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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 Shin, I. Articles by Paik, C. PubMed Articles by Shin, I. Articles by Paik, C.

^99mTc-labeling of _vβ₃-binding antagonist to selectively target _vβ₃ receptor-positive tumor

¹ NMD; ² Radiology, CC, NIH, Bethesda, Maryland

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Objectives: To label _vβ₃ antagonist with ^99mTc to selectively target _vβ₃-expressing tumors.

Methods: The amino terminus of 4-[2-(3,4,5,6-tetrahydropyrimidin-2-ylamino)-ethyloxy]benzoyl-2-(S)-[N-(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonylamino-β-alanine hydrochloride (IAC) was conjugated with N-hydroxysuccinimide ester of HYNIC and was labeled with ^99mTc using tricine and 1,5-pyridinedicarboxylic acid (PDA) as co-ligands. Nude mice (n=5 per time point), implanted with _vβ₃-expressing M21 human melanoma, were injected iv with the ^99mTc labeled product (6.25 µCi/19.4 fmol) and were euthanized at 1, 2, and 4 h. A group of mice was also coinjected with 200 µg of a peptidomimetic antagonist.

Results: The in vitro bindability of the ^99mTc product to _vβ₃ at 0.4 µM was 51.1% which was completely blocked by cold _vβ₃ antagonist. The radiolabel accumulated rapidly in the receptor-positive tumor with 2.40±0.11, 2.13±0.26 and 1.59±0.23% ID/g at 1, 2, and 4 h, respectively. It was excreted via both the renal and hepatobiliary systems with 57.8±5.2% ID retained in the whole-body at 1 h. The whole-body activity remained unchanged up to 4 h due to the major radioactivity retained in the intestine. The coinjection of cold antagonist decreased the tumor uptake to 0.96±0.30% ID/g at 1 h, indicating that the tumor uptake was receptor mediated. The nuclear imaging with ^99mTc-(tricine)(PDA)/HYNIC-IAC visualized tumors located 2 cm from the abdomen at 3 h postinjection.

Conclusions: The HYNIC labeling method, using PDA as a co-ligand, formed ^99mTc labeled IAC that was retained in the receptor-positive tumor while being excreted via both the renal and hepatobiliary systems. It is desirable to synthesize ^99mTc labeled IAC which is rapidly excreted via the renal system to increase the imaging sensitivity in the abdomen.

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 Shin, I. Articles by Paik, C. PubMed Articles by Shin, I. Articles by Paik, C.