Radioimmunotherapy targets metastatic melanoma lesions in phase I trial

July 1, 2008

NEW YORK (Reuters Health) - Promising findings from a phase I clinical trial indicate that melanin-binding monoclonal antibody labeled with rhenium-118 safely and effectively targets metastatic melanoma soft tissue lesions, investigators reported at the Society for Nuclear Medicine Annual meeting held in New Orleans.

In animal models of metastatic melanoma, "radioimmunotherapy prolonged survival and practically eliminated tumors, leaving only melanin in their place," Dr. Ekaterina Dadachova told Reuters Health.

Dr. Dadachova and Dr. Arturo Casadevall and colleagues at Albert Einstein College of Medicine, Bronx, New York, developed the anti-melanin IgM (PTI-6D2) labeled with 188-Re, which targets extracellular melanin released from dead melanotic tumor cells.

"188-Re is less toxic and more effective than other isotopes currently used in clinical practice," Dr. Dadachova explained. Its half-life of 17 hours is shorter than that of yttrium-90 (2.8 days) and iodine-131 (8 days). Because it is a combined beta and gamma emitter, it has a long emission range, required to reach and kill viable tumor cells that are spatially separated from where extracellular melanin is deposited.

Pain Therapeutics, Inc. has licensed PTI-6D2 from Albert Einstein College and sponsored a phase I trial conducted at Hadassah Medical Center in Jerusalem, which was completed in June.

The 12 study participants had stage IV metastatic melanoma, with lesions in soft tissues (lungs, skin, lymph nodes, stomach), liver and pancreas, detected by 18FDG positron emission tomography and computed tomography 1 week prior to treatment. One patient also had lesions metastasized to the bone, Dr. Dadachova noted. All of the patients had failed other treatments.

Groups of three patients were injected with escalating doses of antibody (0, 10, 20, 50 mg) labeled with 10 mCi 118-Re.

Whole body planar scintigraphy followed by single photon emission computed tomography combined with computed tomography (SPECT/CT) of the area of interest was performed immediately and three more times during the next 24 hours.

According to their meeting abstract, the normal biodistribution of the radiolabeled antibody was visible in the liver, spleen, kidneys, and bladder for up to 24 hours post-injection on planar scintigraphy.

SPECT/CT visualized uptake of 188-Re-PTI-6D2 in soft tissue metastases but not in bony lesions.

"Results showed that PTI-6D2 was capable of localizing in tumor with practically no side effects," Dr. Dadachova said.

Pain Therapeutics, Inc. is now planning phase II trial of 118Re-labeled PTI-6D2 for metastatic melanoma.