RESULTS: The decay-corrected yields of [11C]MMP at the end of synthesis were 41.4 ± 6.5%, with 99.7 ± 0.3% radiochemical purity, and 192.3 ± 22.5 MBq/nmol molar activity. All process validation batches complied with the product specifications. The acute toxicity of MMP was evaluated at a dose of 3.55 mg/kg body weight, which is 10,000 times the potential maximum clinical dose of [11C]MMP. The acute toxicity of [11C]MMP injection at 150 or 200 times, to administer a postulated dose of 740 MBq of [11C]MMP, was also evaluated after the decay-out of 11C. No acute toxicity of MMP and [11C]MMP injection was found. No mutagenic activity was observed for MMP. The effective dose calculated according to the Medical Internal Radiation Dose (MIRD) method was 5.4 µSv/MBq, and the maximum absorbed dose to the bladder wall was 57.6 µGy/MBq. MMP, a derivative of phenylalkylamine, showed binding to the sigma receptor, but had approximately 1/100 of the affinity of existing sigma receptor imaging agents. The affinity for other brain neuroreceptors was low.
CONCLUSIONS: [11C]MMP shows acceptable pharmacological safety at the dose required for adequate PET imaging. The potential risk associated with [11C]MMP PET imaging is well within the acceptable dose limit.
结果:合成结束时[11C]MMP的衰减校正产率为41.4±6.5%,放射化学纯度为99.7±0.3%,和192.3±22.5MBq/nmol摩尔活性。所有工艺验证批次均符合产品规格。以3.55mg/kg体重的剂量评估MMP的急性毒性,这是[11C]MMP潜在最大临床剂量的10,000倍。[11C]MMP注射液的急性毒性为150或200倍,为了给药740MBq的[11C]MMP,在11C衰减后也进行了评估。未发现MMP和[11C]MMP注射液的急性毒性。未观察到MMP的诱变活性。根据医学内部辐射剂量(MIRD)方法计算的有效剂量为5.4µSv/MBq,膀胱壁的最大吸收剂量为57.6µGy/MBq。MMP,苯烷基胺的衍生物,显示与σ受体结合,但具有现有σ受体显像剂的约1/100的亲和力。对其他脑神经受体的亲和力较低。
结论:[11C]MMP在充分PET成像所需的剂量下显示出可接受的药理学安全性。与[11C]MMPPET成像相关的潜在风险在可接受的剂量范围内。