Dynamic tracking during intracoronary injection of18F-FDG- labeled progenitor cell therapy for acute myocardial infarction

Brendan Doyle, Brad J. Kemp, Panithaya Chareonthaitawee, Cynthia Reed, Jeffrey Schmeckpeper, Paul Sorajja, Stephen Russell, Philip Araoz, Stephen J. Riederer, Noel M. Caplice

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Abstract

We assessed the feasibility of dynamic 3-dimensional (3D) PET/CT tracking of 18F-FDG-labeled circulating progenitor cell (CPC) therapy during intracoronary injection, using a porcine model of acute myocardial infarction (MI). Methods: Human and porcine CPC were radiolabeled with 18F-FDG, with variation in temperature and incubation time to determine optimal conditions. For in vivo experiments, CPC were harvested before induction of infarction (using 90-min coronary balloon occlusion). At 48 h, animals underwent cardiac MRI to assess infarct size. A balloon catheter was placed in the infarct artery at the same location as that used for induction of MI, and during dynamic 3D PET/CT 3 × 107 autologous 18F-FDG progenitor cells were injected through the central lumen using either (a) 3 cycles of balloon occlusion and reperfusion or (b) high-concentration, single-bolus injection without balloon occlusion (n 5 3 for both protocols). Peripheral blood was drawn at 1-min intervals during cell injection. Results: Labeling efficiency was optimized by 30-min incubation at 37°C (human CPC, 89.9% ± 4.8%; porcine CPC, 91.6% ± 6.4%). Cell-bound activity showed a nonsignificant decrease at 1 h (human, 74.3% ± 10.7%; porcine, 77.7% ± 12.8%; P > 0.05) and a significant decrease at 2 h (human, 62.1% 6 8.9%; porcine, 68.6% ± 5.4%; P = 0.009). Mean infarct size was similar for both injection protocols (16.3% ± 3.4%and 20.6% ± 2.7%; P > 0.05). Dynamic scanning demonstrated a sharp rise in myocardial activity during each cycle of balloon-occlusion cell delivery, with a significant fall in activity (around 80%) immediately after balloon deflation. The latterwas associatedwith a transient spike in peripheral blood 18F-FDG activity, consistent with the first pass of labeled cells in the systemic circulation. A single spike and gradual fall inmyocardial activity was observed with high-concentration, single-bolus therapy. At 1 h, myocardial activity was 8.7% ± 1.5% of total injected dose for balloon-occlusion delivery and 17.8% ± 7.9% for high-concentration, single-bolus delivery (P = 0.08). Conclusion: Dynamic tracking during intracoronary injection of 18F-FDG-labeled CPC is feasible and demonstrates significant cell washout from the myocardium immediately after balloon deflation. High-concentration, single-bolus therapymay be as effective as balloon-occlusion delivery. This tracking technique should facilitate development of improved delivery strategies for cardiac cell therapy.

Original languageEnglish (US)
Pages (from-to)1708-1714
Number of pages7
JournalJournal of Nuclear Medicine
Volume48
Issue number10
DOIs
StatePublished - Oct 1 2007

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Keywords

  • Cell therapy
  • Dynamic PET/CT cell tracking
  • Myocardial infarction

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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