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J Nucl Med. 2008; 49 (Supplement 1):3P
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Cardiovascular: Special Sessions

Herrmann Blumgart Lecture and Award Symposium

Metabolism of 11C-phenethylguanidines

David Raffel1, Yong-Woon Jung1, Guie Gu1, Robert Koeppe1, Phillip Sherman1 and Carole Quesada1

1 Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan

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Objectives: 11C-Phenethylguanidines (11C-PG) are prospective PET tracers for quantifying regional cardiac sympathetic nerve density with compartmental modeling. This study characterized metabolism of several 11C-PG in rats. Also, metabolism of 11C-N-[guanyl]-meta-octopamine (GMO), a promising 11C-PG, was assessed in the rhesus macaque monkey.

Methods: Metabolism of GMO, 11C-p-hydroxy-PG, 11C-m-hydroxy-PG (MHPG), 11C-4-fluoro-MHPG and 11C-6-fluoro-MHPG was studied in rats 30 min after injection of 500 MBq/kg. Plasma and homogenized heart and liver extracts were analyzed using HPLC with radiation detection to measure metabolite and parent tracer fractions. In the monkey, plasma samples (5, 15, 30, 55 min after injecting 75 MBq/kg) were analyzed to determine the time course of GMO metabolism.

Results: In rats, 11C-PG were consistently metabolized into 1 major and 1-3 minor metabolites, all more polar than the parent tracer. Plasma metabolite fractions were similar for all 11C-PG (86-95%). Liver activity was mostly metabolites (96-100%) while heart activity was predominantly parent tracer (97-100%). In monkey, GMO was metabolized with T1/2 ~ 13 min. The major metabolite was less polar than the one in rats, indicating a different metabolism pathway in primates. Applying GMO metabolism data to image-derived input functions from previous microPET studies in monkeys yielded stable model fits (k3 = 0.102 ± 0.024 min–1) and highly linear Patlak slopes (Ki = 0.103 ± 0.021 mL/min/g).

Conclusions: Radiometabolites of 11C-PG are inactive in rats, with only the parent tracers actively taken up by cardiac sympathetic neurons. Application of metabolite corrections to GMO kinetics in monkeys provided encouraging results, supporting the hypothesis that GMO can be used to quantify cardiac sympathetic nerve density in humans.

Research Support: NIH R01-HL079540





This Article
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Raffel, D.
Right arrow Articles by Quesada, C.
PubMed
Right arrow Articles by Raffel, D.
Right arrow Articles by Quesada, C.