Biodistribution and Radiation Dosimetry of ¹⁸F-CP-18, a Potential Apoptosis Imaging Agent, as Determined from PET/CT Scans in Healthy Volunteers

Abstract

F18-fluoropropyl)-1H-1,2,3-triazol-1-yl)acetamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxamido)- 24-isopropyl-18-methyl-17,20,23,26, 29-pentaoxo-4,7,10,13-tetraoxa-16,19,22,25,28-pentaazadotriacontane-1,32-dioicacid, is being evaluated as a tissue apoptosis marker for PET imaging. The purpose of this study was to determine the biodistribution and estimate the normal-organ radiation-absorbed doses and effective dose from 18 F-CP-18. Methods: Successive wholebody PET/CT scans were obtained at approximately 7, 45, 90, 130, and 170 min after intravenous injection of 18 F-CP-18 in 7 healthy human volunteers. Blood samples and urine were collected between the PET/CT scans, and the biostability of 18 F-CP-18 was assessed using high-performance liquid chromatography. The PET scans were analyzed to determine the radiotracer uptake in different organs. OLINDA/EXM software was used to calculate human radiation doses based on the biodistribution of the tracer. Results: 18 F-CP-18 was 54% intact in human blood at 135 min after injection. The tracer cleared rapidly from the blood pool with a half-life of approximately 30 min. Relatively high 18 F-CP-18 uptake was observed in the kidneys and bladder, with diffuse uptake in the liver and heart. The mean standardized uptake values (SUVs) in the bladder, kidneys, heart, and liver at around 50 min after injection were approximately 65, 6, 1.5, and 1.5, respectively. The calculated effective dose was 38 6 4 mSv/MBq, with the urinary bladder wall having the highest absorbed dose at 536 6 61 mGy/MBq using a 4.8-h bladder-voiding interval for the male phantom. For a 1-h voiding interval, these doses were reduced to 15 6 2 mSv/MBq and 142 6 15 mGy/MBq, respectively. For a typical injected activity of 555 MBq, the effective dose would be 21.1 6 2.2 mSv for the 4.8-h interval, reduced to 8.3 6 1.1 mSv for the 1-h interval. Conclusion: 18 F-CP-18 cleared rapidly through the renal system. The urinary bladder wall received the highest radiation dose and was deemed the critical organ. Both the effective dose and the bladder dose can be reduced by frequent voiding. From the radiation dosimetry perspective, the apoptosis imaging agent 18 F-CP-18 is suitable for human use.

In Vivo Imaging of Human Neuroinflammation

“…18 F-ML-10 is a derivative of the Aposense family of apoptotic markers 127 . 18 F-ICMT-11 and 18 F-CP-18 are both specific to caspase-3, a crucial enzyme for initiation of apoptosis 128, 129 . Each of these tracers has received safety validation in healthy controls, but none have yet been used to study neuroinflammatory disorders.…”

Rituximab or irradiation promotes IL-17 secretion and thereby induces resistance to rituximab or irradiation

“…Changes in the TME are among the major mechanisms of tumor cell resistance to radiation injury. 8 IL-17A has an important role in DLBCL tumorigenesis. We recently explored the distributions of immune cells and cytokine profiles in extranodal tumor lesions and their adjacent benign tissues in DLBCL patients.…”

Radiolabelled Peptides for Positron Emission Tomography and Endoradiotherapy in Oncology

“…The 18 F-labelled pentapeptide CP-18 is a substrate of caspase-3, which showed increased activity uptake in apoptotic thymi in mice [237]. Based on these promising findings, [ 18 F]F-CP-18 was studied in seven healthy volunteers [238]. The images showed uptake in the liver, heart, testes, kidneys, and bladder and due to the predominantly renal excretion, the critical organ in terms of dosimetry was the bladder wall.…”