RESUMO
The effectiveness of 166Ho-chitosan complex as a radiopharmaceutical for trans-arterial radiation therapy of liver cancer has been established in clinical trials. We have developed a simple kit-bade strategy for convenient formulation of therapeutically relevant doses of 166Ho-chitosan complex in a hospital radiopharmacy in order to facilitate its widespread utilization. Quality control studies established the suitability of the radiopharmaceutical formulated using the developed strategy for in vivo administration. Biodistribution studies in normal Wistar rats showed excellent retention of the radiopharmaceutical in the liver, thus, paving the way towards utility of this approach in clinical context.
Assuntos
Quitosana/química , Hólmio/química , Neoplasias Hepáticas/radioterapia , Radioisótopos/química , Compostos Radiofarmacêuticos/uso terapêutico , Animais , Relação Dose-Resposta a Droga , Feminino , Humanos , Fígado/metabolismo , Neoplasias Hepáticas/metabolismo , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética , Ratos Wistar , Distribuição TecidualRESUMO
This paper describes the evaluation of [(R)-2-Amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-pentaacetic acid (CHX-A''-DTPA-NCS) and 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-NCS) as bifunctional chelators for 177Lu. While 177Lu-CHX-A''-DTPA-NCS could be obtained in high yields at equimolar ratios of lutetium to CHX-A''-DTPA-NCS, >95% yield of 177Lu-NOTA-NCS could be achieved at 1:2M ratio of lutetium to NOTA-NCS. Trace metals reduced the yields of 177Lu-NOTA-NCS significantly as compared to 177Lu-CHX-A''-DTPA-NCS. In vitro stability of 177Lu-CHX-A''-DTPA-NCS was also superior to 177Lu-NOTA-NCS. It could be concluded from this study that among the two chelators evaluated, CHX-A''-DTPA-NCS is more appropriate for preparation of 177Lu radiopharmaceuticals.
Assuntos
Quelantes/química , Lutécio/química , Radioisótopos/química , Compostos Radiofarmacêuticos/química , Estabilidade de Medicamentos , Durapatita/química , Compostos Heterocíclicos/sangue , Compostos Heterocíclicos/química , Compostos Heterocíclicos com 1 Anel , Humanos , Técnicas In Vitro , Lutécio/sangue , Ácido Pentético/análogos & derivados , Ácido Pentético/sangue , Ácido Pentético/química , Radioisótopos/sangue , Compostos Radiofarmacêuticos/sangue , Oligoelementos/químicaRESUMO
The clinical applications of radiolabeled somatostatin analogue (177) Lu-DOTA-Tyr(3) -Thr(8) -Octreotide ((177) Lu-DOTATATE) constitute a promising treatment option for patients with disseminated and inoperable neuroendocrine (NET) tumors. Formulation of (177) Lu-DOTATATE in hospital radiopharmacy under aseptic conditions in a safe and reliable manner is a major constraint for its extensive use. The present work was intended to develop a kit for the safe preparation of the therapeutic radiopharmaceutical, viz. (177) Lu-DOTATATE of high quality that can be easily adapted at conventional hospital radiopharmacies. Single vial kits of DOTATATE were formulated and evaluated for suitability for radiolabeling as well as stability on its storage. Patient dose of (177) Lu-DOTATATE (7.4 GBq) could be successfully prepared using semi-automated in-house setup that assures safe handling and high yields of product of pharmaceutical purity suitable for clinical use. Fast clearance of activity via renal route was observed in preclinical biodistribution studies of (177) Lu-DOTATATE carried out in normal Swiss mice. Deployment of in-house produced (177) LuCl3 , cold kits and easy adaptability of synthesis setup at hospital radiopharmacy for preparation is likely to expand applications of peptide receptor radionuclide therapy.
Assuntos
Meios de Contraste/síntese química , Marcação por Isótopo/métodos , Lutécio/química , Octreotida/análogos & derivados , Compostos Organometálicos/síntese química , Compostos Radiofarmacêuticos/síntese química , Kit de Reagentes para Diagnóstico , Marcação por Isótopo/instrumentação , Teste de Materiais , Octreotida/síntese química , Radioisótopos/químicaRESUMO
Lutetium-177 is an assured therapeutic radionuclide with favorable half-life and suitable ß(-) energy. Radiolabeled (177)Lu-EDTMP (Ethylenediamine tetramethylene phosphonic acid) is by and large used for bone pain palliation in cancer patients. In vitro cell studies are carried out in osteosarcoma cells MG-63 to evaluate the combined effect of anticancer drug camptothecin (CPT) and (177)Lu-EDTMP. Two concentrations of (177)Lu-EDTMP (3.7 and 37 MBq) were incubated with MG63 cell line for 48 hours with and without pretreatment of CPT (10 nM) for 1 hour. After completion of incubation, the cells were harvested and cellular toxicity was estimated by LDH, MTT, and trypan blue dye. Apoptotic DNA fragmentation was estimated by ELISA kit. The expression of proteins such as bcl2, PARP, and MAPK (mitogen-activated protein kinase) that were related to apoptotic signaling pathways was assessed by western blotting. The results indicated that cellular toxicity and apoptosis were relatively higher in MG63 cells that were treated with CPT prior to treating with (177)Lu-EDTMP in comparison with the corresponding individual controls.
