RT Journal Article SR Electronic T1 Production of Multimeric Prostate-Specific Membrane Antigen Small-Molecule Radiotracers Using a Solid-Phase 99mTc Preloading Strategy JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1379 OP 1389 DO 10.2967/jnumed.107.040303 VO 48 IS 8 A1 Preeti Misra A1 Valerie Humblet A1 Nadine Pannier A1 Wolfgang Maison A1 John V. Frangioni YR 2007 UL http://jnm.snmjournals.org/content/48/8/1379.abstract AB Small-molecule ligands specific for prostate-specific membrane antigen (PSMA) have the potential to improve prostate cancer imaging. However, highly charged ligands are difficult to label with 99mTc and to purify. In this study, we present an adamantane-trimerized small molecule that has nanomolar binding to PSMA and also has 12 negative charges. Methods: To convert this molecule into a clinically viable SPECT diagnostic, we have developed a simple, cartridge-based, solid-phase prelabeling strategy that, within 25 min, converts readily available and inexpensive 99mTc-pertechnetate into a chemically pure complex, with a reactive N-hydroxysuccinimide (NHS) ester, in neat organic solvent. This stable intermediate can label any amine-containing small molecule or peptide with 99mTc in 1 step, with high specific activity and without the need for high-performance liquid chromatography (HPLC). Results: Solid-phase conversion of 99mTc-pertechnetate to 99mTc-MAS3-NHS (MAS3 is S-acetylmercaptoacetyltriserine) could be completed in 25 min, with >99% radiochemical purity and with no coligands present. This intermediate was then conjugated to adamantane-trimerized GPI (2[(3-amino-3-carboxypropyl)(hydroxy)(phosphinyl)-methyl]pentane-1,5-dioic acid) in 1 step with >95% yield and no need for HPLC purification. The final molecule bound specifically to living human tumor cells expressing PSMA on their surface. Quantitative comparison was made among GPI monomer, GPI trimer, and their 99mTc-derivatives. Conclusion: Our study describes a simple cartridge-based conversion of 99mTc-pertechnetate to a useful, preloaded NHS ester intermediate that takes only 25 min to prepare and results in >99% radiochemical purity. Using this chemistry, we produced a high-specific-activity, 99mTc-labeled, PSMA-targeted small molecule and demonstrate γ-ray radioscintigraphic imaging of living human prostate cancer cells.