Preclinical evaluation of an 131I-labeled benzamide for targeted radiotherapy of metastatic melanoma

John L Joyal, John A. Barrett, John C Marquis, Jianqing Chen, Shawn M Hillier, Kevin P Maresca, Marie Boyd, Kenneth Gage, Sridhar Nimmagadda, James F Kronauge, Matthias Friebe, Ludger Dinkelborg, James B Stubbs, Michael G Stabin, Rob Mairs, Martin G Pomper, John W Babich

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42 Citations (Scopus)


Radiolabeled benzamides are attractive candidates for targeted radiotherapy of metastatic melanoma as they bind melanin and exhibit high tumor uptake and retention. One such benzamide, N-(2-diethylamino-ethyl)-4-(4-fluoro-benzamido)-5-iodo-2-methoxy-benzamide (MIP-1145), was evaluated for its ability to distinguish melanin-expressing from amelanotic human melanoma cells, and to specifically localize to melanin-containing tumor xenografts. The binding of [(131)I]MIP-1145 to melanoma cells in vitro was melanin dependent, increased over time, and insensitive to mild acid treatment, indicating that it was retained within cells. Cold carrier MIP-1145 did not reduce the binding, consistent with the high capacity of melanin binding of benzamides. In human melanoma xenografts, [(131)I]MIP-1145 exhibited diffuse tissue distribution and washout from all tissues except melanin-expressing tumors. Tumor uptake of 8.82% injected dose per gram (ID/g) was seen at 4 hours postinjection and remained at 5.91% ID/g at 24 hours, with tumor/blood ratios of 25.2 and 197, respectively. Single photon emission computed tomography imaging was consistent with tissue distribution results. The administration of [(131)I]MIP-1145 at 25 MBq or 2.5 GBq/m(2) in single or multiple doses significantly reduced SK-MEL-3 tumor growth, with multiple doses resulting in tumor regression and a durable response for over 125 days. To estimate human dosimetry, gamma camera imaging and pharmacokinetic analysis was performed in cynomolgus monkeys. The melanin-specific binding of [(131)I]MIP-1145 combined with prolonged tumor retention, the ability to significantly inhibit tumor growth, and acceptable projected human dosimetry suggest that it may be effective as a radiotherapeutic pharmaceutical for treating patients with metastatic malignant melanoma.
Original languageEnglish
Pages (from-to)4045-4053
Number of pages9
JournalCancer Research
Issue number10
Publication statusPublished - May 2010


  • benzamides
  • drug evaluation
  • iodine radioisotopes
  • macaca fascicularis
  • melanins
  • melanoma
  • neoplasm metastasis
  • radiopharmaceuticals
  • radiotherapy dosage
  • tomography
  • xenograft model antitumor Assays


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