背景:放射性标记的成纤维细胞激活蛋白(FAP)配体,用于PET/CT成像的新型示踪剂,在各种肿瘤学中表现出非常有希望的结果,以及在一些良性的,具有长期潜力的疾病在某些癌症类型中取代当前的泛癌症剂[18F]FDG。胰腺导管癌(PDAC)属于上皮性恶性肿瘤,具有强烈的所谓“促纤维化反应”,导致与癌症相关的成纤维细胞表现出成纤维细胞活化蛋白(FAP)的明显过表达的突出肿瘤基质。在PDAC中使用68Ga标记的FAP配体的首次临床经验表明对[18F]FDG具有优异的敏感性。然而,18F标记的FAP衍生物的数据有限,即[18F]FAPI-74,但前瞻性单中心和多中心试验已经在进行中。在这个概念验证研究中,我们试图评估生物分布,肿瘤摄取,与[18F]FDGPET/CT扫描分期相比,使用[18F]FAPI-74PET/CT对PDAC患者的病变检测能力。
方法:本研究包括7例患者(中位年龄69岁),这些患者同时接受了[18F]FDGPET/CT增强扫描和[18F]FAPI-74PET低剂量CT扫描以进行原发性分期(n=3)和新辅助治疗后(n=1)或姑息治疗后(n=3)的治疗反应控制。PET扫描之间的平均间隔为11±4天(范围1-15天)。在64±4.1min(范围61-91min)和66.4±6.3min(范围60-76min)时采集[18F]FDG和[18F]FAPI-74PET/CT扫描,分别,给药200±94MBq(范围79-318MBq)和235±88MBq(范围90-321MBq)后,分别。示踪剂摄取的定量用SUVmax和SUVmean测定。此外,肿瘤背景比(TBR)是通过将肿瘤病变的SUVmax除以脂肪组织的SUVmax得出的,骨骼肌,和血池。
结果:总体而言,在7例患者中检测到32个病灶,包括原发性(n=7),肺(n=7),骨(n=3),淋巴结(n=13),和腹膜转移(n=2)。与[18F]FDG相比,[18F]FAPI-74检测到的病变多22%,TBR和视觉病变描绘更好。在一名患者中,[18F]FAPI-74可以明确检测到原发性病变,但[18F]FDG成像漏诊。总之,大多数病变显示[18F]FAPI-74的摄取显着升高,同时在背景中摄取较低,提供非常高的视觉对比度。
结论:据我们所知,这是第一个,prospective,在PDAC中比较[18F]FAPI-74和[18F]FDG成像的个体内部调查,结果令人鼓舞。这些枢轴结果支持更大的,多中心,前瞻性研究,以确定[18F]FAPI-74在检测和分期PDAC中的价值,并与当前的护理成像标准进行比较。
BACKGROUND: Radiolabeled fibroblast activation protein (FAP) ligands, a novel class of tracers for PET/CT imaging, have demonstrated very promising results in various oncological, as well as in some benign, diseases with long-term potential to supplant the current pan-cancer agent [18F]FDG in some cancer types. Pancreatic ductal carcinoma (PDAC) belongs to the group of epithelial malignancies with a strong so-called \"desmoplastic reaction\", leading to a prominent tumor stroma with cancer-associated fibroblasts that exhibit a marked overexpression of fibroblast activation protein (FAP). The first clinical experiences in PDAC with 68Ga-labeled FAP ligands suggested superior sensitivity to [18F]FDG. However, there is limited data with 18F-labeled FAP derivatives, i.e. [18F]FAPI-74, yet prospective single- and multicenter trials are already ongoing. In this proof-of-concept
study, we sought to evaluate the biodistribution, tumor uptake, and lesion detectability in patients with PDAC using [18F]FAPI-74 PET/CT as compared to [18F]FDG PET/CT scans for staging.
METHODS: This
study includes 7 patients (median age 69) who underwent both [18F]FDG PET/CT with contrast-enhancement and [18F]FAPI-74 PET with low-dose CT for primary staging (n = 3) and therapy response control after neoadjuvant (n = 1) or re-staging after palliative therapy (n = 3). The mean interval between PET scans was 11 ± 4 days (range 1-15 days). The [18F]FDG and [18F]FAPI-74 PET/CT scans were acquired at 64 ± 4.1 min (range 61-91 min) and 66.4 ± 6.3 min (range 60-76 min), respectively, after administration of 200 ± 94 MBq (range 79-318 MBq) and 235 ± 88 MBq (range 90-321 MBq), respectively. Quantification of tracer uptake was determined with SUVmax and SUVmean. Furthermore, the tumor-to-background ratio (TBR) was derived by dividing the SUVmax of tumor lesions by the SUVmax of adipose tissue, skeletal muscle, and blood pool.
RESULTS: Overall, 32 lesions were detected in 7 patients including primary (n = 7), lung (n = 7), bone (n = 3), lymph node (n = 13), and peritoneal metastases (n = 2). [18F]FAPI-74 detected 22% more lesions compared with [18F]FDG with a better TBR and visual lesion delineation. In one patient the primary lesion could be detected unequivocally with [18F]FAPI-74 but was missed by [18F]FDG imaging. Altogether, most of the lesions demonstrated markedly elevated uptake of [18F]FAPI-74 with a simultaneous lower uptake in the background, providing a very high visual contrast.
CONCLUSIONS: To the best of our knowledge, this is the first, prospective, intra-individual investigation comparing [18F]FAPI-74 with [18F]FDG imaging in PDAC with encouraging results. These pivotalresults supporta larger, multicentric, prospective
study to determine the value of [18F]FAPI-74 in detecting and staging PDAC in comparison with current standard of care imaging.