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Theranostic Radiotracers for Melanoma Imaging and Therapy: A Comparative Study of Subcutaneous and Intradermal Tumor
Mirel Cabrera1, Ximena Camacho1, Marcos Tassano1
1Area de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
Abstract:
Introduction: Melanoma, with its aggressive behavior and high metastatic potential, presents significant clinical challenges. The melanocortin-1 receptor (MC1R) is a promising target for diagnosis and therapy due to its overexpression in metastatic melanoma. Methods: This study compares the theranostic potential of DOTARe-CCMSH, labeled with 68Ga and 177Lu, in subcutaneous and intradermal murine melanoma models over an extended period. Radiolabeling achieved high molar activities for both isotopes, enabling precise imaging and therapeutic applications. Results: PET imaging with [68Ga]Ga-DOTA-Re-CCMSH showed specific tumor accumulation, with a mean uptake of 2.25 ± 0.2% ID/g at 2 hours post-injection, enhanced by gelofusine pre-administration. SPECT imaging with [177Lu]LuDOTA-Re-CCMSH revealed significant and sustained tumor uptake in both models, with mean values of 21.9 ± 7.98 for subcutaneous and 19.8 ± 5.36 for intradermal tumors at 4 hours post-injection, extending up to 24 hours. This study tracked the therapeutic radiotracer uptake for up to 7 days post-injection, showing continued retention and tumor specificity, especially in the tumor-to muscle ratio, which reached 172 at 24 hours. Discussion and Conclusions: Comparative biodistribution analyses highlighted differences between subcutaneous and intradermal models, including distinct peritumoral edema arrangements. These findings emphasize the value of long-term theranostic studies in understanding tumor behavior and the efficacy of radiolabeled peptides in melanoma treatment, advancing personalized oncology approaches.
Insights
This study evaluated DOTARe-CCMSH labeled with Gallium-68 and Lutetium-177 for melanoma theranostics. The radiotracer showed specific tumor uptake and retention in preclinical models, supporting its potential for melanoma diagnosis and therapy.
Area of Science:
- Nuclear Medicine
- Oncology
- Radiopharmaceutical Chemistry
Background:
- Melanoma is an aggressive cancer with high metastatic potential.
- The melanocortin-1 receptor (MC1R) is overexpressed in metastatic melanoma, making it a viable diagnostic and therapeutic target.
Purpose of the Study:
- To compare the theranostic potential of DOTARe-CCMSH labeled with Gallium-68 (68Ga) and Lutetium-177 (177Lu) in preclinical melanoma models.
- To evaluate the diagnostic imaging and therapeutic efficacy of these radiotracers over an extended period.
Main Methods:
- Radiolabeling of DOTARe-CCMSH with 68Ga and 177Lu to achieve high molar activities.
- Positron Emission Tomography (PET) imaging using [68Ga]Ga-DOTA-Re-CCMSH in subcutaneous and intradermal murine melanoma models.
- Single-Photon Emission Computed Tomography (SPECT) imaging using [177Lu]LuDOTA-Re-CCMSH in the same models.
- Long-term biodistribution and tumor uptake analysis for up to 7 days post-injection.
Main Results:
- 68Ga-labeled tracer demonstrated specific tumor accumulation (2.25 ± 0.2% ID/g at 2h), enhanced by gelofusine.
- 177Lu-labeled tracer showed significant and sustained tumor uptake (e.g., 21.9 ± 7.98% ID/g at 4h for subcutaneous tumors) up to 24 hours and beyond.
- High tumor-to-muscle ratios (up to 172 at 24h) and prolonged retention indicated tumor specificity.
- Comparative biodistribution revealed differences between subcutaneous and intradermal models, including edema patterns.
Conclusions:
- DOTARe-CCMSH labeled with 68Ga and 177Lu exhibits promising theranostic potential for melanoma.
- Long-term theranostic studies are crucial for understanding tumor behavior and optimizing radiolabeled peptide efficacy.
- These findings support the advancement of personalized oncology approaches for melanoma treatment.
