improved.

CONCLUSIONStereotactic (186)Re endocavitary irradiation for the treatment of cystic craniopharyngioma is a safe and effective procedure.

Adolescent ; Adult ; Brachytherapy ; methods ; Child ; Child, Preschool ; Craniopharyngioma ; radiotherapy ; Cysts ; radiotherapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pituitary Neoplasms ; radiotherapy ; Radioisotopes ; therapeutic use ; Rhenium ; therapeutic use ; Stereotaxic Techniques ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the effect of radioimmunotherapy with (188)Re-labeled herceptin in nude mice bearing nasopharyngeal carcinoma expressing HER2/neu proto-oncogene and explore the feasibility of (188)Re-herceptin for use as a chemical therapeutic and radioimmunotherapeutic agent.

METHODSA direct radiolabeling method was used to prepare (188)Re-Herceptin. Thirty-two nude mice bearing nasopharyngeal carcinoma were randomized into 4 groups (n=8) to receive single intravenous injection of (188)Re-Herceptin, intratumoral injection of (188)Re-Herceptin, (188)Re-nmIgG and (188)Re, respectively, all at the equivalent dose of 11.1 MBq (50 microl). Another 5 tumor-bearing mice received only intratumoral injection of 50 microl normal saline to serve as the control group. Two days after the injections, 3 mice were selected from each group (except for the control group) for biodistribution observation, and the rest mice were monitored for 4 consecutive weeks for tumor volume changes. Pathological examination of the tumor tissues was also performed.

RESULTSThe radioactivity uptake in the tumor was significantly greater whereas normal organ uptake significantly lower in the nude mice receiving intratumoral (188)Re-Herceptin injection than in those with intravenous (188)Re-Herceptin injection (11.53%ID/g vs 2.79%ID/g at 48 h). Intratumoral (188)Re-Herceptin injection caused greater inhibition of tumor growth at the 4th week as compared to the intravenous administration.

CONCLUSIONIntratumoral (188)Re-Herceptin administration can significantly inhibit the development of nasopharyngeal carcinoma in mice, and may potentially serve as a new clinical option of regional therapy for treating nasopharyngeal carcinoma overexpressing HER2/neu.

Animals ; Antibodies, Monoclonal ; administration & dosage ; Antibodies, Monoclonal, Humanized ; Injections, Intralesional ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; radiotherapy ; Neoplasm Transplantation ; Radioimmunotherapy ; methods ; Radioisotopes ; administration & dosage ; Random Allocation ; Receptor, ErbB-2 ; biosynthesis ; genetics ; Rhenium ; administration & dosage ; Trastuzumab

OBJECTIVETo analyze the biodistribution of (186)Re-lipiodol (RL) in patients with primary liver cancer (PLC) after hepatic arterial injection in attempt to assess the potential of RL as a radiopharmaceutical for the treatment of PLC.

METHODSRL was synthesized from (186)Rhenium and Lipiodol by a series of physical and chemical procedures. Doses of RL ranged from 1 110 MBq to 2 220 MBq per patient depending on the volume of tumor. Quantitative gamma camera imaging (ECT) and gamma counting of serum and urine were used to obtain data for dosimetry estimation. Serum tumor marker (AFP) level and shrinkage of tumor were used to evaluate the therapeutic efficacy of RL.

RESULTSIn the hepatic tumor, RL was selectively retained and radioactivity was very high throughout this study. The ratio of tumor concentration to the normal liver tissue concentration (T/NT ratio) was 10 - 14 at 48 hours after injection of RL. The main side effects of this therapy were transient fever and anorexia. No unacceptable toxicity was observed. In 100% of the patients, the therapy resulted in a significant decrease of AFP level and reduction of tumor volume.

CONCLUSIONThe biodistribution and imaging results demonstrated RL localized selectively in tumor, and that RL may be a potential internal radiopharmaceutical agent for the treatment of primary liver cancer.

Adult ; Aged ; Carcinoma, Hepatocellular ; drug therapy ; metabolism ; Drug Carriers ; Humans ; Infusions, Intra-Arterial ; Iodized Oil ; administration & dosage ; Liver Neoplasms ; drug therapy ; metabolism ; Male ; Middle Aged ; Radiopharmaceuticals ; adverse effects ; pharmacokinetics ; therapeutic use ; Radiotherapy Dosage ; Rhenium ; adverse effects ; pharmacokinetics ; therapeutic use ; Treatment Outcome