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

• Published in: EJNMMI radiopharmacy and chemistry Vol. 8; no. 1; p. 20
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 30.08.2023; Springer Nature B.V; SpringerOpen
• Subjects: 99mTc-duramycin SPECT; Apoptosis; Binding; Biodistribution; Blood; Cell death; Cell death imaging; Cell membranes; Computed tomography; Dosimeters; Dosimetry; Half-life; Imaging; In vivo methods and tests; Injection; Internal dosimetry; Medical imaging; Medicine; Medicine & Public Health; Molecular Medicine; Nuclear Chemistry; Nuclear Medicine; Pharmacokinetics; Pharmacotherapy; Phosphatidylethanolamine; Radiation; Radiation dosimetry; Radioactive half-life; Radiology; Renal function; Research Article; Safety; Single photon emission computed tomography; Technetium isotopes; Tc-duramycin SPECT; Cell death imaging; Biodistribution; Internal dosimetry; Apoptosis
• ISSN: 2365-421X; 2365-421X
• DOI: 10.1186/s41181-023-00207-1

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 < 5% free tracer 3 h PI. Excretion was almost exclusively renal. Conclusion [ 99m 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 [ 99m Tc]Tc-Duramycin for clinical treatment response evaluation. Trial registration : NCT05177640, Registered April 30, 2021, https://clinicaltrials.gov/study/NCT05177640 .