Abstract 17405: Biodistribution, Dosimetry, and Specificity of A 99m Tc-Labeled Matrix Metalloproteinase Targeted Radiotracer ( 99m Tc-RP805) for Myocardial Infarct Imaging

Abstract

Introduction: Activation of matrix metalloproteinase (MMPs) post myocardial infarction (MI) predicts post-MI remodeling. MMP activation in the heart can be detected using 99mTc-RP805 a radiolabel peptidomimetic that binds to the catalytic site. The purpose of this study was to evaluate the biodistribution, dosimetry, and specificity of clinical grade 99mTc-RP805 for first-in-human studies. Methods: Male and female rats (n=24) were injected with 99m Tc-RP805 and euthanized at 1, 3, 7 or 12 hr post injection to determine biodistribution and estimate human dosimetry. Organ activity (%ID/g) was used to estimate whole body and organ effective dose using OLINDA. MI was induced in rats by LAD ligation (n=19) and injected with 99m Tc-RP805 3 days post MI, and rats were euthanized 3 hr after injection in absence (n=9) or presence (n=10) of a 100 x blocking dose of RP805 (257 ug/kg) 30 min prior to radiotracer injection to establish specificity. In vivo SPECT/CT imaging was performed with GMP grade 99m Tc-RP805 in rats post-MI (n=4). Results: The %ID/g for each organ is presented per time point (Fig 1 A). The highest radiation dose was found in male kidneys at 3 hr (%ID/g: 6.11 ± 0.54), female kidneys at 1hr (%ID/g: 6.31 ± 0.88). The estimated total body dose for human males was calculated at 0.172 mSv/mCi and 0.283 mSv/mCi for females, equaling a dose of 3.4 mSv and 5.7 mSv for a 30 mCi injection in males and females, respectively. There is 4 fold increase 99mTc-RP805 uptake in the infarct area compared to the normal LV (Fig 1B) and uptake was blocked with cold compound (ANOVA, p<0.001). In vivo SPECT/CT imaging with a newly synthesized GMP compound demonstrates uptake in the anterior LV (Fig 1C). Conclusions: We have developed and evaluated clinical grade 99m Tc-RP805 for targeted MMP imaging post-MI and demonstrated favorable dosimetry, biodistribution, and specificity for first-in-human imaging.