Abstract
Malignant melanoma is an aggressive cancer with poor prognosis. Very late antigen-4 (VLA-4) is overexpressed in melanoma and many other tumors, making it an attractive target for developing molecular diagnostic and therapeutic agents. We compared Al18F- and 68Ga-labeled LLP2A peptides for PET imaging of VLA-4 expression in melanoma. The peptidomimetic ligand LLP2A was modified with chelator 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA), and the resulting NOTA-PEG4-LLP2A peptide was then radiolabeled with Al18F or 68Ga. The two labeled peptides were assayed for in vitro and in vivo VLA-4 targeting efficiency. Good Al18F and 68Ga radiolabeling yields were achieved, and the resulting PET tracers showed good serum stability. In the in vivo evaluation of the B16F10 xenograft mouse model, both tracers exhibited high accumulation with good contrast in static PET images. Compared with 68Ga-NOTA-PEG4-LLP2A, Al18F-NOTA-PEG4-LLP2A resulted in relatively higher background, including higher liver uptake (1 h: 20.1 ± 2.6 vs. 15.3 ± 1.7%ID/g, P < 0.05; 2 h: 11.0 ± 1.2 vs. 8.0 ± 0.8%ID/g, P < 0.05) and lower tumor-to-blood ratios (2.5 ± 0.4 vs. 3.3 ± 0.5 at 1 h, P < 0.05; 5.1 ± 0.9 vs. 7.3 ± 0.6 at 2 h, P < 0.01) at some time points. The results obtained from the mice blocked with unlabeled peptides and VLA-4-negative A375 xenografts groups confirmed the high specificity of the developed tracers. Despite the relatively high liver uptake, both Al18F-NOTA-PEG4-LLP2A and 68Ga-NOTA-PEG4-LLP2A exhibited high VLA-4 targeting efficacy with comparable in vivo performance, rendering them promising candidates for imaging tumors that overexpress VLA-4.