Department of Nuclear Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.
European Neuroendocrine Tumor Society (ENETS) Center of Excellence, University Hospital Wuerzburg, Wuerzburg, Germany.
Mol Imaging Biol. 2019 Aug;21(4):790-798. doi: 10.1007/s11307-018-1293-9.
As has been previously reported, the somatostatin receptor (SSTR) imaging agent [Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotate ([Ga]DOTATATE) demonstrates lower uptake in normal organs in patients with a high neuroendocrine tumor (NET) burden. Given the higher SSTR affinity of [Ga] DOTATATE, we aimed to quantitatively investigate the biodistribution of [Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ([Ga]DOTATOC) to determine a potential correlation between uptake in normal organs and NET burden.
Of the 44 included patients, 36/44 (82 %) patients demonstrated suspicious radiotracer uptake on [Ga] DOTATOC positron emission tomography (PET)/X-ray computed tomography (CT). Volumes of interest (VOIs) were defined for tumor lesions and normal organs (spleen, liver, kidneys, adrenals). Mean body weight corrected standardized uptake value (SUV) for normal organs was assessed and was used to calculate the corresponding mean specific activity uptake (Upt: fraction of injected activity per kg of tissue). For the entire tumor burden, SUV, maximum standardized uptake value (SUV), and the total mass (TBM) was calculated and the decay corrected tumor fractional uptake (TBU) was assessed. A Spearman's rank correlation coefficient was used to determine the correlations between normal organ uptake and tumor burden.
The median SUV was 18.7 for the spleen (kidneys, 9.2; adrenals, 6.8; liver, 5.6). For tumor burden, the median values were SUV 6.9, SUV 35.5, TBM 42.6 g, and TBU 1.2 %. With increasing volume of distribution, represented by lean body mass and body surface area (BSA), Upt decreased in kidneys, liver, and adrenal glands and SUV increased in the spleen. Correlation improved only for both kidneys and adrenals when the influence of the tumor uptake on the activity available for organ uptake was taken into account by the factor 1/(1-TBU). TBU was neither predictive for SUV nor for Upt in any of the organs. The distribution of organ Upt vs. BSA/(1-TBU) were not different for patients with minor TBU (<3 %) vs. higher TBU (>7 %), indicating that the correlations observed in the present study are explainable by the body size effect. High tumor mass and uptake mitigated against G1 NET.
There is no significant impact on normal organ biodistribution with increasing tumor burden on [Ga] DOTATOC PET/CT. Potential implications include increased normal organ dose with [Lu-DOTA]-D-Phe-Tyr-Octreotide and decreased absolute lesion detection with [Ga] DOTATOC in high NET burden.
正如之前所报道的，生长抑素受体（SSTR）成像剂 [Ga]-标记的 1,4,7,10-四氮杂环十二烷-N,N',N″,N‴-四乙酸-d-Phe(1)-Tyr(3)-奥曲肽 ([Ga]DOTATATE) 在高神经内分泌肿瘤（NET）负荷的患者中，正常器官的摄取较低。鉴于 [Ga] DOTATATE 具有更高的 SSTR 亲和力，我们旨在定量研究 [Ga]-标记的 1,4,7,10-四氮杂环十二烷-N,N',N″,N‴-四乙酸-d-Phe(1)-Tyr(3)-奥曲肽 ([Ga]DOTATOC) 的生物分布，以确定正常器官摄取与 NET 负荷之间的潜在相关性。
在纳入的 44 名患者中，36/44（82%）名患者的 [Ga] DOTATOC 正电子发射断层扫描（PET）/X 射线计算机断层扫描（CT）显示可疑放射性示踪剂摄取。为肿瘤病变和正常器官（脾脏、肝脏、肾脏、肾上腺）定义了感兴趣区（VOI）。评估正常器官的体重校正标准化摄取值（SUV），并用于计算相应的平均特异性摄取（Upt：组织每公斤的放射性活度分数）。对于整个肿瘤负担，计算 SUV、最大标准化摄取值（SUVmax）和总质量（TBM），并评估衰减校正的肿瘤分数摄取（TBU）。使用 Spearman 秩相关系数确定正常器官摄取与肿瘤负担之间的相关性。
脾脏的中位数 SUV 为 18.7（肾脏，9.2；肾上腺，6.8；肝脏，5.6）。对于肿瘤负担，中位数值为 SUV 6.9、SUV 35.5、TBM 42.6 g 和 TBU 1.2%。随着代表瘦体重和体表面积（BSA）的分布容积增加，肾脏、肝脏和肾上腺中的 Upt 降低，脾脏中的 SUV 增加。当考虑到肿瘤摄取对器官摄取的可用活性的影响因子 1/（1-TBU）时，仅当考虑到肿瘤摄取对器官摄取的可用活性的影响时，相关性才会改善。TBU 既不能预测任何器官的 SUV 也不能预测 Upt。对于 TBU 小于 3%的患者与 TBU 大于 7%的患者，器官 Upt 与 BSA/（1-TBU）的分布没有差异，这表明本研究中观察到的相关性可以用体型效应来解释。高肿瘤负荷和摄取减轻了 G1 NET。
[Ga] DOTATOC PET/CT 上肿瘤负担的增加对正常器官的生物分布没有显著影响。潜在影响包括 [Lu-DOTA]-D-Phe-Tyr-Octreotide 时正常器官剂量增加和 [Ga] DOTATOC 时高 NET 负荷时绝对病变检测减少。
