The study hypothesis is that new imaging agents [203Pb]VMT01 and [68Ga]VMT02 can be safely used in humans without independent biological effect and can be used to image melanoma tumors expressing the melanocortin sub-type 1 receptor (MC1R) by SPECT/CT and PET/CT imaging modalities respectively.

This is a first-in-human study evaluating the suitability of [203Pb]VMT01 for SPECT/CT imaging and [68Ga]VMT02 for PET/CT imaging of MC1R-expressing metastatic melanoma. Study results will provide foundational data to develop imaging and dosing for future therapeutic trials of [212Pb]VMT01 for the treatment of metastatic melanoma.

The study will be a cross-over study with the participants serving as their own comparator. Participants with positive FDG-PET scans for stage IV (or inoperable stage III) metastatic melanoma will undergo SPECT/CT scans utilizing [203Pb]VMT01 followed a few weeks later by PET/CT scans utilizing [68Ga]VMT02, or vice versa. The order of the imaging agents will be randomly assigned.

Inclusion Criteria:

1. Diagnosed with Stage IV metastatic melanoma, or inoperable Stage III equivalent
2. Baseline fluorodeoxyglucose (FDG)-PET scan available from within 30 days prior to date of enrollment
3. Blood counts and metabolic results within protocol limits within 14 days prior to enrollment
4. Ability to lie flat and still for a minimum of two hours for imaging
5. Male and female participants with reproductive potential must agree to use highly effective contraception in preparation of the study, during the study, and for 4 weeks following the last dose of an investigative imaging agent
6. Documented life expectancy of at least 3 months

Exclusion Criteria:

1. Active secondary malignancy
2. Prior treatment (for any reason) with radioactive nuclides; imaging tracers are acceptable
3. Pregnancy or breast feeding a child
4. Uncontrolled infection
5. Treatment with another investigational drug within 30 days prior to enrollment date
6. Any treatment with BRAF inhibitors since the baseline FDG-PET scan or plans for such treatment during the study
7. Kidney function not within protocol limits
8. BMI>40 kg/m2
9. History of a condition resulting in anaphylaxis or angioedema

All de-identified individual participant data (IPD) that underlies results in a peer-reviewed scientific publication will be shared.

Archived tumor tissue will be tested for expression of the imaging target, melanocortin receptor sub-type 1 (MC1R). The qualified researcher who tests the sample, and the independent pathologist who reviews the results, will be blinded to a participant's identifying information and imaging results. Evaluators will not have access to the medical record.

A pool of three qualified readers will evaluate study images (PET/CT and SPECT/CT). Images and medical information given to the readers will not include a participant's identifying information. The reader pool will not know the sequence of imaging for a participant or have access to the medical record.

An independent medical physicist will validate imaging results and measurements of radiation absorbed and excreted by the participant's body. The physicist will be blinded to participant identifiers and demographics, as well as the sequence of imaging for a participant. The physicist will not have access to the medical record.