TY - JOUR
T1 - Dynamic tracking during intracoronary injection of18F-FDG- labeled progenitor cell therapy for acute myocardial infarction
AU - Doyle, Brendan
AU - Kemp, Brad J.
AU - Chareonthaitawee, Panithaya
AU - Reed, Cynthia
AU - Schmeckpeper, Jeffrey
AU - Sorajja, Paul
AU - Russell, Stephen
AU - Araoz, Philip
AU - Riederer, Stephen J.
AU - Caplice, Noel M.
PY - 2007/10/1
Y1 - 2007/10/1
N2 - 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.
AB - 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.
KW - Cell therapy
KW - Dynamic PET/CT cell tracking
KW - Myocardial infarction
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U2 - 10.2967/jnumed.107.042838
DO - 10.2967/jnumed.107.042838
M3 - Article
C2 - 17909258
AN - SCOPUS:35348913798
SN - 0161-5505
VL - 48
SP - 1708
EP - 1714
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 10
ER -