Impact of PKM Linkers on Biodistribution Characteristics of the 99mTc-Labeled Cyclic RGDfK Dimer

Abstract

This report describes synthesis of three new cyclic RGDfK peptide conjugates, HYNIC−PKM−SU016 (PKM = E, K and PEG4) and in vivo evaluation of the impact of PKM linkers on biodistribution characteristics of their ternary ligand complexes [^99mTc(HYNIC−PKM−SU016)¹(tricine)(TPPTS)] in athymic nude mice bearing the MDA-MB-435 human breast cancer xenografts. Results from biodistribution studies show that PKM linkers have minimal impact on the integrin α_vβ₃ binding capability of radiotracers. Even though they have different charges under physiological conditions, all three linkers (E, K, and PEG4) are able to reduce the uptake of ^99mTc-labeled E[c(RGDfK)]₂ in blood, kidneys, liver, and lungs, and increase target-to-background (T/B) ratios at >30 min postinjection. E and K may have advantages over PEG4 due to a combination of relatively low liver uptake and high tumor/liver and tumor/lung ratios of ternary ligand complexes [^99mTc(HYNIC−PKM−SU016)(tricine)(TPPTS)] (PKM = E and K).