PDF(Pubmed)
Abstract：
[11C]Carfentanil ([11C]CFN) is the only selective carbon-11 labeled radiotracer currently available for positron emission tomography (PET) imaging of mu opioid receptors (MORs). Though used extensively in clinical research, [11C]CFN has not been thoroughly characterized as a tool for preclinical PET imaging. As we were occasionally observing severe vital sign instability in rat [11C]CFN studies, we set out to investigate physiological effects of CFN mass and to explore its influence on MOR quantification. In anesthetized rats (n = 15), significant dose-dependent PCO2 increases and heart rate decreases were observed at a conventional tracer dose range (IV, > 100 ng/kg). Next, we conducted baseline and retest [11C]CFN PET scans over a wide range of molar activities. Baseline [11C]CFN PET studies (n = 27) found that nondisplaceable binding potential (BPND) in the thalamus was positively correlated to CFN injected mass, demonstrating increase of MOR availability at higher injected CFN mass. Consistently, when CFN injected mass was constrained < 40 ng/kg (~ 10% MOR occupancy in rats), baseline MOR availability was significantly decreased. For test-retest variability (TRTV), better reproducibility was achieved by controlling CFN injected mass to limit the difference between scans. Taken together, we report significant cardiorespiratory depression and a paradoxical influence on baseline MOR availability at conventional tracer doses in rats. Our findings might reflect changes in cerebral blood flow, changes in receptor affinity, or receptor internalization, and merits further mechanistic investigation. In conclusion, rat [11C]CFN PET requires stringent quality assurance of radiotracer synthesis and mass injected to avoid pharmacological effects and limit potential influences on MOR quantification and reproducibility.
摘要：
[11C]卡芬太尼（[11C]CFN）是目前可用于μ阿片受体（MORs）正电子发射断层扫描（PET）成像的唯一选择性碳11标记的放射性示踪剂。尽管在临床研究中广泛使用，[11C]CFN尚未被彻底表征为临床前PET成像的工具。由于我们偶尔在大鼠[11C]CFN研究中观察到严重的生命体征不稳定，我们着手研究CFN质量的生理效应，并探讨其对MOR定量的影响。在麻醉大鼠中（n=15），在常规示踪剂剂量范围（IV，>100ng/kg)。接下来,我们在广泛的摩尔活动范围内进行了基线和重新测试[11C]CFNPET扫描。基线[11C]CFNPET研究（n=27）发现丘脑中的不可置换结合电位（BPND）与CFN注射质量呈正相关，证明在较高的注入CFN质量下MOR可用性增加。始终如一，当CFN注射质量限制<40ng/kg(大鼠MOR占有率~10%)时，基线MOR可用性显著降低。对于测试-重测变异性(TRTV)，通过控制CFN注射质量以限制扫描之间的差异，可以实现更好的再现性。一起来看,我们报道了大鼠常规示踪剂剂量下显著的心肺抑制和对基线MOR可用性的矛盾影响.我们的发现可能反映了脑血流量的变化，受体亲和力的变化，或受体内化，并值得进一步进行机械调查。总之,大鼠[11C]CFNPET需要严格的放射性示踪剂合成和注射质量的质量保证，以避免药理作用并限制对MOR定量和可重复性的潜在影响。
