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Tumor sink effect on melanin-ligand [131I]ICF01012 in melanoma and its implications for targeted radionuclide therapy
Elodie Jouberton1,2,3, Sophie Besse4, Tommy Billoux4,5,6
1Service de Médecine Nucléaire, Centre Jean Perrin, Clermont-Ferrand, France. elodie.jouberton@clermont.unicancer.fr.
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.
Insights
Tumor burden significantly affects the distribution of [131I]ICF01012, a melanin-targeting radiopharmaceutical. Increased tumor uptake in metastatic melanoma correlates with reduced uptake in organs like the eyes.
Area of Science:
- Radiopharmaceutical research
- Oncology
- Melanoma diagnostics
Background:
- The tumor sink effect describes radiopharmaceutical sequestration by tumors, impacting non-target organ bioavailability.
- This effect is known in various cancers but unstudied for melanin-targeting agents in metastatic melanoma.
- [131I]ICF01012 targets melanin and shows high ocular uptake, prompting investigation into tumor burden influence.
Purpose of the Study:
- To investigate the impact of tumor burden on the biodistribution of [131I]ICF01012 in metastatic melanoma.
- To assess if tumor volume influences radiopharmaceutical uptake in organs at risk, specifically the eyes.
Main Methods:
- Ex vivo biodistribution study in syngeneic murine melanoma models (B16-F10, B16-OVA, B16BL6).
- Correlation of tumor volume with [131I]ICF01012 uptake using gamma counting.
- Analysis of radiopharmaceutical distribution in non-target organs, particularly the eyes.
Main Results:
- Significant tumor uptake of [131I]ICF01012 was observed (18.8 ± 4.5 IA%/g at 24 h).
- Tumor uptake was inversely correlated with ocular uptake (r = -0.7485, p < 0.0001).
- Mice with large tumor burdens showed significantly reduced ocular uptake (-41.8% at 24 h, -47.4% at 72 h).
Conclusions:
- Tumor burden influences the biodistribution of [131I]ICF01012 in metastatic melanoma.
- Findings suggest potential clinical implications for dosimetry and toxicity mitigation in radiopharmaceutical therapy.
- Further research is needed to refine dosimetric models and assess translational relevance in humans.
