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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-[ 11 C]methylpurine ([ 11 C]BMP) has been used to measure MRP1 function in rodents. In this study, [ 11 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 [ 11 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 E , h - 1 ) 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 E and corresponding TRTV values were: cerebral cortex: 0.055 ± 0.010 h - 1 (- 4 ± 24%), cerebellum: 0.033 ± 0.009 h - 1 (1 ± 39%), choroid plexus: 0.292 ± 0.059 h - 1 (0.1 ± 16%), retina: 0.234 ± 0.045 h - 1 (30 ± 38%), lungs: 0.875 ± 0.095 h - 1 (- 3 ± 11%), myocardium: 0.641 ± 0.105 h - 1 (11 ± 25%), kidneys: 1.378 ± 0.266 h - 1 (14 ± 16%), and liver: 0.685 ± 0.072 h - 1 (7 ± 9%). Significant sex differences were found for k E 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 [ 11 C]BMP potentially allows for simultaneous assessment of MRP function in multiple human tissues. Mean TRTV of k E in different tissues was in an acceptable range, except for the retina. The radiation dosimetry of [ 11 C]BMP was in the typical range of 11 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., (© 2024. The Author(s).)

Purpose: Risk classification of primary prostate cancer in clinical routine is mainly based on prostate-specific antigen (PSA) levels, Gleason scores from biopsy samples, and tumor-nodes-metastasis (TNM) staging. This study aimed to investigate the diagnostic performance of positron emission tomography/magnetic resonance imaging (PET/MRI) in vivo models for predicting low-vs-high lesion risk (LH) as well as biochemical recurrence (BCR) and overall patient risk (OPR) with machine learning., Methods: Fifty-two patients who underwent multi-parametric dual-tracer [ 18 F]FMC and [ 68 Ga]Ga-PSMA-11 PET/MRI as well as radical prostatectomy between 2014 and 2015 were included as part of a single-center pilot to a randomized prospective trial (NCT02659527). Radiomics in combination with ensemble machine learning was applied including the [ 68 Ga]Ga-PSMA-11 PET, the apparent diffusion coefficient, and the transverse relaxation time-weighted MRI scans of each patient to establish a low-vs-high risk lesion prediction model (M LH ). Furthermore, M BCR and M OPR predictive model schemes were built by combining M LH , PSA, and clinical stage values of patients. Performance evaluation of the established models was performed with 1000-fold Monte Carlo (MC) cross-validation. Results were additionally compared to conventional [ 68 Ga]Ga-PSMA-11 standardized uptake value (SUV) analyses., Results: The area under the receiver operator characteristic curve (AUC) of the M LH model (0.86) was higher than the AUC of the [ 68 Ga]Ga-PSMA-11 SUV max analysis (0.80). MC cross-validation revealed 89% and 91% accuracies with 0.90 and 0.94 AUCs for the M BCR and M OPR models respectively, while standard routine analysis based on PSA, biopsy Gleason score, and TNM staging resulted in 69% and 70% accuracies to predict BCR and OPR respectively., Conclusion: Our results demonstrate the potential to enhance risk classification in primary prostate cancer patients built on PET/MRI radiomics and machine learning without biopsy sampling.

Purpose: PET/MRI has recently been introduced into clinical practice. We prospectively investigated the clinical impact of PET/MRI compared with PET/CT, in a mixed population of cancer patients, and performed an economic evaluation of PET/MRI., Methods: Cancer patients referred for routine staging or follow-up by PET/CT underwent consecutive PET/CT and PET/MRI, using single applications of [ 18 F]FDG, [ 68 Ga]Ga-DOTANOC, or [ 18 F]FDOPA, depending on tumor histology. PET/MRI and PET/CT were rated separately, and lesions were assessed per anatomic region; based on regions, per-examination and per-patient accuracies were determined. A simulated, multidisciplinary team meeting served as reference standard and determined whether differences between PET/CT and PET/MRI affected patient management. The McNemar tests were used to compare accuracies, and incremental cost-effectiveness ratios (ICERs) for PET/MRI were calculated., Results: Two hundred sixty-three patients (330 same-day PET/CT and PET/MRI examinations) were included. PET/MRI was accurate in 319/330 examinations and PET/CT in 277/330 examinations; the respective accuracies of 97.3% and 83.9% differed significantly (P < 0.001). The additional findings on PET/MRI-mainly liver and brain metastases-had implications for patient management in 21/263 patients (8.0%). The per-examination cost was 596.97 EUR for PET/MRI and 405.95 EUR for PET/CT. ICERs for PET/MRI were 14.26 EUR per percent of diagnostic accuracy and 23.88 EUR per percent of correctly managed patients., Conclusions: PET/MRI enables more appropriate management than PET/CT in a nonnegligible fraction of cancer patients. Since the per-examination cost is about 50% higher for PET/MRI than for PET/CT, a histology-based triage of patients to either PET/MRI or PET/CT may be meaningful.

Purpose: PET with (18)F-FDG has the potential to assess vascular macrophage metabolism. (18)F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel (18)F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of (18)F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques., Methods: The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with (18)F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUVmax) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target-to-blood ratios (TBRs, plaque to blood pool) were calculated., Results: Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUVmax values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3 ± 0.6 vs. 3.1 ± 0.6; P < 0.01), but were significantly correlated between PET/CT and PET/MRI (Spearman's r = 0.67, P < 0.01). In contrast, TBRmax values of plaque lesions were similar on PET/MRI and on PET/CT (2.2 ± 0.3 vs. 2.2 ± 0.3; P = 0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearman's r = 0.73, P < 0.01). Considering the increasing trend in SUVmax and TBRmax values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBRmax values may also be expected with PET/MRI compared with PET/CT., Conclusion: SUVmax and TBRmax values are widely accepted reference parameters for estimation of the radioactivity of atherosclerotic plaques on PET/CT. However, due to a systematic underestimation of SUVmax and TBRmax with PET/MRI, the optimal cut-off values indicating the presence of inflamed plaque tissue need to be newly defined for PET/MRI.