Synthesis and comparative evaluation of (177)Lu-labeled PEG and non-PEG variant peptides as HER2-targeting probes

Highest global cancer incidence of female breast cancer is a matter of great concern. HER2-positive breast cancers have high mortality rate hence detection at an early stage is vital for successful treatment, improved cancer care and survival rate. Radiolabeled peptides have emerged as new alternatives to radiolabeled antibodies to overcome the limitations of slow clearance and uptake in non-target tissues. Herein, DOTA-A9 peptide and its pegylated variant were constructed on solid phase and radiolabeled with [(177)Lu]LuCl(3). [(177)Lu]DOTA-A9 and [(177)Lu]DOTA-PEG(4)-A9 displayed high binding affinity (K(d) = 48.4 ± 1.4 and 55.7 ± 12.3 nM respectively) in human breast carcinoma SKBR3 cells. Two radiopeptides exhibited renal excretion and rapid clearance from normal organs. Uptake in SKBR3 tumor and tumor-to-background ratios were significantly higher (p < 0.05) for [(177)Lu]DOTA-PEG(4)-A9 at the three time points investigated. Xenografts could be clearly visualized by [(177)Lu]DOTA-PEG(4)-A9 in SPECT images at 3, 24 and 48 h p.i. indicating the potential for further exploration as HER2-targeting probe. The encouraging in vivo profile of PEG construct, [(177)Lu]DOTA-PEG(4)-A9 incentivizes future studies for clinical applications.