| Background and ObjectiveCardiovascular disease, CVD, has been one of the main cause of death and disability worldwide. As one critical and emergent disease of the CVD, the incidence of myocardial infarction (MI) is growing yearly. Myocardial remodeling which is an important part of the pathophysiological procedure for MI, has great influence on the prognosis for MI patients. Though a variety of anti-myocardial remodeling drugs has been used to inhibit myocardial remodeling clinically, there are no effective measures to evaluate drugs’therapeutic efficiency, and make the individualized decision to choose drugs clinically.The integrin alpha(v)beta(3) receptor imaging has been an important method to evaluate post-MI myocardial remodeling. This study aims at compare the efficacy of different anti-myocardial remodeling drugs through 68Ga-NOTA-PRGD2 PET/CT for MI patient and for MI rat models.MethodThis clinical trial was approved by the ethics committee of Chinese Academy of Medical Sciences and Peking Union Medical College Hospital. All the patients signed the informed consent. A total of 24 MI patients were enrolled (M 19, F 5,39-82y) and they received the breast 68Ga-PRGD2 PET/CT scan 3 days to 2 years after the heart attack.68Ga-PRGD2 was synthesized immediately before the injection with the radiochemical purity more than 97%. Each patient was intravenously injected with the 68Ga-PRGD2 solution at a dose of approximately 0.05mCi per kilogram body weight. Thirty minutes later, a breast scan (one 5-minute bed position) was performed following a low-dose CT scan for attenuation correction and anatomic location.18F-FDG PET/CT study were performed within 48 hours after the 68Ga-PRGD2 imaging.50min after intravenous injection of 18F-FDG at a dosage of 0.15mCi per kilogram body weight, the low-dose CT scan and PET scanning were performed using the same scanning parameters as the 68Ga-PRGD2 PET/CT imaging. The 68Ga-PRGD2 and 18F-FDG PET/CT images were transferred to a workstation (MMWP, Siemens Medical Solution) for comparison and analysis. The co-registered and matched images were visually and semi-quantitatively analyzed. In semi-quantitative analysis, the peak standardized uptake values (pSU Vs) of the Ga-PRGD2 accumulation were measured by obtaining the mean value of a region-of-interest (ROI) setting at the 80% threshold of a lesion. The mean values of normal myocardium were measured as background and the lesion to background ratios were calculated. The comparison of MI patients treated with different drugs was analyzed through Mann-Whitney U test using SPSS. The difference may be statistically significant with the P value below 0.05. The MI rat models built by coronary artery occlusion were randomized into 2 groups:ACEI group(4 rats) and ARB group(4 Tats>. They were-all-underwent 68Ga-PRGD2 microPET imaging during the first 72 hours of occlusion. After drug administration, the rats underwent 68Ga-PRGD2 microPET imaging again in 48 hours. The comparison of MI rats was analyzed through Mann-Whitney U test using SPSS as well.ResultsNormal heart was void of 68Ga-PRGD2 uptake. By referring to the matched 18F-FDG images, the 68Ga-PRGD2 uptake was found at or around the MI regions in 18 MI patients with pSUVs of 1.86±0.60, which was significantly higher than the mean SUVs of the contrast (0.98±0.25) and the lesion to contralateral background ratios were 1.90±0.25.Five of 6 patients whose imagining results were negative were remote infarction. In addition, for three follow-up patients, all of them had decreased 68Ga-PRGD2 uptake. Using Mann-Whitney U test for analyzing, the patients after administration of ACEIs had no difference with those treated with ARBs(P=0.573>0.05).The results from MI rat models were in accordance with those from MI patients.68Ga-PRGD2 uptake was found at the blood-support region of anterior descending branch on the microPET imaging.After the administration of ACEI/ARB drugs, the uptake decreased. Besides, there was no difference between two groups as the P value was above 0.05.ConclusionThe integrin alpha(v)beta(3) receptor imaging method using 68Ga-PRGD2 PET/CT seems reliable for evaluation of prognosis by providing information related to myocardial remodeling. The success of this pilot study merits further clinical investigation of 68Ga-PRGD2 PET/CT in evaluation of anti-myocardial remodeling drug.
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