New diagnostic and therapeutic techniques for patients with metastasized melanoma
With low survival rates for patients with metastasized melanoma, accurate staging and effective treatments are critical to extending life. New research published in The Journal of Nuclear Medicine (2014;55: 9-14 and 15-22) highlights the potential of newly developed radiopharmaceuticals with benzamide for the imaging of metastases and as a targeted systemic therapy.
Malignant melanoma is the fifth most common cancer in men and the sixth most common cancer in women, and its incidence rate is increasing rapidly. It accounts for nearly 80% of all deaths related to cutaneous cancer. When discovered early, localized melanoma can be cured by surgical removal. However, this cancer displays a strong tendency to metastasize and has very low survival rates for patients, with fewer than 5% surviving longer than 5 years.
In the first study, the first use of a melanoma-seeking agent for therapeutic application was analyzed. Researchers used a theranostic approach in which the same molecule was given first as a diagnostic isotope (123I-BA52) to identify the patients possibly benefiting from therapy, and then as a therapeutic radiopharmaceutical (131I-BA52) for those patients who would benefit. Twenty-six patients were imaged with 123I-BA52, and nine patients were selected for therapy with131I-BA52.
Some of the patients treated with 131I-BA52 were found to have a survival rate of more than 2 years. Researchers also found that higher treatment doses would have been tolerated in these patients, as only moderate side effects were observed. “We believe that the tracer could be useful in the setting of a combination therapy in patients with metastasized melanoma, especially when applied in earlier stages of the disease where the melanin production is higher as compared to later stages of the disease,” noted lead author Uwe Haberkorn, MD.
In the second study, researchers developed a specific single photon emission computed tomography (SPECT) radiopharmaceutical for malignant melanoma—123I-BZA2. Imaging of patients with metastasized melanoma was then performed with both 18F-FDG positron emission tomography/computed tomography (PET/CT) and 123I-BZA2 SPECT to compare the accuracy in staging and restaging.
Eighty-seven patients were examined with a total of 86 metastatic lesions. In the analysis of lesions, the sensitivity for 18F-FDG for diagnosis of melanoma metastases was higher than that of 123I-BZA2 (80% vs 23%). The specificity of 18F-FDG, however, was lower than 123I-BZA2 (54% vs 86%). The sensitivity and specificity of 123I-BZA2 for the diagnosis of melanin-positive lesions were 75% and 70%, respectively.
“We have demonstrated that 123I-BZA2 tumor accumulation was clearly correlated to melanin content of the melanoma metastases. Thus, 123I-BZA2 could be theoretically used for the diagnosis of melanoma metastases,” said lead author Florent Cachin, MD, PhD. “However, given its low sensitivity due to the high proportion of nonpigmented lesion in the natural course of metastatic melanoma, 123I- IBZA2 cannot be used for melanoma staging. Such results could appear discouraging, but the concept of melanin targeting may offer a real opportunity for therapy.”