Blanchet Elise M, Taieb David, Millo Corina, Martucci Victoria, Chen Clara C, Merino Maria, Herscovitch Peter, Pacak Karel
Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland.
La Timone University Hospital, European Center for Research in Medical Imaging, Aix-Marseille University, Marseille, France.
J Nucl Med. 2015 Dec;56(12):1849-54. doi: 10.2967/jnumed.115.159061. Epub 2015 Sep 10.
(18)F-FDG PET/CT has been proven to be a highly sensitive method for pheochromocytomas/paragangliomas (PHEOs/PGLs) associated with succinate dehydrogenase (SDH) mutations. This finding has been attributed to altered tumor cell metabolism resulting from these mutations and does not provide additional prognostic information to genotype. Therefore, identification of new biomarkers for aggressiveness is needed. A high Ki-67 index was proposed to be an additional prognostic factor. This pilot study aimed to evaluate 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET/CT, a PET proliferation tracer, as a potential imaging agent in a series of 12 PHEO/PGL patients with different genetic backgrounds, to compare (18)F-FLT uptake with (18)F-FDG PET/CT, and to evaluate classic factors of aggressiveness.
Twelve patients (7 metastatic and 5 nonmetastatic) were prospectively evaluated with (18)F-FDG and (18)F-FLT and followed for at least 2 y after the initial imaging work-up. Uptake was assessed at a lesion level, visually and quantitatively by maximum standardized uptake values (SUVmax) for both tracers. (18)F-FLT uptake was compared with risk factors known to be linked with a poor prognosis in PGLs (SDHB-mutated status, lesion size, dopaminergic phenotype) and with (18)F-FDG uptake.
In 12 patients, 77 lesions were assessed. All lesions had low (18)F-FLT uptake (median SUVmax, 2.25; range, 0.7-4.5). There was no apparent superiority of (18)F-FLT uptake in progressive lesions, and most of the lesions showed a mismatch, with high (18)F-FDG uptake (median SUVmax, 10.8; range, 1.1-79.0) contrasting with low (18)F-FLT uptake.
This study suggests that PHEOs/PGLs-even those that progress-do not exhibit intense (18)F-FLT uptake. It provides the first in vivo demonstration that proliferation may not be a major determinant of (18)F-FDG uptake in these tumors. These findings provide new insight into the biologic behavior of PGL and suggest that antiproliferative agents may be suboptimal for treatment of these tumors.
已证实（18）F - FDG PET/CT是检测与琥珀酸脱氢酶（SDH）突变相关的嗜铬细胞瘤/副神经节瘤（PHEOs/PGLs）的高灵敏度方法。这一发现归因于这些突变导致的肿瘤细胞代谢改变，且未提供超出基因型的额外预后信息。因此，需要鉴定新的侵袭性生物标志物。有人提出高Ki - 67指数是一个额外的预后因素。这项初步研究旨在评估3'-脱氧-3'-（18）F - 氟胸苷（（18）F - FLT）PET/CT，一种PET增殖示踪剂，作为一系列12例具有不同遗传背景的PHEO/PGL患者的潜在成像剂，比较（18）F - FLT摄取与（18）F - FDG PET/CT，并评估侵袭性的经典因素。
对12例患者（7例转移性和5例非转移性）进行前瞻性（18）F - FDG和（18）F - FLT评估，并在初始成像检查后随访至少2年。在病灶水平通过两种示踪剂的最大标准化摄取值（SUVmax）进行视觉和定量评估摄取情况。将（18）F - FLT摄取与已知与PGL预后不良相关的危险因素（SDHB突变状态、病灶大小、多巴胺能表型）以及（18）F - FDG摄取进行比较。
对12例患者的77个病灶进行了评估。所有病灶的（18）F - FLT摄取均较低（SUVmax中位数为2.25；范围为0.7 - 4.5）。在进展性病灶中，（18）F - FLT摄取没有明显优势，且大多数病灶表现出不匹配，（18）F - FDG摄取高（SUVmax中位数为10.8；范围为1.1 - 79.0），而（18）F - FLT摄取低。
本研究表明，PHEOs/PGLs——即使是进展性的——也不会表现出强烈的（18）F - FLT摄取。它首次在体内证明增殖可能不是这些肿瘤中（18）F - FDG摄取的主要决定因素。这些发现为PGL的生物学行为提供了新的见解，并表明抗增殖药物可能不是治疗这些肿瘤的最佳选择。
