PET imaging of myocardial blood flow in the stressed mouse heart in vivo

1635 Objectives To measure absolute myocardial blood flow (MBF) in mouse heart using 13N-ammonia dynamic PET imaging and test the hypothesis that inhibition of glucose regulated mTOR activity by rapamycin will improve MBF in the pressure overload stressed mouse heart in vivo. Methods MBF was measured at rest and during vasodilator stress by dynamic 13N-ammonia PET imaging. 10 min image acquisition was initiated prior to the administration of 800 µCi 13N-ammonia via tail-vein. 10 min after the rest scan, a bolus of regadenoson (2.5 ug/kg in 50 uL) was injected i.v. 2 min later, when heart rate had increased to ≥ 600 bpm, a second 10 min PET scan was initiated followed by injection of another dose of 13N-ammonia. An improved 3-compartment model was used to compute MBF from the dynamic data sets. Myocardial flow reserve (MFR) was computed as the rest:stress flow ratio. MBF was also measured in 5 C57BL/6 male mice at baseline and on day 1 post transverse aortic constriction (TAC) surgery, with or without rapamycin treatment, by dynamic PET. Capillary density was calculated in excised hearts by counting the number of CD31pos cells/mm2 and mTOR activity was measured by pS6 staining at baseline and on day 1 post-TAC. Results In control hearts, MBF increased from 4.8 mL/min/g at rest to 8.9 mL/min/g during vasodilator stress (MFR = 1.9). In TAC mice, there was a 8.3-fold increase in mTOR activity on day 1 without rapamycin treatment whereas with treatment this increase was blunted (2.4X baseline) and MBF was higher than in untreated mice (4.9 vs 3.4 mL/min/g, respectively). Capillary density was 114.8/mm2 at baseline and was 91.9/mm2 on day 1 post-TAC. However, consistent with the higher MBF, capillary density was also higher (100.7/mm2) in treated mice. Conclusions An improved tracer kinetic model can quantitatively measure MBF and MFR in mouse heart using 13N-ammonia dynamic PET imaging in vivo. Rapamycin inhibited mTOR activity, increased capillary density and MBF in the pressure overload stressed mouse heart. Research Support NIH R21HL102627 (to BKK)