Affiliation:
1. Department of Radiology, University of Colorado Denver, Aurora, CO 80045, USA
2. Versant Medical Physics and Radiation Safety, Richland, WA 99354, USA
3. Department of Medical Oncology, University of Colorado Denver, Aurora, CO 80045, USA
Abstract
The aim of this study was to evaluate the effect of linker on tumor targeting and biodistribution of 67Cu-NOTA-PEG2Nle-CycMSHhex {67Cu-1,4,7-triazacyclononane-1,4,7-triyl-triacetic acid-polyethylene glycol-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2} and 67Cu-NOTA-GGNle-CycMSHhex {67Cu-NOTA-GlyGlyNle-CycMSHhex} on melanoma-bearing mice. NOTA-PEG2Nle-CycMSHhex and NOTA-GGNle-CycMSHhex were synthesized and purified by HPLC. The biodistribution of 67Cu-NOTA-PEG2Nle-CycMSHhex and 67Cu-NOTA-GGNle-CycMSHhex was determined in B16/F10 melanoma-bearing C57 mice. The melanoma imaging property of 67Cu-NOTA-PEG2Nle-CycMSHhex was further examined in B16/F10 melanoma-bearing C57 mice. 67Cu-NOTA-PEG2Nle-CycMSHhex exhibited higher tumor uptake than 67Cu-NOTA-GGNle-CycMSHhex at 2, 4, and 24 h post-injection. The tumor uptake of 67Cu-NOTA-PEG2Nle-CycMSHhex was 27.97 ± 1.98, 24.10 ± 1.83, and 9.13 ± 1.66% ID/g at 2, 4, and 24 h post-injection, respectively. Normal organ uptake of 67Cu-NOTA-PEG2Nle-CycMSHhex was lower than 2.6% ID/g at 4 h post-injection, except for kidney uptake. The renal uptake of 67Cu-NOTA-PEG2Nle-CycMSHhex was 6.43 ± 1.31, 2.60 ± 0.79, and 0.90 ± 0.18% ID/g at 2, 4, and 24 h post-injection, respectively. 67Cu-NOTA-PEG2Nle-CycMSHhex showed high tumor to normal organ uptake ratios after 2 h post-injection. The B16/F10 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT) using 67Cu-NOTA-PEG2Nle-CycMSHhex as an imaging probe at 4 h post-injection. The favorable tumor targeting and biodistribution properties of 67Cu-NOTA-PEG2Nle-CycMSHhex underscored its potential as an MC1R-targeted therapeutic peptide for melanoma treatment.