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 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. Two radiopeptides could clearly visualize xenografts in SPECT images at 3, 24 and 48 h p.i. indicating their potential for further exploration as HER2-targeting probes. The encouraging in vivo profile of PEG construct, 177 Lu-DOTA-PEG 4 -A9 incentivizes future studies for clinical applications.