First-in-Human Trial of Epichaperome-Targeted PET in Patients with Cancer.
First-in-Human Trial of Epichaperome-Targeted PET in Patients with Cancer.
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DOI：
10.1158/1078-0432.ccr-19-3704
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发表时间：
2020-10-01
期刊：
影响因子：
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通讯作者：
Larson SM
中科院分区：
文献类型：
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作者：
Dunphy MPS;Pressl C;Pillarsetty N;Grkovski M;Modi S;Jhaveri K;Norton L;Beattie BJ;Zanzonico PB;Zatorska D;Taldone T;Ochiana SO;Uddin MM;Burnazi EM;Lyashchenko SK;Hudis CA;Bromberg J;Schöder HM;Fox JJ;Zhang H;Chiosis G;Lewis JS;Larson SM
124 I-PU-H71是一种研究中的一流放射性药物，专门用于肿瘤epichaperome形成的成像。细胞内epichaperome在细胞应激下形成，并且是临床验证的肿瘤治疗靶点。我们进行了一项首次在人体内进行的微剂量124 I-PU-H71正电子发射断层扫描（PET）研究，以研究体内生物分布，药代动力学，代谢和安全性;以及epichaperome靶向肿瘤成像的可行性。患有癌症的成年患者（n=30）接受124 I-PU-H71示踪剂（201±12 MBq，<25 μg）IV推注，随后进行PET/CT扫描和血液放射性测定。124 I-PU-H71 PET检测不同癌症类型的肿瘤（乳腺癌、淋巴瘤、神经母细胞瘤、泌尿生殖系统肿瘤、妇科肿瘤、肉瘤和胰腺肿瘤）。~（124）I-PU-H71在肿瘤中滞留数天，而从骨、健康软组织和血液中迅速清除。辐射剂量测定是有利的，患者没有受到不良影响。我们的首次人体试验结果证明了使用124 I-PU-H71 PET进行肿瘤epichaperomes非侵入性体内检测的安全性和可行性，支持PU-H71和其他epichaperome-targeted疗法的临床开发。
124I-PU-H71 is an investigational first-in-class radiologic agent specific for imaging tumor epichaperome formations. The intracellular epichaperome forms under cellular stress and is a clinically validated oncotherapeutic target. We conducted a first-in-human study of microdose 124I-PU-H71 for positron emission tomography (PET) to study in vivo biodistribution, pharmacokinetics, metabolism, and safety; and the feasibility of epichaperome-targeted tumor imaging. Adult patients with cancer (n=30) received 124I-PU-H71 tracer (201±12 MBq, <25 μg) IV bolus followed by PET/CT scans and blood radioassays. 124I-PU-H71 PET detected tumors of different cancer types (breast, lymphoma, neuroblastoma, genitourinary, gynecologic, sarcoma, and pancreas). 124I-PU-H71 was retained by tumors for several days while it cleared rapidly from bones, healthy soft tissues, and blood. Radiation dosimetry is favorable and patients suffered no adverse effects. Our first-in-human results demonstrate the safety and feasibility of non-invasive in vivo detection of tumor epichaperomes using 124I-PU-H71 PET, supporting clinical development of PU-H71 and other epichaperome-targeted therapeutics.