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J Nucl Med. 2008; 49 (Supplement 1):99P
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Radiopharmaceutical Chemistry: New Chemistry-Oncology

New Chemistry-Oncology II: Small Molecules

[123I]-MIP-1095 for targeting prostate cancer via prostate specific membrane antigen (PSMA): A high specific activity radiosynthesis

Frank Femia1, Kevin Maresca1, Shawn Hillier1, John Marquis1, Eduard Luss-Lusis1, Craig Zimmerman1, John Joyal1, Brian Abeysekera1, James Kronauge1 and John Babich1

1 Molecular Insight Pharmaceuticals, Inc., Cambridge, Massachusetts

393

Objectives: The radiosynthesis affording [123I]-MIP-1095 ([123I]-(S)-2-(3-((S)-1-carboxy-5-(3-(4-iodophenyl)ureido)pentyl)ureido)pentanedioic acid), a novel molecular imaging pharmaceutical for the detection of prostate cancer was optimized to prepare the desired product in high RCY, RCP, and SA on a 250 mCi scale.

Methods: Radioiodination of the trimethyltin MIP-1095 tri-t-butyl ester precursor with Na123I followed by deprotection of the t-butyl ester groups afforded [123I]-MIP-1095. Production of [123I]-MIP-1095 in high RCY, RCP, and SA was achieved through optimization of pH, reaction time, and method of purification. The use of C18 Sep-Pak (SP) for the purification of [123I]-MIP-1095 was investigated. RCY, RCP, and SA were determined by HPLC. LNCaP cell binding was used to confirm the effect of SA of the final product.

Results: Radioiodination of MIP-1095 was most efficient at a pH range of 1-2 with a reaction time of 10 min. Longer reaction times resulted in decomposition of the trimethyltin precursor. Deprotection of the t-butyl ester groups occurred in 35 min, after which degradation of MIP-1095 occurred. Purification was accomplished by employing C18 SP to remove the remaining tin precursor and inorganic salts, followed by a second C18 SP which removed the biologically active des-iodo analog, MIP-1111 ((S)-2-(3-((S)-1-carboxy-5-(3-phenylureido)pentyl)ureido)pentanedioic acid), that formed during the process.

Conclusions: Optimization of the radioiodination and purification procedure for the synthesis of [123I]-MIP-1095 yielded drug product with high RCY, RCP, and SA. This procedure shall be utilized in the manufacturing of [123I]-MIP-1095 to support phase I clinical trials.





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Right arrow Articles by Femia, F.
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Right arrow Articles by Babich, J.