177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) alone has lesser potential in the clinical setting of neuroendocrine tumor (NET) with large bulky disease and nonhomogeneous somatostatin receptors (SSTR) distribution, owing to lower energy (Eβmax 0.497 MeV) and a shorter particle penetration range (maximum 2–4 mm) of 177 Lu. In large bulky NETs, 90 Yttrium ( 90 Y) has the theoretical advantages because of a longer beta particle penetration range (a maximum soft tissue penetration of 11 mm). Therefore, a combination of 177 Lu and 90 Y is a theoretically sound concept that can result in better response in metastatic NET with large-bulky lesion and non-homogeneous SSTR distribution. The aim of the study was to determine the feasibility of combining 90 Y-DOTATATE with 177 Lu-DOTATATE PRRT as sequential duo-PRRT in metastatic NET with (≥5 cm) including the post 90 Y-DOTATATE-PRRT imaging and also to determine early toxicity of the duo-PRRT approach. A total of 9 patients received combination of 177 Lu-DOTATATE with 90 Y-DOTATATE (indigenously prepared and approved) through sequential duo-PRRT approach. These 9 NET patients were included and analyzed in this study. All 9 patients had undergone post-PRRT 90 Y-DOTATATE imaging, including a whole-body planar bremsstrahlung imaging followed by regional single-photon emission computed tomography (SPECT)-computed tomography (CT) imaging and also a regional positron emission tomography–computed tomography imaging. Grading of 90 Y-DOTATATE and 177 Lu-DOTATATE uptake was done on post-PRRT imaging by both modalities. The size of the lesions ranged from 5.5 cm to 16 cm with average size of 10 cm before sequential duo-PRRT was decided. Sequential duo-PRRT was administered because of stable, unresponsive disease following 177 Lu-DOTATATE in 5 patients (55.6%), progressive disease after 177 Lu-DOTATATE in 2 patients (22.2%), and with neoadjuvant intent in 2 patients (22.2%). The total cumulative dose of 177 Lu-DOTATATE before duo-pRRT ranged from 11.84 GBq to 37 GBq per patient and average administered dose of 27.21 GBq per patient in this study. Out of 9 patients, 8 patients received single cycle of 90 Y-DOTATATE (ranging from 2.66 GBq to 3.4 GBq per patient with average administered dose of 3.12 GBq per patient). One patient received two cycles of 90 Y-DOTATATE (total dose of 6.2 GBq). Out of 9 patients, 8 patients showed excellent tracer concentration in lesions on post-PRRT 90 Y-DOTATATE imaging and the remaining 1 patient showed fairly adequate 90 Y-DOTATATE tracer uptake in lesion on visual anal...
The objective of the present work is to evaluate the ability of the radiolabeled PAMAM dendrimers (polyamidoamine) towards facilitating the delivery of an in‐house synthesized porphyrin derivative in the tumorous lesions to evaluate their candidature for possible application in endo‐radionuclide therapy. For this, PAMAM particles were conjugated with a porphyrin derivative namely, 5,10,15,20‐tetrakis‐(4‐carboxymethyleneoxyphenyl)porphyrin (STAP), synthesized in‐house following a two‐step reaction. The average number of porphyrin molecules loaded per PAMAM particle was evaluated using ultraviolet‐visible spectrophotometry and was found to be approximately 2. STAP conjugated PAMAM particles were further conjugated with p‐NCS‐benzyl‐DOTA (subsequently referred as DOTA) to facilitate radiolabeling with 177Lu. On an average, two p‐NCS‐benzyl‐DOTA molecules were observed to be attached per PAMAM‐STAP particle. DOTA‐PAMAM‐STAP conjugate was radiolabeled with 177Lu with a final radiochemical purity of >95%, which was determined by paper chromatography using two different mobile phases viz. 0.1 M sodium citrate buffer (pH 5.0) and 10 mM DTPA. Biological behavior of [177Lu]Lu‐DOTA‐PAMAM‐STAP conjugate was investigated in fibrosarcoma bearing Swiss mice model wherein accumulation of radiolabeled particles was observed in liver, GIT, spleen, and kidneys at 3 h post‐administration. However, accumulated activity exhibited rapid clearance from majority of the organs at 24 h post‐administration. [177Lu]Lu‐DOTA‐PAMAM‐STAP conjugate exhibited an appreciable uptake in tumor mass [6.09 ± 1.22 percentage injected activity/organ (% IA/organ)] at 3 h post‐administration (p.i.) which was found to reduce to 1.05 ± 0.13 % IA/organ at 24 h post‐administration. The results obtained in biodistribution studies were further corroborated through scintigraphic imaging performed in the same animal model. Despite of an appreciable accumulation in tumor mass, the lower retention of the [177Lu]Lu‐DOTA‐PAMAM‐STAP conjugate therein, at longer time point (24 h p.i.) may limit its possible potential as a radio‐therapeutic agent and indicates towards need for further structural manoeuvring to attain favorable in vivo performance.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.