Development of a Novel HER2-Targeted Peptide Probe for Dual-Modal Imaging of Tumors

Human
epidermal growth factor receptor 2 (HER2) may serve
as a
valid target for diagnosis of cancer. The probes with capability for
near-infrared window one region II (NIR-II) and positron emission
tomography (PET) dual-modal imaging are highly desired for HER2-positive
tumor detection. Herein, three HER2-targeted peptides were designed
and further modified with indocyanine green (ICG) and 2,2′,2″,2″-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic
acid (DOTA), which were used for NIR-II imaging and complexation with 68Ga for PET. Among the resulted probes (DOTA-ZC01-ICG, DOTA-KSP-ICG,
and DOTA-ZC02-ICG), NIR-II imaging revealed that DOTA-ZC02-ICG had
the best tumor imaging performance in SKOV3 tumor-bearing mice. The
highest T/N ratio (5.4) was achieved at 4 h post-injection. Furthermore,
DOTA-ZC02-ICG was radiolabeled with 68Ga to generate [68Ga]-DOTA-ZC02-ICG for PET, and it clearly delineated at 0.5,
1, and 2 h post-injection. The tumor uptake reached 1.9 %ID/g at 0.5
h, and the tumor uptakes were significantly inhibited in the blocking
study (p < 0.05). Overall, it provides a promising
technique for tumor dual-modal imaging and a new molecular scaffold
for developing HER2-targeted theranostic agents.