Metelerkamp Cappenberg Taco, De Schepper Stijn, Vangestel Christel, De Lombaerde Stef, Wyffels Leonie, Van den Wyngaert Tim, Mattis Jeffrey, Gray Brian, Pak Koon, Stroobants Sigrid, Elvas Filipe
Department of Nuclear Medicine, Antwerp University Hospital (UZA), Edegem, Belgium.
Molecular Imaging and Radiology (MIRA), University of Antwerp, Wilrijk, Belgium.
EJNMMI Radiopharm Chem. 2023 Aug 30;8(1):20. doi: 10.1186/s41181-023-00207-1.
Imaging of cell death can provide an early indication of treatment response in cancer. [Tc]Tc-Duramycin is a small-peptide SPECT tracer that recognizes both apoptotic and necrotic cells by binding to phosphatidylethanolamine present in the cell membrane. Preclinically, this tracer has shown to have favorable pharmacokinetics and selective tumor accumulation early after the onset of anticancer therapy. In this first-in-human study, we report the safety, biodistribution and internal radiation dosimetry of [Tc]Tc-Duramycin in healthy human volunteers.
Six healthy volunteers (3 males, 3 females) were injected intravenously with [Tc]Tc-Duramycin (dose: 6 MBq/kg; 473 ± 36 MBq). [Tc]Tc-Duramycin was well tolerated in all subjects, with no serious adverse events reported. Following injection, a 30-min dynamic planar imaging of the abdomen was performed, and whole-body (WB) planar scans were acquired at 1, 2, 3, 6 and 23 h post-injection (PI), with SPECT acquisitions after each WB scan and one low-dose CT after the first SPECT. In vivo Tc activities were determined from semi-quantitative analysis of the images, and time-activity curves were generated. Residence times were calculated from the dynamic and WB planar scans. The mean effective dose was 7.61 ± 0.75 µSv/MBq, with the kidneys receiving the highest absorbed dose (planar analysis: 43.82 ± 4.07 µGy/MBq, SPECT analysis: 19.72 ± 3.42 μGy/MBq), followed by liver and spleen. The median effective dose was 3.61 mSv (range, 2.85-4.14). The tracer cleared slowly from the blood (effective half-life of 2.0 ± 0.4 h) due to high plasma protein binding with < 5% free tracer 3 h PI. Excretion was almost exclusively renal.
[Tc]Tc-Duramycin demonstrated acceptable dosimetry (< 5 mSv) and a favorable safety profile. Due to slow blood clearance, optimal target-to-background ratios are expected 5 h PI. These data support the further assessment of [Tc]Tc-Duramycin for clinical treatment response evaluation.
NCT05177640, Registered April 30, 2021, https://clinicaltrials.gov/study/NCT05177640 .
细胞死亡成像可为癌症治疗反应提供早期指标。[锝（Tc）]Tc-短杆菌肽是一种小肽单光子发射计算机断层扫描（SPECT）示踪剂，通过与细胞膜中存在的磷脂酰乙醇胺结合来识别凋亡细胞和坏死细胞。临床前研究表明，这种示踪剂具有良好的药代动力学特性，并且在抗癌治疗开始后早期有选择性的肿瘤蓄积。在这项首次人体研究中，我们报告了[锝（Tc）]Tc-短杆菌肽在健康人类志愿者中的安全性、生物分布和体内辐射剂量学。
6名健康志愿者（3名男性，3名女性）静脉注射[锝（Tc）]Tc-短杆菌肽（剂量：6 MBq/kg；473±36 MBq）。所有受试者对[锝（Tc）]Tc-短杆菌肽耐受性良好，未报告严重不良事件。注射后，对腹部进行了30分钟的动态平面成像，并在注射后1、2、3、6和23小时采集全身（WB）平面扫描图像，每次WB扫描后进行SPECT采集，第一次SPECT后进行一次低剂量CT扫描。通过对图像的半定量分析确定体内Tc活性，并生成时间-活性曲线。根据动态和WB平面扫描计算滞留时间。平均有效剂量为7.61±0.75 μSv/MBq，肾脏接受的吸收剂量最高（平面分析：43.82±4.07 μGy/MBq，SPECT分析：19.72±3.42 μGy/MBq），其次是肝脏和脾脏。中位有效剂量为3.61 mSv（范围为2.85-4.14）。由于血浆蛋白结合率高，注射后3小时游离示踪剂<5%，示踪剂从血液中清除缓慢（有效半衰期为2.0±0.4小时）。排泄几乎完全通过肾脏。
[锝（Tc）]Tc-短杆菌肽显示出可接受的剂量学（<5 mSv）和良好的安全性。由于血液清除缓慢，预计注射后5小时靶本底比最佳。这些数据支持对[锝（Tc）]Tc-短杆菌肽进行进一步评估以用于临床治疗反应评估。
NCT05177640，2021年4月30日注册，https://clinicaltrials.gov/study/NCT05177640 。
