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Background <p>The tumor sink effect refers to the sequestration of a radiopharmaceutical compound by tumors, leading to a reduced bioavailability in non-target organs and potential alterations in radiopharmaceuticals distribution. This phenomenon has been widely studied in neuroendocrine, thyroid, and prostate cancers but remains unexplored for melanin-targeting radiopharmaceuticals in metastatic melanoma. [<sup>131</sup>I]ICF01012, an arylcarboxamide-derived radiopharmaceutical developed by our team, binds specifically to intra- and extracellular melanin. Given its high ocular uptake, we investigated whether tumor burden influences its biodistribution, particularly in organs at risk such as eyes.</p> Results <p>We conducted an ex vivo biodistribution study using syngeneic murine melanoma models (B16-F10, B16-OVA, B16BL6) and correlated tumor volume with radiopharmaceutical uptake. In models, γ-counting revealed significant tumor uptake (18.8 ± 4.5 IA%/g at 24&#xa0;h after injection of [<sup>131</sup>I]ICF01012), which was inversely correlated with ocular uptake (r = -0.7485, p &lt; 0.0001). A significant reduction in ocular uptake was observed in mice with large tumor burdens (-41.8% at 24&#xa0;h, -47.4% at 72&#xa0;h, p = 0.022).</p> Conclusion <p>These findings suggest that tumor burden impacts [<sup>131</sup>I]ICF01012 distribution in non-target organs, with potential clinical implications for dosimetry and toxicity mitigation in radiopharmaceutical therapy for metastatic melanoma. Further studies are needed to refine dosimetric models and assess the translational relevance of this effect in human subjects.</p> Graphical abstract <p></p>

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Tumor sink effect on melanin-ligand [131I]ICF01012 in melanoma and its implications for targeted radionuclide therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月26日

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  • Elodie Jouberton,
  • Sophie Besse,
  • Tommy Billoux,
  • Philippe Auzeloux,
  • Sébastien Schmitt,
  • Jean-Michel Chezal,
  • Nicolas Sas,
  • Laurine Noirault,
  • Manon Auriol,
  • Sophie Levesque,
  • Marine Delmas,
  • Benjamin Chaussin,
  • Emmanuel Chautard,
  • Elisabeth Miot-Noirault,
  • Jacques Rouanet,
  • Florent Cachin

摘要

Background

The tumor sink effect refers to the sequestration of a radiopharmaceutical compound by tumors, leading to a reduced bioavailability in non-target organs and potential alterations in radiopharmaceuticals distribution. This phenomenon has been widely studied in neuroendocrine, thyroid, and prostate cancers but remains unexplored for melanin-targeting radiopharmaceuticals in metastatic melanoma. [131I]ICF01012, an arylcarboxamide-derived radiopharmaceutical developed by our team, binds specifically to intra- and extracellular melanin. Given its high ocular uptake, we investigated whether tumor burden influences its biodistribution, particularly in organs at risk such as eyes.

Results

We conducted an ex vivo biodistribution study using syngeneic murine melanoma models (B16-F10, B16-OVA, B16BL6) and correlated tumor volume with radiopharmaceutical uptake. In models, γ-counting revealed significant tumor uptake (18.8 ± 4.5 IA%/g at 24 h after injection of [131I]ICF01012), which was inversely correlated with ocular uptake (r = -0.7485, p < 0.0001). A significant reduction in ocular uptake was observed in mice with large tumor burdens (-41.8% at 24 h, -47.4% at 72 h, p = 0.022).

Conclusion

These findings suggest that tumor burden impacts [131I]ICF01012 distribution in non-target organs, with potential clinical implications for dosimetry and toxicity mitigation in radiopharmaceutical therapy for metastatic melanoma. Further studies are needed to refine dosimetric models and assess the translational relevance of this effect in human subjects.

Graphical abstract