Detection of melanoma lesions using ¹³¹I-IMBA obtained by electrophilic substitution of ¹³¹I for metal organic substituent - a preliminary communication.

BACKGROUND: Compounds of N-alkylated benzamide derivatives have been the subject of investigations in the last few decades from the standpoint of their possible application for scintigraphic detection of melanoma. Positive results have been observed in studies on biodistribution when using animal models and the compound IMBA (N-(2-diethylaminoethyl)-3-iodo-4-metoxybenzamide). The present study presents preliminary results of scintigraphic studies in patients with documented melanoma metastases, who were administered ¹³¹I-IMBA synthesized by modified labelling procedure (electrophilic substitution of radioactive ¹³¹I to metal organic substituent). MATERIAL AND METHODS: The study was made in three patients with diagnosed melanoma metastases to tissues and organs. To each patient 111 MBq of ¹³¹I-IMBA was intravenously administered and whole body scintigraphy was performed 4 and 24 hours post injection of the radiopharmaceutical. Additionally, after 24 hours, SPECT/CT of selected regions of the body was performed. RESULTS: In 3 patients a total of 20 lesions of increased activity were found (15 were detected previously by other methods, 5 in the head, 4 in thorax, 2 in liver and spleen, 3 in abdomen and 6 in extremities). In the scintigrams performed 4 hours after ¹³¹I-IMBA administration, there were found 12 lesions of enhanced accumulation of the radiopharmaceutical. After 24 hours, due to reduction of background activity, there were 8 additional hot lesions detected. The mean activity tumour/background ratio for 20 lesions 4 hours post injection amounted to 1.51 ± 0.64, and the ratio increased to 2.94 ± 2.32 24 hours after administration of a radiopharmaceutical. CONCLUSIONS: ¹³¹I-IMBA preparation, obtained by a modified labelling procedure, enabled detection of metastatic lesions in the patients. This may indicate that there is a possibility of using radioiodinated IMBA (with ¹²³I or ¹³¹I) for diagnosis of melanoma in humans. From our results it follows that scintigraphy should be performed 24 hours post injection. Further studies on diagnostic efficacy (sensitivity and specificity) of the method are necessary.

The role of radiopharmaceuticals in diagnosis of melanoma malignum.

Melanoma malignum belongs to the group of neoplasms with the highest lethality. Due to the continuous increase of incidence in numerous countries, this malignance has become a serious health problem. This highly aggressive neoplasm is a source of metastases to most organs and eo ipso of bad prognosis. Early detection of the primary tumour and of metastases creates a chance for optimal therapy. The methods of nuclear medicine are becoming more popular in diagnostics of melanomas because they offer advantages over traditional methods of anatomic imaging. Functional imaging, based on the use of modern radiopharmaceuticals frequently offers more successful identification and characterization of malignant neoplasms. Over the last few decades there have been numerous attempts to utilize, in the diagnostics of melanomas, a number of compounds labelled with radioactive nuclides. An accepted role in diagnosis of melanoma found a technique of lymphoscintigraphic mapping of lymphatic nodes and of detection of the sentinel node. In addition, modern positron emission tomography (PET) with use of (18)F-fluorodeoxyglucose has found acceptance in melanoma diagnostics. The present review refers to information on the presently used and potential new radiopharmaceuticals promising effective melanoma diagnostics.

Biodistribution of two (131)I-IMBA preparations, differently labelled, in mice with experimental B16 melanoma tumours.

BACKGROUND: Numerous reports indicate that some iodinated compounds of benzamide derivatives display a strong affinity to the cells of melanoma. In the present report, a compound [N-(2-diethylaminoethyl)-3-iodo-4metyoxybenzamide ((131)I-IMBA)] has been prepared by two different labelling methods. Biodistribution of the injected compound was followed in mice with experimentally induced B16 melanoma tumours, and tumour/ tissue ratios were studied as a function of time post administration. MATERIAL AND METHODS: The iodinated (131)I-IMBA was obtained by means of (131)I exchange for nonradioactive iodine atoms (method I) and by means of (131)I substitution for a metalorganic group (method II). The last preparation was purified by chloroform extraction. The chemical purity was assessed by means of ascending thin layer chromatography (TLC). The biodistribution of (131)I-IMBA in C57 Black mice was studied in animals with experimentally induced B16 mice melanoma tumours. RESULTS: The mean labelling efficiency exceeded 95 and 80 % for methods I and II, respectively, at radiochemical purity > 95% in both cases. (131)I-IMBA was vividly cumulated by melanoma tumours in mice. At 24-hours post (131)I-IMBA administration the values of tumour /non-tumour ratios for the compound labelled by method II reached the following values: tumour/liver 10 +/- 3, tumour/lung 15 +/- 12, tumour/blood 153 +/- 39, tumour/intestines 176 +/- 26, tumour/kidneys 270 +/- 107, and tumour/muscle 448 +/- 82. These values exceeded, by an order of magnitude, the corresponding ratios for the same compound labelled by method I. CONCLUSIONS: High values of tumour/non-tumour ratios indicate that (131)I-IMBA could be a promising radiopharmaceutical for clinical diagnosis (staging) of melanomas in humans.