Evaluation of [11C]hemicholinium-15 and [18F]hemicholinium-15 as new potential PET tracers for the high-affinity choline uptake system in the heart

Mingzhang Gao, Michael A. Miller, Timothy R. DeGrado, Bruce H. Mock, John C. Lopshire, Joshua G. Rosenberger, Cristian Dusa, Mithilesh Kumar Das, William J. Groh, Douglas P. Zipes, Gary D. Hutchins, Qi Huang Zheng

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[11C]Hemicholinium-15 ([11C]HC-15) and [18F]hemicholinium-15 ([18F]HC-15) have been synthesized as new potential PET tracers for the heart high-affinity choline uptake (HACU) system. [11C]HC-15 was prepared by N-[11C]methylation of the appropriate precursor, 4-methyl-2-phenyl-morpholin-2-ol, using [11C]CH3OTf in 55-70% radiochemical yield decay corrected to end of bombardment (EOB) and 2-3 Ci/μmol specific activity at end of synthesis (EOS). [18F]HC-15 was prepared by N-[18F]fluoromethylation of the precursor using [18F]FCH2OTf in 20-30% radiochemical yield decay corrected to EOB and >1.0 Ci/μmol specific activity at EOS. The biodistribution of both compounds was determined in rats at 20 min post-intravenous injection, and the results show the heart region uptakes 1.32 ± 0.75%ID/g in R-ventricle for [11C]HC-15 and 1.28 ± 0.81%ID/g in L-ventricle for [18F]HC-15, respectively. The dynamic PET imaging studies of [11C]HC-15 in rats were acquired 60 min post-intravenous injection of the tracer using the IndyPET-II scanner. For the blocking experiments, the rats were intravenously pretreated with 3.0 mg/kg of unlabeled HC-15 prior to [11C]HC-15 injection. [11C]HC-15 rat heart PET studies show rapid heart uptake to give clear heart images. The rat heart PET blocking studies found no significant blocking effect. The dynamic PET studies in normal and ablated dogs were performed using Siemens PET scanner with [13N]NH3, [11C]HC-15, and [18F]HC-15. PET studies in dogs of both [11C]HC-15 and [18F]HC-15 also show significant heart uptake and give images of the heart. However, there is no significant change in [11C]HC-15 L-ventricle uptake following radiofrequency ablation in the dog. These results suggest that the localization of HC-15 tracers in the heart is mediated by non-specific processes, and the visualization of HC-15 tracers on the heart is related to non-specific binding of HACU.

Original languageEnglish (US)
Pages (from-to)1289-1297
Number of pages9
JournalBioorganic and Medicinal Chemistry
Issue number3
StatePublished - Feb 1 2007

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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