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Purpose <p>Melanoma is a highly aggressive skin cancer with poor prognosis, highlighting the need for early detection. This study aims to develop a <sup>99m</sup>Tc-labeled single photon emission computed tomography (SPECT) probe targeting melanin to improve melanoma detection with enhanced specificity and cost-effectiveness.</p> Methods <p>Six potential <sup>99m</sup>Tc-labeled probes were synthesized by conjugating small molecules with nitrogen-rich fatty chains or cyclic structures to <sup>99m</sup>Tc. These <sup>99m</sup>Tc-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.</p> Results <p>These six probes exhibited high radiolabeling yields (&gt; 95%) and radiochemical purities (&gt; 95%). In vitro cell uptake and blocking experiments demonstrated their binding capability and specificity for melanin. Among these probes, <sup>99m</sup>Tc-SMIC-4006 displayed the highest tumor uptake (5.18 ± 1.55%ID/g at 1&#xa0;h) and significantly higher uptake in B16F10 xenografts compared to non-melanotic A375 xenografts (<i>p</i> &lt; 0.01). The initial tumor-to-blood ratio for <sup>99m</sup>Tc-SMIC-4006 was 4.30 ± 0.63 at 1&#xa0;h, increasing to 10.27 ± 5.13 at 6&#xa0;h. Importantly, SPECT/CT imaging of <sup>99m</sup>Tc-SMIC-4006 clearly delineated B16F10 tumor regions with high contrast, while A375 xenografts showed minimal uptake.</p> Conclusion <p><sup>99m</sup>Tc-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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年4月21日

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  • Ji Tao,
  • Rui Cao,
  • Zhe Lei,
  • Xiao Wang,
  • Renli Luo,
  • Yuanyuan Zhou,
  • Yanlin Li,
  • Xiaoping Xu,
  • Xiaosheng Liu,
  • Chunrong Qu,
  • Shaoli Song,
  • Mei Tian,
  • Zhen Cheng

摘要

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.