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Article Abstract
Purpose: Multidrug resistance-associated protein 1 (MRP1) is a transport protein with a widespread tissue distribution, which has been implicated in the pathophysiology of Alzheimer's and chronic respiratory disease. PET with 6-bromo-7-[C]methylpurine ([C]BMP) has been used to measure MRP1 function in rodents. In this study, [C]BMP was for the first time characterised in humans to assess the function of MRP1 and other MRP subtypes in different tissues.
Methods: Thirteen healthy volunteers (7 men, 6 women) underwent dynamic whole-body PET scans on a long axial field-of-view (LAFOV) PET/CT system after intravenous injection of [C]BMP. Three subjects of each sex were scanned a second time to assess reproducibility. Volumes of interest were outlined for MRP-expressing tissues (cerebral cortex, cerebellum, choroid plexus, retina, lungs, myocardium, kidneys, and liver). From the time-activity curves, the elimination rate constant (k, h) was derived as a parameter for tissue MRP function and its test-retest variability (TRTV, %) was calculated. Radiation dosimetry was calculated using the Medical Internal Radiation Dose (MIRD) methodology.
Results: Mean k and corresponding TRTV values were: cerebral cortex: 0.055 ± 0.010 h (- 4 ± 24%), cerebellum: 0.033 ± 0.009 h (1 ± 39%), choroid plexus: 0.292 ± 0.059 h (0.1 ± 16%), retina: 0.234 ± 0.045 h (30 ± 38%), lungs: 0.875 ± 0.095 h (- 3 ± 11%), myocardium: 0.641 ± 0.105 h (11 ± 25%), kidneys: 1.378 ± 0.266 h (14 ± 16%), and liver: 0.685 ± 0.072 h (7 ± 9%). Significant sex differences were found for k in the cerebellum, lungs and kidneys. Effective dose was 4.67 ± 0.18 µSv/MBq for men and 4.55 ± 0.18 µSv/MBq for women.
Conclusion: LAFOV PET/CT with [C]BMP potentially allows for simultaneous assessment of MRP function in multiple human tissues. Mean TRTV of k in different tissues was in an acceptable range, except for the retina. The radiation dosimetry of [C]BMP was in the typical range of C-tracers. LAFOV PET/CT holds great potential to assess at a whole-body, multi-tissue level molecular targets relevant for drug disposition in humans.
Trial Registration: EudraCT 2021-006348-29. Registered 15 December 2021.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527933 | PMC |
| http://dx.doi.org/10.1007/s00259-024-06851-2 | DOI Listing |
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