New SPECT marker for metastatic melanoma may have therapeutic possibilities

With low survival rates for patients with metastasized melanoma, accurate staging and effective treatments are critical for extending life. Two newly published papers from research teams in France and Germany respectively describe the potential of a newly developed benzamide-based radiopharmaceutical for the imaging of metastases, and potentially as a targeted systemic therapy

(Ref 1. Cachin F et al. 123I-BZA2 as a Melanin-Targeted Radiotracer for the Identification of Melanoma Metastases: Results and Perspectives of a Multicenter Phase III Clinical Trial J Nucl Med. 2014; 55: 15doi: 10.2967.

Ref 2. Mier et al Radiopharmaceutical Therapy of Patients with Metastasized Melanoma with the Melanin-Binding Benzamide 131I-BA52.J Nucl Med. 2014;55 :9doi: 10.2967/)

Malignant melanoma is the fifth most common cancer in men and the sixth most common in women, and its incidence rate is increasing rapidly. It accounts for nearly 80 percent of all deaths in cutaneous cancer. When discovered early, localized melanoma can be cured by surgical removal. However, the cancer displays a strong tendency to metastasize and patients have very low survival rates, with fewer than five percent surviving longer than five years.

The French researchers developed a SPECT radiopharmaceutical for malignant melanoma – called 123I-BZA2. In their study, 87 patients with metastasized melanoma were then examined by both 18F-FDG PET/CT and 123I-BZA2 SPECT to compare accuracy in staging and restaging. The sensitivity of 18F-FDG for diagnosis of melanoma metastases was higher than that of 123I-BZA2 but the specificity of 18F-FDG, was however lower than that of 123I-BZA2. The sensitivity and specificity of 123I-BZA2 for the diagnosis of melanin-positive lesions were 75 percent and 70 percent, respectively.

“We have demonstrated that 123I-BZA2 accumulation in the tumor was clearly correlated to melanin content of the melanoma metastases. Thus, theoretically 123I-BZA2 could be used for the diagnosis of melanoma metastases,” said Dr F Cachin, lead author of the study. “However,  given its low sensitivity due to the high proportion of non-pigmented lesion in of metastatic melanoma, 123I-BZA2 cannot be used for melanoma staging. Such results might appear discouraging, but the concept of melanin targeting may offer a real opportunity for therapy.”

The accompanying paper from the German group describes the first use of the melanoma-seeking agent for therapeutic application. The same BZA2 molecule, first labelled with 123I, was given as a diagnostic isotope to identify patients who could possibly benefit from therapy and then, in the 131I labelled form, as a therapeutic radiopharmaceutical for those patients who would benefit. Twenty-six patients were imaged with 123I-BZA2, and nine patients were selected for therapy with 131I-BA52.

Some of the patients treated with 131I-BA52 were found to have a survival rate of more than two years. “ 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 Dr Uwe Haberkorn, lead author of the study.