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This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Joyal, J. Articles by Babich, J. PubMed Articles by Joyal, J. Articles by Babich, J.

Molecular targeting of melanoma with radiolabeled benzamides

¹ Discovery Research, Molecular Insight Pharmaceuticals, Cambridge, Massachusetts; ² Molecular Imaging Research, Bayer Healthcare, Berlin, Germany

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Objectives: There is no effective therapy for metastatic melanoma. Radiolabeled benzamides are attractive for imaging and radiotherapy as they bind melanin and exhibit high uptake and retention in melanoma. We are developing ¹³¹I-benzamides for targeting melanin-expressing melanoma.

Methods: A series of radioiodinated benzamides were synthesized; MIP-1104, N-(4-(2-(diethylamino)ethylcarbamoyl)-2-iodo-5-methoxyphenyl)benzo[d][1,3]dioxole-5 carboxamide; N-(2-diethylamino-ethyl)-4-(4-X-benzamido)-5-iodo-2-methoxy-benzamide [X = Cl, MIP-1143; OMe, MIP-1144; F, MIP-1145]. Tissue distribution studies compared the uptake and retention of compounds in B16F10 melanoma bearing C57BL6 mice. ¹³¹I-MIP-1145 was further evaluated in melanotic, B16F10, SKMEL3 and amelanotic, A375 cells in vitro, and in vivo to examine the impact of cold carrier on the uptake.

Results: Compounds exhibited similar diffuse tissue distribution and washout from all tissues except the tumor and eye; which both express melanin. Maximal uptake of approximately 15 and 30 %ID/g was seen for tumor and eye, respectively. MIP-1145 was further evaluated as it presents the opportunity for either PET or SPECT. The binding of ¹³¹I-MIP-1145 to melanoma cells in vitro was melanin dependent and increased over time. Cold carrier MIP-1145 reduced uptake only at micromolar concentrations. The addition of cold carrier in vivo did not alter the uptake, retention, or tissue distribution of ¹³¹I-MIP-1145 in either target or non-target tissues.

Conclusions: Radiolabeled benzamides were shown to bind specifically to melanin expressing melanomas both in vitro and in vivo. MIP-1145 may be effective as a molecular diagnostic and radiotherapeutic pharmaceutical for targeting melanoma in patients.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Joyal, J. Articles by Babich, J. PubMed Articles by Joyal, J. Articles by Babich, J.