Development of ^99mTc-labeled melanin-targeted probes for SPECT imaging of melanoma.

Abstract

Melanoma is a highly aggressive skin cancer with poor prognosis, highlighting the need for early detection. This study aims to develop a ^99mTc-labeled single photon emission computed tomography (SPECT) probe targeting melanin to improve melanoma detection with enhanced specificity and cost-effectiveness. Six potential ^99mTc-labeled probes were synthesized by conjugating small molecules with nitrogen-rich fatty chains or cyclic structures to ^99mTc. These ^99mTc-complexes were then assessed in vitro for their lipid-water partition coefficient, radiochemical stability, and cellular uptake. In vivo studies included biodistribution, SPECT/CT imaging, pharmacokinetics, stability and biocompatibility studies were conducted in various mouse models. These six probes exhibited high radiolabeling yields (> 95%) and radiochemical purities (> 95%). In vitro cell uptake and blocking experiments demonstrated their binding capability and specificity for melanin. Among these probes, ^99mTc-SMIC-4006 displayed the highest tumor uptake (5.18 ± 1.55%ID/g at 1 h) and significantly higher uptake in B16F10 xenografts compared to non-melanotic A375 xenografts (p < 0.01). The initial tumor-to-blood ratio for ^99mTc-SMIC-4006 was 4.30 ± 0.63 at 1 h, increasing to 10.27 ± 5.13 at 6 h. Importantly, SPECT/CT imaging of ^99mTc-SMIC-4006 clearly delineated B16F10 tumor regions with high contrast, while A375 xenografts showed minimal uptake. ^99mTc-SMIC-4006 is a promising SPECT probe for melanoma imaging, offering high tumor specificity, excellent uptake, and ideal tumor-to-background contrast, with strong potential for clinical application.