TY - JOUR T1 - <strong>Proinflammatory cytokines lower <sup>99m</sup>Tc sestamibi retention and enhance the washout in isolated cardiomyocytes</strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 107 LP - 107 VL - 59 IS - supplement 1 AU - Luciano Oliveira AU - Marcus Simoes AU - Denise Hilfiker-Kleiner AU - Melanie Ricke-Hoch AU - Frank Bengel AU - James Thackeray Y1 - 2018/05/01 UR - http://jnm.snmjournals.org/content/59/supplement_1/107.abstract N2 - 107Purpose: 99mTc-Sestamibi is a myocardial perfusion tracer with prolonged myocardial retention due to mitochondrial binding. Inflammmation can affect mitochondrial function, which may in turn alter the kinetics of 99mTc-sestamibi. We investigated the effects of pro-inflammatory cytokines on uptake and retention of 99mTc-sestamibi in isolated cardiomyocytes and fibroblasts. Methods: Neonatal rat cardiomyocytes (NRCM) and fibroblasts (NRFB) were isolated and maintained in optimal culture medium. After equilibration, cells were stimulated by increasing concentrations of interferon-γ (5, 10 or 25 ng/mL) or vehicle for 24 or 48 hours. 99mTc-Sestamibi was added to the medium and incubated for 30min. Supernatant activity was measured at 30min, 90min, and 240min to determine tracer washout. Total retention was measured at 240min in cell lysate. All counts were normalized to protein content. Cell viability after treatment was assessed using 18F-deoxyglucose uptake. Results: Control NRCM showed a normalized 99mTc-sestamibi retention of 1.7±0.5% injected dose (ID) at 30min and 0.6%ID at 240min. Stimulation with IFN-γ over 24h resulted in modestly decreased tracer uptake at 30min (25ng/ml, 1.3±0.5%ID, p=0.06) and significantly lower retention at 90min compared to control NRCM (%ID, 0.8±0.4 vs 1.1±0.4, p=0.04). Consistently, washout was accelerated compared to control (%, 90min: 38±10 vs 32±6, p=0.06; 240min 72±5 vs 68±5, p=0.04). Longer pro-inflammatory stimulation resulted in modest NRCM hypertrophy. 99mTc-Sestamibi uptake was further decreased compared to matched control NRCM (%ID, 30min: 1.4±0.1 vs 1.7±0.2, p= 0.08; 90min: 0.6±0.1 vs 0.9±0.3, p=0.003; 240min: 0.2±0.1 vs 0.4±0.3, p=0.001), while washout rate was higher (%, 90min: 57±5 vs 45±7, p=0.003; 240min: 86±3 vs 75±12, p=0.026). Decreased retention and elevated washout were also observed with low and intermediate doses of IFN-γ. By contrast, inflammatory cytokines affected neither retention nor washout in NRFB. 18F-Deoxyglucose displayed similar uptake between IFN-γ stimulated and control cells, supporting maintained viability. Conclusion: Cardiomyocyte stress induced by inflammatory cytokines lowers retention and enhances washout of 99mTc-sestamibi in culture, likely reflecting mitochondrial dysfunction. These findings suggest that kinetics of 99mTc-sestamibi may be sensitive to inflammation, and should be considered when interpreting myocardial perfusion images. ER -