A first-in-human study of [ 68 Ga]Ga-CDI: a positron emitting radiopharmaceutical for imaging tumour cell death.

Autor: Ho Shon I; Department of Nuclear Medicine and PET, Prince of Wales Hospital, Sydney, Australia. i.hoshon@unsw.edu.au.; The Centenary Institute, University of Sydney, Sydney, Australia. i.hoshon@unsw.edu.au.; Prince of Wales Clinical School, University of New South Wales, Sydney, Australia. i.hoshon@unsw.edu.au., Hennessy T; Department of Nuclear Medicine and PET, Prince of Wales Hospital, Sydney, Australia., Guille J; Department of Nuclear Medicine and PET, Prince of Wales Hospital, Sydney, Australia., Gotsbacher MP; School of Medical Sciences, University of Sydney, Sydney, Australia., Lay AJ; The Centenary Institute, University of Sydney, Sydney, Australia., McBride B; Department of Nuclear Medicine and PET, Prince of Wales Hospital, Sydney, Australia., Codd R; School of Medical Sciences, University of Sydney, Sydney, Australia., Hogg PJ; The Centenary Institute, University of Sydney, Sydney, Australia.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2022 Oct; Vol. 49 (12), pp. 4037-4047. Date of Electronic Publication: 2022 Jul 02.
DOI: 10.1007/s00259-022-05880-z
Abstrakt: Purpose: This study assesses human biodistribution, radiation dosimetry, safety and tumour uptake of cell death indicator labelled with 68 Ga ([ 68 Ga]Ga-CDI), a novel radiopharmaceutical that can image multiple forms of cell death.
Methods: Five participants with at least one extracranial site of solid malignancy > 2 cm and no active cancer treatment in the 8 weeks prior to the study were enrolled. Participants were administered 205 ± 4.1 MBq (range, 200-211 MBq) of [ 68 Ga]Ga-CDI and 8 serial PET scans acquired: the first commencing immediately and the last 3 h later. Participants were monitored for clinical, laboratory and electrocardiographic side effects and adverse events. Urine and blood radioactivity was measured. Spherical volumes of interest were drawn over tumour, blood pool and organs to determine biodistribution and calculate dosimetry. In one participant, tumour specimens were analysed for cell death using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining.
Results: [ 68 Ga]Ga-CDI is safe and well-tolerated with no side effects or adverse events. [ 68 Ga]Ga-CDI is renally excreted, demonstrates low levels of physiologic uptake in the other organs and has excellent imaging characteristics. The mean effective dose was 2.17E - 02 ± 4.61E - 03 mSv/MBq. It images constitutive tumour cell death and correlates with tumour cell death on histology.
Conclusion: [ 68 Ga]Ga-CDI is a novel cell death imaging radiopharmaceutical that is safe, has low radiation dosimetry and excellent biodistribution and imaging characteristics. It has potential advantages over previously investigated radiopharmaceuticals for imaging of cell death and has progressed to a proof-of-concept trial.
Trial Registration: ACTRN12621000641897 (28/5/2021, retrospectively registered).
(© 2022. The Author(s).)
Databáze: MEDLINE
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