Efficacy of Targeted Radionuclide Therapy Using [¹³¹I]ICF01012 in 3D Pigmented BRAF- and NRAS-Mutant Melanoma Models and In Vivo NRAS-Mutant Melanoma.

ABSTRACT:

Purpose

To assess the efficiency of targeted radionuclide therapy (TRT), alone or in combination with MEK inhibitors (MEKi), in melanomas harboring constitutive MAPK/ERK activation responsible for tumor radioresistance.

Methods

For TRT, we used a melanin radiotracer ([¹³¹I]ICF01012) currently in phase 1 clinical trial (NCT03784625). TRT alone or combined with MEKi was evaluated in three-dimensional melanoma spheroid models of human BRAF^V600E SK-MEL-3, murine NRAS^Q61K 1007, and WT B16F10 melanomas. TRT in vivo biodistribution, dosimetry, efficiency, and molecular mechanisms were studied using the C57BL/6J-NRAS^Q61K 1007 syngeneic model.

Results

TRT cooperated with MEKi to increase apoptosis in both BRAF- and NRAS-mutant sphero

SUBMITTER: Akil H 

PROVIDER: S-EPMC8003594 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature