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• W2097524894 abstract "Objective: The aim of the present study was to develop a 177Lu-labeled porphyrin derivative having favorable characteristics for use in targeted radiotherapy of cancer and to evaluate its biological behavior in mouse tumor models with respect to its effectiveness in tumor regression. Owing to the inherent affinity of porphyrins to accumulate in the tumors, suitably modified porphyrin derivative was chosen as the vehicle for the targeted delivery of the radionuclide. 177Lu was preferred as the radionuclide of choice due to its suitable nuclear decay characteristics [Eβ(max) = 497 keV, Eγ = 208 keV (11%), 113 keV (6.4%)], comparatively longer half-life (6.73 d) and ease of production in adequate quantity and sufficiently high specific activity using medium flux research reactors. Methods: A novel porphyrin analogue, 5,10,15,20-tetrakis[4-carboxymethyleneoxyphenyl]porphyrin was synthesized inhouse and coupled with a macrocyclic bi-functional chelating agent, namely p-amino-benzyl-1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraacetic acid. The porphyrin-BFCA conjugate was labeled with 177Lu and the biological behavior of the radiolabeled conjugate was studied by biodistribution and imaging in Swiss mice bearing either fibrosarcoma or thymic lymphoma tumors. Effectiveness of the agent in controlling the growth of tumor volumes was also studied by administering various doses of the radiolabeled preparation in the mouse tumor models. Results: 177Lu-labeled porphyrin-BFCA conjugate was prepared with high radiochemical purity ( > 99%) and adequate invitro stability. Biodistribution and imaging studies revealed good uptake and retention of the agent in the tumors with encouraging tumor to blood and tumor to muscle ratios at various post-administration time points. Tumor regression studies showed that the administration of the agent increased the average tumor doubling time and decreased the average specific growth rate substantially in both the types of tumors. However, thymic lymphoma was found to be more sensitive to the radiolabeled conjugate compared to fibrosarcoma. Conclusion: Preliminary biological evaluation and tumor regression studies carried out in two different tumor models in Swiss mice exhibited the promising nature of 177Lu-labeled porphyrin-BFCA conjugate as an agent for targeted tumor therapy. However, further detailed investigations are warranted to evaluate the true potential of the developed agent. Keywords: Fibrosarcoma, 177Lu, porphyrin, targeted radiotherapy, thymic lymphoma, tumor regression, Transplantation, Thymic Lymphoma Tumor, Radiochemical Processing, Scintiimaging Studies" @default.
• W2097524894 created "2016-06-24" @default.
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• W2097524894 date "2011-04-01" @default.
• W2097524894 modified "2023-10-18" @default.
• W2097524894 title "Studies on Efficacy of a Novel 177Lu-Labeled Porphyrin Derivative in Regression of Tumors in Mouse Model" @default.
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• W2097524894 doi "https://doi.org/10.2174/1874471011104020150" @default.
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