A radiolabelled iodobenzamide for malignant melanoma staging.

123I-N-(di-ethylamino-2-ethyl) 4 iodobenzamide (I-BZA) has been put forward by the Clermont-Ferrand INSERM U71 group (France) as a tracer for malignant melanoma. We report on the clinical results obtained in 56 studies performed on 48 patients. Whole body scans along with spot views were obtained after injection of 185 MBq of I-BZA. The scans were read by three independent observers and correlated to the clinical findings and the other imaging modalities available, taking into account all lesions larger than 1 cm. Patients were classified into two groups on the basis of a post-treatment survey of patients: group I, in complete remission (24 scans); group II: documented metastases (32 scans). In group 1, 21 studies were truly negative. However, three studies showed positive results. Only one turned out to be a false positive (specificity 95%), the other two revealed unknown lesions and modified the patients' management. In group II, 73% of the known metastases were detected with higher sensitivities (> 80%) for eye and orbit, lung and abdomen. One false positive was reported and four new lesions were detected. I-BZA scintigraphy has the same sensitivity as immunoscintigraphy with higher specificity and without the risk of xenoimmunization. It is a useful tool for staging malignant melanoma which can improve patient management.

Phase II scintigraphic clinical trial of malignant melanoma and metastases with iodine-123-N-(2-diethylaminoethyl 4-iodobenzamide).

Preclinical studies established [125I]-N-(2-diethylaminoethyl) 4-iodobenzamide (BZA) as a potential radiopharmaceutical in the management of patients with malignant melanoma. External detection of both murine and human melanotic melanomas was possible after intravenous injection of 125I-BZA in tumor-bearing mice. This article reports a Phase II clinical trial evaluating 123I-BZA as an imaging agent of primary melanomas and metastases. A total of 110 patients with a history of melanoma were investigated in two nuclear medicine departments. Subjects were imaged from 20 to 24 hr after the intravenous injection of 3.5 mCi (130 MBq) of 123I-BZA. After injection, no short-term or long-term side effects were noted. Calculated on a lesion-site basis, diagnostic sensitivity was 81%, accuracy was 87% and specificity was 100%. The melanoma nature of previously occult lesions was confirmed by clinical criteria and/or additional investigations in follow-up studies. The scintigraphies were normal in 44 patients in clinical remission after treatment of malignant melanoma and in seven patients with nonmelanoma disease. No false positive results were observed. Iodine-123-BZA scintigraphy appears to be a safe and useful agent for the detection and follow-up of patients with malignant melanoma. BZA also allowed the detection of unsuspected lesions and the evaluation of the results of various therapeutic procedures such as surgery, chemotherapy, immunobiology, biological therapy or radiotherapy.

Synthesis and evaluation of new iodine-125 radiopharmaceuticals as potential tracers for malignant melanoma.

The synthesis, labeling, and biodistribution of four 125I radiopharmaceuticals designed to localize in melanoma were tested. Uptake in tumors was demonstrated by autoradiography of whole-body sections and quantitated by measurement of radioactivity of selected tissues and tumors using melanoma-bearing mice. N-(2-diethylaminoethyl)-4-iodobenzamide was selected for its highest melanoma uptake: 60 min after IV injection of 6.5% and 4% ID/g, respectively for murine B16 and human melanotic melanoma. Tumor uptake showed the highest values of all analyzed tissues from 6 to 24 hr after injection. High uptake in melanotic tumor tissue with relatively low uptake in blood, muscle, brain, lung, and liver tissue resulted in high tumor/nontumor ratios (at 24 hr for B16, tumor/blood = 37, tumor/brain = 147, tumor/muscle = 95). This agent was compared with iodoamphetamine. Scintigraphic images of the tumor confirmed that external detection of melanoma is possible with this new radiopharmaceutical.