RT Journal Article SR Electronic T1 Targeted Imaging of Melanoma for Alpha-Particle Radiotherapy (TIMAR) Trial JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP P378 OP P378 VO 64 IS supplement 1 A1 Johnson, Geoffrey A1 Block, Matthew A1 Hruska, Carrie A1 Pandey, Mukesh A1 Paulsen, Andrew A1 Kemp, Brad A1 Packard, Ann A1 Robert, Murphy A1 Lunn, Brendan A1 Schultz, Michael A1 Dunagan, Kelly A1 Delaney, Kera A1 Johnson, Frances YR 2023 UL http://jnm.snmjournals.org/content/64/supplement_1/P378.abstract AB P378 Introduction: To evaluate two experimental imaging radiopharmaceuticals as diagnostic partners for a theranostic approach to alpha-particle therapy in patients suffering from metastatic melanoma. These radiopharmaceuticals target the melanocortin 1 receptor (MC1R). The primary objectives were safety and tracer biodistribution. Secondary objectives included the suitability of [68Ga]VMT02 PET/CT imaging for patient selection prior to future studies of [212Pb]VMT01 radiopharmaceutical therapy, and [203Pb]VMT01 SPECT/CT imaging for predictive dosimetry of [212Pb]VMT01 radiopharmaceutical therapy.Methods: This was a prospective IRB-approved phase 1 first-in-human trial evaluating the safety and biodistribution of [203Pb]VMT01 for SPECT/CT imaging and [68Ga]VMT02 for PET/CT imaging. The study design included a randomized cross-over of [203Pb]VMT01 SPECT/CT Imaging followed by [68Ga]VMT02 PET/CT Imaging (or vice versa) of patients with stage IV metastatic melanoma. 15 to 25 mCi (555 to 925 mBq) of [203Pb]VMT01 was injected IV with imaging performed at 1 hour, 4 hours and 24 hours, including whole body planar imaging on a GE 670 scanner, and whole body SPECT/CT imaging on a Spectrum Dynamics Veriton 64 scanner. 2.0 to 7.5 mCi (74 to 277 mBq) [68Ga]VMT02 was injected IV and imaging was performed on a Siemens Vision 600 PET/CT dynamically up to 1 hour, then at 2 hours and 3 hours. Patient selection included a positive [18F]FDG PET/CT performed within 30 days of experimental radiopharmaceutical injection. Key FDG-avid melanoma lesions were marked on a [18F]FDG PET/CT, and presented to three experienced Radiologists serving as blinded reviewers. The blinded reviewers compared the [18F]FDG PET/CT to the experimental imaging performed at different time points and scored the scans and key lesions on multiple metrics. Organ and tumor dosimetry calculations were performed. Since [203Pb]VMT01 is a chemically identical surrogate for [212Pb]VMT01 therapy, [203Pb]VMT01 SPECT/CT imaging was used for dosimetry calculations of future alpha-emitting therapy. The trial was overseen by an independent safety review committee (SRC). Safety monitoring included physical exams, laboratory assessments, and ECGs before, during and after therapy with follow-up for 30 days after the last injected experimental radiopharmaceutical. Blood and urine samples were obtained at multiple timepoints for analysis.Results: Six patients were imaged prospectively. No safety issues related to either experimental imaging radiopharmaceutical were identified by the SRC. Blinded reviewers found that 50% of the patients had tumors positive on [68Ga]VMT02 PET/CT imaging (above background liver activity), suggesting they would have been selected as eligible for future [212Pb]VMT01 therapy. [68Ga]VMT02 PET/CT imaging at the 3-hour time point resulted in the best tumor to background conspicuity of the metabolically active melanoma metastases. Dosimetry calculated for [68Ga]VMT01 has lower systemic and organ radiation exposure than [18F]FDG. [203Pb]VMT01 SPECT/CT imaging showed retention of radiopharmaceutical within tumors at 24 hours post injection. Dosimetry for [203Pb]VMT01 showed acceptable radiation exposure.Conclusions: No safety concerns were identified for IV injection of [203Pb]VMT01 or [68Ga]VMT02 into humans. [68Ga]VMT02 PET/CT may be useful for identifying MC1R expression on tumors in patients with metastatic melanoma, allowing for selection for [212]VMT01 alpha-emitting radiopharmaceutical therapy in future studies. [203Pb]VMT01 allowed for calculations of organ and tumor dosimetry for future [212Pb]VMT01 therapy.