[(153)Sm]Samarium-labeled FAPI-46 radioligand therapy in a patient with lung metastases of a sarcoma.
[(153)Sm]Samarium-labeled FAPI-46 radioligand therapy in a patient with lung metastases of a sarcoma.
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DOI：
10.1007/s00259-021-05273-8
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发表时间：
2021-08
影响因子：
9.1
通讯作者：
Haberkorn U
中科院分区：
文献类型：
--
作者：
Kratochwil C;Giesel FL;Rathke H;Fink R;Dendl K;Debus J;Mier W;Jäger D;Lindner T;Haberkorn U
成纤维细胞激活蛋白由多种肿瘤实体基质中的癌症相关成纤维细胞 (CAF) 过度表达，并提供抗免疫原作用 [1]。它可以用放射性标记的小分子抑制剂 (FAPI) 来靶向[2]。该图像显示一名患有肺转移性纤维梭形细胞软组织肉瘤进展的患者。位于膀胱和直肠之间的原发肿瘤以及早期的寡灶转移瘤以前曾通过切除和外照射放射治疗进行治疗。在全身阶段，基于突变的疫苗接种[3]、环磷酰胺和帕唑帕尼已被使用，但患者被认为不适合接受蒽环类标准化疗。一次跨学科肿瘤会议认为实验性 FAPI-RLT 对于这种治疗难治性患者来说是一个有前途的选择，可以作为成功免疫治疗的“开罐器”。 FAPI-PET/CT 显示靶点阳性肿瘤表型 (a)。由于喹啉基FAPI-46的生物肿瘤半衰期相对较短[1]，因此它被标记为较短的物理半衰期（46.3 h）153Sm。治疗期间的发射扫描表明，肿瘤在注射后 44 小时内具有靶向性，并能从正常器官中快速清除 (b)。累积 20 GBq 153Sm-和 8GBq Y-90-FAPI-46（153Sm 没有足够高的比活性）的三个周期具有良好的耐受性，并在 8 个月内实现疾病稳定（c）。接下来的治疗线是派姆单抗（通过溶瘤细小病毒 [4] 进行实验增强）和白蛋白结合型紫杉醇。在这两种疗法下，患者仅 3 个月后病情出现进展。在这种特殊情况下，90Y/153Sm-FAPI-46 的临床活性的一种解释可能是 CAF 和肉瘤肿瘤细胞中的 FAP 表达 [5]，不幸的是，在其他肿瘤实体中并非如此。当然，一个病例并不能证明总体疗效，但显然这张图片鼓励进一步研究 FAPI-RLT 对抗软组织肉瘤。然而，由于与 153Sm 相关的技术问题，例如，关于 154Eu 的比活度和污染，应评估其他短物理半衰期同位素作为替代选择。
Fibroblast activation protein is overexpressed by cancerassociated fibroblasts (CAFs) in the stroma of several tumor entities and provides anti-immunogenic effects [1]. It can be targeted with radiolabeled small-molecule inhibitors (FAPIs)[2]. This image demonstrates a patient with progression of lung metastatic, fibrous spindle cell soft tissue sarcoma. Primary tumor located between bladder and rectum as well as early generations of oligo-focal metastases had previously been treated by resection and external-beam radiotherapy. In systemic stage, mutanom-based vaccination [3], cyclophosphamide, and pazopanib had already been used but the patient was considered inappropriate for standard chemotherapy with anthracyclines. An interdisciplinary tumor conference considered experimental FAPI-RLT a promising option for this therapy-refractory patient to serve as a “can opener” for succeeding immunotherapy. FAPI-PET/CT demonstrated target positive tumor phenotype (a). Due to the relatively short biological tumor halflife of quinoline-based FAPI-46 [1], it was labeled with short physical half-life (46.3 h) 153Sm. Emission scans during therapy demonstrate tumor targeting up to 44 h pi and rapid clearance from normal organs (b). Three cycles with cumulative 20 GBq 153Sm-and 8GBq Y-90-FAPI-46 (153Sm was not available with sufficiently high specific activity) were well tolerated and achieved stable disease for 8 months (c). Next treatment lines were pembrolizumab, experimentally enhanced with oncolytic parvovirus [4], and nab-paclitaxel. Under both therapies, the patient progressed after only 3 months.One explanation for the clinical activity of 90Y/153Sm-FAPI-46 in this particular case might be FAP expression in both CAFs and sarcoma tumor cells [5], which is unfortunately not the case in other tumor entities. Of course, one case is no proof of general efficacy but obviously this image encourages further studies of FAPI-RLT against soft tissue sarcoma. However, due to technical issues related to 153Sm, eg, regarding specific activity and contamination with 154Eu, additional short physical half-life isotopes should be evaluated as alternative options.
影响因子：
6.4
作者：
Dohi O;Ohtani H;Hatori M;Sato E;Hosaka M;Nagura H;Itoi E;Kokubun S
通讯作者：
Kokubun S
影响因子：
11.5
作者：
Tuereci, Oezlem;Vormehr, Mathias;Sahin, Ugur
通讯作者：
Sahin, Ugur
DOI：
10.2967/jnumed.118.215913
发表时间：
2019-03
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Giesel FL;Kratochwil C;Lindner T;Marschalek MM;Loktev A;Lehnert W;Debus J;Jäger D;Flechsig P;Altmann A;Mier W;Haberkorn U
通讯作者：
Haberkorn U