RT Journal Article SR Electronic T1 68Ga-Galmydar: PET Imaging of Myocardial Infarction in Rabbits & Comparative Blood Flow Analysis in Rat JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 3126 OP 3126 VO 61 IS supplement 1 A1 Jothilingam Sivapackiam A1 Richard Laforest A1 Vijay Sharma YR 2020 UL http://jnm.snmjournals.org/content/61/supplement_1/3126.abstract AB 3126Objectives: Myocardial Perfusion Imaging (MPI) plays an important role in the noninvasive assessment of Coronary Artery Disease (CAD). For wider deployment of PET imaging resources to enable quantitative detection of CAD, 68Ga-Galmydar, an ultrasensitive and specific transport substrate of Pgp (ABCB1) and BCRP (ABCG2), shows rapid uptake and sustained retention within myocardium of mice, rats and rabbits. To further demonstrate its potential in models of CAD, we show ability of 68Ga-Galmydar to image macro-infarction and transient-infarction defects in rabbit models and show preliminary assessment of its response to adenosine stress. Methods: 68Ga-Galmydar and non-radiolabeled counterparts were synthesized from Schiff base precursor ligands, purified on a C-18 column, using radio-HPLC, and employed for PET/MRI imaging studies in normal and in left coronary artery ligated rabbits. After PET/MRI imaging, Evans blue dye in saline solution was injected, the harvested hearts were sliced along the short axis (2 mm thickness). Slices were incubated in 1% triphenyltetrazolium chloride (TTC) in PBS at 37°C for 20 minutes and then fixed in 10% PBS-buffered formalin for overnight at 4°C, and photographed with a high resolution digital camera. To evaluate ability of 68Ga-Galmydar to respond to adenosine stress in rat models, comparative analysis with 13N-NH3 under identical conditions was performed. Results: To evaluate ability to detect perfusion defects, 68Ga-Galmydar was administered intravenously following a ligation of the left anterior descending (LAD) coronary artery in rabbits. In the dynamic PET/MRI images, while 68Ga-Galmydar shows uptake and retention in normal heart accompanied by faster clearance from blood, liver, and lung, the radiopharmaceutical did not indicate uptake in either permanent or transient infarcted regions of the rabbit heart indicating its ability to monitor macro- and transient perfusion defects. These data also correlated with histochemical staining post-imaging. Imaging experiments at rest were separated from those of stress by 4h (68Ga-Galmydar) and 1h (13N-NH3) and residual activity from rest experiments was subtracted from those of stress experiments for quantification. From dynamic PET imaging data, image-derived time-activity were used to delineate the arterial input and myocardial response curve for tracer kinetic modeling to calculate MBF in ml/min/g. For kinetic modeling, while one-compartment model was used for 68Ga-Galmydar, similar to other mitochondrial targeted probes, the 2-compartment model was deployed for 13N-NH3 and absolute MBF was determined as a function of increasing dose of adenosine stress. 68Ga-Galmydar showed response to adenosine-induced pharmacological stress similar to that of 13N-NH3. Using Graph pad prism, the linear regression analysis of MBFs measurement data for two radiotracers indicated a slope of 1.048±0.072. Conclusions: 68Ga-Galmydar, a transport substrate of Pgp and BCRP, demonstrates ability to image acute and transient myocardial infarction defects in rabbits and quantify response to pharmacological stress (similar to that ammonia) in rats. References: Sivapackiam, J. et. al. Nucl. Med. Biol 2016, 43, 191; Sharma, V. et. al. PlosOne 2014, 9, e109361; Sivapackiam, J. et. al. Dalton Transactions, 2010, 39, 5842; Sharma, V. J. Nucl. Med. 2005, 46, 354; Bioconjugate Chem 2004, 15, 1464. Funding: NIH RO1HL111163 (VS), R33AG033328 (VS), American Health A2007-383(VS)