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Purpose: Preclinical imaging, with translational potential, lacks a standardized method for defining volumes of interest (VOIs), impacting data reproducibility. The aim of this study was to determine the interobserver variability of VOI sizes and standard uptake values (SUV mean and SUV max ) of different organs using the same [ 18 F]FDG-PET and PET/CT datasets analyzed by multiple observers. In addition, the effect of a standardized analysis approach was evaluated., Procedures: In total, 12 observers (4 beginners and 8 experts) analyzed identical preclinical [ 18 F]FDG-PET-only and PET/CT datasets according to their local default image analysis protocols for multiple organs. Furthermore, a standardized protocol was defined, including detailed information on the respective VOI size and position for multiple organs, and all observers reanalyzed the PET/CT datasets following this protocol., Results: Without standardization, significant differences in the SUV mean and SUV max were found among the observers. Coregistering CT images with PET images improved the comparability to a limited extent. The introduction of a standardized protocol that details the VOI size and position for multiple organs reduced interobserver variability and enhanced comparability., Conclusions: The protocol offered clear guidelines and was particularly beneficial for beginners, resulting in improved comparability of SUV mean and SUV max values for various organs. The study suggested that incorporating an additional VOI template could further enhance the comparability of the findings in preclinical imaging analyses., (© 2024. The Author(s).)

Purpose: Multidrug resistance-associated proteins (MRPs) mediate the hepatobiliary and renal excretion of many drugs and drug conjugates. The positron emission tomography (PET) tracer 6-bromo-7-[ 11 C]methylpurine is rapidly converted in tissues by glutathione-S-transferases into its glutathione conjugate, and has been used to measure the activity of Abcc1 in the brain and the lungs of mice. Aim of this work was to investigate if the activity of MRPs in excretory organs can be measured with 6-bromo-7-[ 11 C]methylpurine., Procedures: We performed PET scans with 6-bromo-7-[ 11 C]methylpurine in groups of wild-type, Abcc4 (-/-) and Abcc1 (-/-) mice, with and without pre-treatment with the prototypical MRP inhibitor MK571., Results: 6-Bromo-7-[ 11 C]methylpurine-derived radioactivity predominantly underwent renal excretion. In blood, MK571 treatment led to a significant increase in the AUC and a decrease in the elimination rate constant of radioactivity (k elimination,blood ). In the kidneys, there were significant decreases in the rate constant for radioactivity uptake from the blood (k uptake,kidney ), k elimination,kidney , and the rate constant for tubular secretion of radioactivity (k urine ). Experiments in Abcc4 (-/-) mice indicated that Abcc4 contributed to renal excretion of 6-bromo-7-[ 11 C]methylpurine-derived radioactivity., Conclusions: Our data suggest that 6-bromo-7-[ 11 C]methylpurine may be useful to assess the activity of MRPs in the kidneys as well as in other organs (brain, lungs), although further work is needed to identify the MRP subtypes involved in the disposition of 6-bromo-7-[ 11 C]methylpurine-derived radioactivity.

Purpose: The application of radiolabelled inhibitors of cytochrome P450 enzymes is a novel approach for molecular imaging of adrenocortical masses to detect adrenal tumours. One potential tracer is radiolabelled iodometomidate (IMTO) with a common option for scintigraphic diagnosis and therapeutic applications. The aim of this study was to radiolabel iodometomidate with the positron-emitting radionuclide iodine-124 ((124)I) for the investigation of the biological behaviour and pharmacokinetics with positron emission tomography (PET)., Procedures: [(124)I]IMTO has been synthesized by oxidative radioiodo-destannylation, purified via semi-preparative HPLC and formulated in acetate-buffered saline, which contained ascorbic acid and ethanol to avoid radiolytic decomposition. Biological evaluation was performed in rats which received 5.5 ± 0.7 MBq [(124)I]IMTO in vivo. The radioactivity distribution (n = 3) has been dynamically imaged from 0-120 min after intravenous (i.v.) injection by small-animal PET. Regions of interest have been defined manually in the reconstructed PET images, and the activity concentration was expressed as percent injected dose per gram tissue (%ID/g)., Results: [(124)I]IMTO was prepared with a radiochemical yield of 83 ± 5 % (n = 3) and a radiochemical purity of >97 %. The final formulation of [(124)I]IMTO was stable for up to 48 h at room temperature. Two hours after i.v. administration in rats, radioactivity concentration in the adrenal glands were 2.1 ± 0.3 %ID/g, which was sufficient to achieve highest-contrast adrenal PET images., Conclusions: In the present study, the biological characteristics of radioiodinated metomidate were evaluated. [(124)I]IMTO appears as an attractive PET tracer for imaging of adrenals.

Purpose: The polysaccharide chitosan is a unique material for the design of ocular drug-delivery vehicles. The aim of this study was to radiolabel chitosan with iodine-124 ((124)I) for measurement of ocular pharmacokinetics in rabbits using small-animal positron emission tomography (PET)., Procedures: Crl:CHBB (HM) rabbits received one drop (35 µL) of either a formulation containing chitosan (0.5%, w/v) spiked with (124)I-labeled chitosan ([(124)I]chitosan) (n = 4) or a control solution of sodium [(124)I]iodide in buffer (n = 2) in the conjunctival sac of the right eye. Radioactivity distribution in the head region was measured at five different time points between 0 and 22 h after topical application. Regions of interest were manually defined in the reconstructed PET images, and activity concentration was quantified as percent applied dose (AD) per cubic centimeter tissue., Results: Clear differences were observed in the ocular pharmacokinetics of the two formulations. At 3 h after application, ocular activity uptake was 0.5 ± 0.1%AD/cc for sodium [(124)I]iodide, compared to 4.7 ± 5.3%AD/cc for the [(124)I]chitosan formulation., Conclusions: We were able to show that ocular pharmacokinetics of (124)I-labeled ophthalmic formulations can be measured with small-animal PET and that [(124)I]chitosan had approximately a 2-fold increased ocular retention through the study period compared to sodium [(124)I]iodide.

Purpose: We evaluated the usefulness of small animal brain positron emission tomography (PET) imaging with the amyloid-beta (A beta) probe 2-(1-{6-[(2-[(18)F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malonitrile ([(18)F]FDDNP) and with 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) for detection and quantification of pathological changes occurring in a transgenic mouse model of Alzheimer's disease (Tg2576 mice)., Procedures: [(18)F]FDDNP (n = 6) and FDG-PET scans (n = 3) were recorded in Tg2576 mice (age 13-15 months) and age-matched wild-type litter mates. Brain volumes of interest were defined by co-registration of PET images with a 3D MOBY digital mouse phantom. Regional [(18)F]FDDNP retention in mouse brain was quantified in terms of the relative distribution volume (DVR) using Logan's graphical analysis with cerebellum as a reference region., Results: Except for a lower maximum brain uptake of radioactivity in transgenic animals, the regional brain kinetics as well as DVR values of [(18)F]FDDNP appeared to be similar in both groups of animals. Also for FDG, regional radioactivity retention was almost identical in the brains of transgenic and control animals., Conclusions: We could not detect regionally increased [(18)F]FDDNP binding and regionally decreased FDG binding in the brains of Tg2576 transgenic versus wild-type mice. However, small group differences in signal might have been masked by inter-animal variability. In addition, technical limitations of the applied method (partial volume effect, spatial resolution) for measurements in such small organs as mouse brain have to be taken into consideration.