First-in-human study of a novel cell death tracer [99mTc]Tc-Duramycin: safety, biodistribution and radiation dosimetry in healthy volunteers

Background Imaging of cell death can provide an early indication of treatment response in cancer. [ 99m 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 ha...

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Veröffentlicht in:EJNMMI Radiopharmacy and Chemistry 2023-08, Vol.8 (1), p.20-20, Article 20
Hauptverfasser: 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
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Sprache:eng
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Zusammenfassung:Background Imaging of cell death can provide an early indication of treatment response in cancer. [ 99m 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 [ 99m Tc]Tc-Duramycin in healthy human volunteers. Results Six healthy volunteers (3 males, 3 females) were injected intravenously with [ 99m Tc]Tc-Duramycin (dose: 6 MBq/kg; 473 ± 36 MBq). [ 99m 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 99m 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 
ISSN:2365-421X
2365-421X
DOI:10.1186/s41181-023-00207-1