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Assessment of 177Lu-labeled carboxyl-terminated polyamidoamine (PAMAM) dendrimer-RGD peptide conjugate
Journal of Peptide Science  (IF1.905),  Pub Date : 2021-08-30, DOI: 10.1002/psc.3366
Kusum Vats, Rohit Sharma, Amit Kumar Sharma, Haladhar D. Sarma, Drishty Satpati

Structurally unique polyamidoamine (PAMAM) dendrimers implanted with targeting biological moiety along with complexed radiometal constitute a favorable nano-system for diagnosis and therapy of targeted tumor sites. In the present study, carboxyl functionalities of PAMAM- generation 4 dendrimer (PAMAM-G4-COOH) were conjugated with ε-amino group of lysine of cRGDfK peptide to impart integrin αvβ3 targeting capability. Reaction of p-NH2-Bn-DOTA with PAMAM was accomplished via acid-amine coupling using EDC/NHS for 177Lu-complexation. 177Lu-labeled nano-system, 177Lu-PAMAM-DOTA-cRGDfK demonstrated receptor-mediated uptake in murine melanoma B16F10 cells during in vitro cell uptake studies. In vivo biodistribution studies demonstrated low tumor uptake and retention of 177Lu-PAMAM-DOTA-cRGDfK which may be attributed to rapid blood clearance. However, fast clearance from non-target organs resulted in higher target to background ratio. Tumor uptake of targeted nano-system, 177Lu-PAMAM-DOTA-cRGDfK was observed to be significantly (p < 0.05) higher in comparison to 177Lu-PAMAM-DOTA without the targeting peptide. Inhibition studies with unlabeled cRGDfK resulted in 60% reduction in tumor uptake of 177Lu-PAMAM-DOTA-cRGDfK, indicating specificity of the developed nano-system towards integrin αvβ3 receptors.