ABSTRACT
Background & objectives: Yttrium-90 (90Y)-based radioembolization has been employed to treat hepatocellular carcinoma (HCC) as commercial radioactive glass and polymeric resin microspheres. However, in India and other Asian countries, these preparations must be imported and are expensive, validating the need for development of indigenous alternatives. This work was aimed to develop an economically and logistically favourable indigenous alternative to imported radioembolizing agents for HCC therapy. Methods: The preparation of 90Y-labelled Biorex 70 microspheres was optimized and in vitro stability was assessed. Hepatic tumour model was generated in Sprague-Dawley rats by orthotopic implantation of N1S1 rat HCC cell line. In vivo localization and retention of the 90Y-labelled Biorex 70 microspheres was assessed for seven days, and impact on N1S1 tumour growth was studied by histological examination and biochemical assays. Results: Under optimal conditions, >95% 90Y-labelling yield of Biorex70 resin microspheres was obtained, and these showed excellent in vitro stability of labelling (>95%) at seven days. In animal studies, 90Y-labelled Biorex 70 microspheres were retained (87.72±1.56% retained in liver at 7 days). Rats administered with 90Y-labelled Biorex 70 microspheres exhibited lower tumour to liver weight ratio, reduced serum alpha-foetoprotein level and greater damage to tumour tissue as compared to controls. Interpretation & conclusions: 90Y-labelled Biorex 70 microspheres showed stable retention in the liver and therapeutic effect on tumour tissue, indicating the potential for further study towards clinical use.
ABSTRACT
Background & objectives: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin’s lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with 90Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. Methods: Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. Results: Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with 90Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with 90Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant Kd for 90Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of 90Y-DOTA-rituximab. Interpretation & conclusions: p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90Y was carried out. In vitro studies carried out in Raji cells showed the specificity of the radiolabelled conjugate suggesting the potential uitability of the formulation as a radiopharmaceutical for therapy of NHL.
ABSTRACT
Background & objectives: In recent years, brachytherapy involving permanent radioactive seed implantation has emerged as an effective modality for the management of cancer of prostate. 125I-Ocu-Prosta seeds were indigenously developed and studies were carried out to assess the safety of the indigenously developed 125I-Ocu-Prosta seeds for treatment of prostate cancer. Methods: Animal experiments were performed to assess the likelihood of in vivo release of 125I from radioactive seeds and migration of seeds implanted in the prostate gland of the rabbit. In vivo release of 125I activity was monitored by serial blood sampling from the auricular vein and subsequent measurement of 125I activity. Serial computed tomography (CT) scans were done at regular intervals till 6 months post implant to assess the physical migration of the seeds. Results: The laser welded seeds maintained their hermeticity and prevented the in vivo release of 125I activity into the blood as no radioactivity was detected during follow up blood measurements. Our study showed that the miniature 125I seeds were clearly resolved in CT images. Seeds remained within the prostate gland during the entire study period. Moreover, the seed displacement was minimal even within the prostate gland. Interpretation & conclusions: Our findings have demonstrated that indigenously developed 125I-Ocu-Prosta seeds may be suitable for application in treatment of prostate cancer.
ABSTRACT
Aim: To report our experience of brachytherapy using ‘BARC I‑125 Ocu‑Prosta seeds’ for the management of intraocular tumors with regard to tumor control, globe preservation visual outcome, and patient survival at Sankara Nethralaya, Chennai, India between September 2003 and May 2011. Materials and Methods: We reviewed records of 35 eyes of 35 patients who underwent ophthalmic brachytherapy between September 2003 and May 2011. Twenty‑one cases had choroidal melanoma, nine had childhood retinoblastoma, two had adult‑onset retinoblastoma, and there were one case each of vasoproliferative tumor, retinal angioma, and ciliary body melanoma. Brachytherapy was administered using a 15‑ or 20‑mm gold plaque with or without a notch. Brachytherapy was the primary treatment modality in all tumors other than retinoblastoma, wherein brachytherapy was done post chemoreduction for residual tumor. Results: For choroidal melanomas, the mean radiation dose was 68.69 ± 15.07 (range, 47.72-94.2) Gy. The eye salvage rate was 13/20 (65%) and tumor control rate was 16/20 (80%) at an average follow‑up of 24.43 ± 24.75 (range, 1.5-87.98) months. For retinoblastoma, the mean dose was 45.85 ± 3.90 (range, 39.51-50.92) Gy. The eye salvage rate and tumor control rate was 5/6 (83.3%) at an average follow‑up of 38.36 ± 31.33 (range, 4.14-97.78) months. All eyes with retinoblastoma needed additional focal therapy for tumor control and eye salvage. Conclusion: The results of this retrospective study confirms that the use of ‘BARC I‑125 Ocu‑Prosta seeds’ in episcleral plaques to treat intraocular tumors offers a viable option for the management of intraocular cancers.
ABSTRACT
Context: To analyze the results of episcleral plaque brachytherapy using indigenous Bhabha Atomic Research Centre (BARC) Iodine-125 Ocu-Prosta seeds for the management of intraocular tumors from a single institute. AIM: To report our initial experience and learning curve on the use of ‘BARC I-125 Ocu-Prosta seeds’ for the management of intraocular tumors such as choroidal melanomas, retinoblastomas and vasoproliferative tumors (VPT). Materials and Methods: We retrospectively reviewed 13 eyes of 13 patients who underwent ophthalmic brachytherapy between May 2008 to March 2012. Nine cases had choroidal melanomas; three had retinoblastomas while one case had VPT. Results: For choroidal melanomas the average apical diameter before brachytherapy was 7.6 mm and average largest basal diameter was 12.1 mm, respectively, which reduced to 4.2 mm and 7.7 mm after the procedure at an average follow-up of 24 months (range 10-43 months). Retinoblastoma and VPT also showed good regression after brachytherapy. Conclusion: Plaque radiotherapy using 125I seeds can be performed under peribulbar anesthesia and provides a viable option for the management of intraocular cancer with minimal invasiveness and surgical complications. Patients in our studies experienced excellent local tumor control. With the availability of indigenous ‘BARC I-125 Ocu-Prosta seeds’ locally, cost effective ophthalmic brachytherapy can be performed in India.