Pabst Kim M, Weber Manuel M, Laschinsky Christina, Sandach Patrick, Bartel Timo, Küper Alina T, Kessler Lukas, Trajkovic-Arsic Marija, Eckstein Markus, Gilman Elena, Nader Michael, Barbato Francesco, Podleska Lars E, Hadaschik Boris A, Hamacher Rainer, Kersting David, von Ostau Nicola, von Tresckow Bastian, Kaelberlah Hans-Peter, Kesch Claudia, Kuemmel Sherko, Reinacher-Schick Anke, Schuler Martin, Siveke Jens T, Grünwald Viktor, Herrmann Ken, Fendler Wolfgang P
Department of Nuclear Medicine, West German Cancer Center, German Cancer Consortium and National Center for Tumor Diseases site, University Hospital Essen, Essen, Germany.
Medizin Center Bonn, Bonn, Germany.
Lancet Oncol. 2025 Sep;26(9):1204-1214. doi: 10.1016/S1470-2045(25)00299-2. Epub 2025 Aug 4.
The fibroblast activation protein α (FAP)-directed radiotracer [Ga]Ga-FAPI-46 for PET-CT has shown promising diagnostic accuracy in cancer staging in retrospective studies. We aim to investigate the positive predictive value (PPV) of [Ga]Ga-FAPI-46 PET for detecting FAP-expressing tumours and the potential association between PET radiotracer uptake intensity and immunohistochemical FAP expression.
This single-centre, single-arm, interventional, phase 2 trial was conducted at the University Hospital Essen, Essen, Germany. Adults aged 18 years or older undergoing initial staging or restaging were eligible if they had at least one measurable tumour lesion (>1 cm) and a confirmed or suspected diagnosis of breast cancer, colorectal cancer, endometrial cancer, oesophageal cancer, head and neck cancer, ovarian cancer, pancreatic ductal adenocarcinoma (PDAC), prostate cancer, thyroid cancer, glioma, hepatocellular carcinoma, lymphoma, multiple myeloma, non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), sarcoma, seminoma, cancer of unknown primary origin, or other tumour types; had a planned or recent surgery or biopsy within 8 weeks before or after enrolment; and an ECOG performance status of 2 or less. Key exclusion criteria were previous external beam radiotherapy to the target lesion and receiving systemic cancer therapy within 1 month before enrolment. PET-CT images were acquired at a median of 11 min (IQR 10-14) after an intravenous injection of a median of 145 Megabecquerel (MBq; 124-154) of [Ga]Ga-FAPI-46 and analysed by three independent, masked readers. The study concluded on day 30 of follow-up if histopathological confirmation and archived tumour tissue were already available, or on the day of biopsy or surgery within 8 weeks of receiving [Ga]Ga-FAPI-46 PET-CT. Immunohistochemical FAP expression (score 0-3) was evaluated by an independent masked pathologist. The primary endpoint was the PPV of [Ga]Ga-FAPI-46 PET for detecting immunohistochemical FAP-positive tumours (histopathologically confirmed) on a per-patient and per-region basis, with a predefined threshold of PPV of at least 75%, analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT05160051, and is complete.
Between Dec 1, 2021, and Feb 6, 2024, 158 eligible participants were enrolled and three were excluded. 98 (63%) of 155 participants who received [Ga]Ga-FAPI-46 PET-CT were male and 57 (37%) were female. One (1%) participant was African, two (1%) were Asian, and 152 (98%) were White. The median age of participants was 62 years (IQR 55-70). The median follow-up was 29 days (29-30). The patient-based PPV of [Ga]Ga-FAPI-46 PET for detecting FAP-positive tumours based on immunohistochemical FAP staining was 90% (95% CI 84-95) and region-based PPV was 92% (85-96) in 127 (88%) of 144 participants with histopathological validation. Five (6%) of 90 adverse events were classified as possibly related to [Ga]Ga-FAPI-46. Seven (8%) adverse events were serious, none related to [Ga]Ga-FAPI-46. One participant died due to disease progression.
These results confirm the safety and potential of [Ga]Ga-FAPI-46 PET as an imaging biomarker for the detection of FAP-expressing tumours. Further studies are warranted to refine the specificity and define the role of [Ga]Ga-FAPI-46 PET in clinical practice.
SOFIE Biosciences.
在回顾性研究中，用于正电子发射断层扫描-计算机断层扫描（PET-CT）的成纤维细胞活化蛋白α（FAP）导向放射性示踪剂[镓]Ga-FAPI-46在癌症分期方面显示出有前景的诊断准确性。我们旨在研究[镓]Ga-FAPI-46 PET检测FAP表达肿瘤的阳性预测值（PPV）以及PET放射性示踪剂摄取强度与免疫组化FAP表达之间的潜在关联。
这项单中心、单臂、干预性2期试验在德国埃森大学医院进行。年龄在18岁及以上、正在接受初始分期或再分期的成年人符合条件，前提是他们至少有一个可测量的肿瘤病灶（>1 cm），且确诊或疑似患有乳腺癌、结直肠癌、子宫内膜癌、食管癌、头颈癌、卵巢癌、胰腺导管腺癌（PDAC）、前列腺癌、甲状腺癌、神经胶质瘤、肝细胞癌、淋巴瘤、多发性骨髓瘤、非小细胞肺癌（NSCLC）、肾细胞癌（RCC）、肉瘤、精原细胞瘤、原发灶不明癌或其他肿瘤类型；在入组前或入组后8周内计划进行或近期进行过手术或活检；且东部肿瘤协作组（ECOG）体能状态为2或更低。主要排除标准是之前对靶病灶进行过外照射放疗以及在入组前1个月内接受过全身性癌症治疗。在静脉注射中位剂量为145兆贝可（MBq；124 - 154）的[镓]Ga-FAPI-46后，中位11分钟（四分位间距10 - 14）采集PET-CT图像，并由三名独立的、不知情的阅片者进行分析。如果组织病理学确认和存档的肿瘤组织已经可用，则在随访第30天结束研究，或者在接受[镓]Ga-FAPI-46 PET-CT后8周内的活检或手术当天结束研究。由一名独立的不知情病理学家评估免疫组化FAP表达（评分0 - 3）。主要终点是[镓]Ga-FAPI-46 PET在每位患者和每个区域检测免疫组化FAP阳性肿瘤（经组织病理学确认）的PPV，PPV的预定义阈值至少为75%，在意向性治疗人群中进行分析。本研究已在ClinicalTrials.gov注册，注册号为NCT05160051，且已完成。
在2021年12月1日至2024年2月6日期间，158名符合条件的参与者入组，3名被排除。155名接受[镓]Ga-FAPI-46 PET-CT的参与者中，98名（63%）为男性，57名（37%）为女性。1名（1%）参与者为非洲裔，2名（1%）为亚洲裔，152名（98%）为白人。参与者的中位年龄为62岁（四分位间距55 - 70）。中位随访时间为29天（29 - 30）。在144名有组织病理学验证的参与者中的127名（88%）中，基于免疫组化FAP染色，[镓]Ga-FAPI-46 PET检测FAP阳性肿瘤的基于患者的PPV为90%（95%置信区间84 - 95），基于区域的PPV为92%（85 - 96）。90例不良事件中有5例（6%）被归类为可能与[镓]Ga-FAPI-46相关。7例（8%）不良事件为严重不良事件，均与[镓]Ga-FAPI-46无关。1名参与者因疾病进展死亡。
这些结果证实了[镓]Ga-FAPI-46 PET作为检测FAP表达肿瘤的成像生物标志物的安全性和潜力。有必要进行进一步研究以提高其特异性，并确定[镓]Ga-FAPI-46 PET在临床实践中的作用。
SOFIE生物科学公司。
