Dataset Information

Pancreatic uptake and radiation dosimetry of 6-[18F]fluoro-L-DOPA from PET imaging studies in infants with congenital hyperinsulinism.

ABSTRACT: After injecting 25.6 ± 8.8 MBq (0.7 ± 0.2 mCi) of 18F-Fluoro-L-DOPA intravenously, three static PET scans were acquired at 20, 30, and 40 min post injection in 3-D mode on 10 patients (6 male, 4 female) with congenital hyperinsulinism. Regions of interest (ROIs) were drawn over several organs visible in the reconstructed PET/CT images and time activity curves (TACs) were generated. Residence times were calculated using the TAC data. The radiation absorbed dose for the whole body was calculated by entering the residence times in the OLINDA/EXM 1.0 software.The mean residence times for the 18F-Fluoro-L-DOPA in the liver, lungs, kidneys, muscles, and pancreas were 11.54 ± 2.84, 1.25 ± 0.38, 4.65 ± 0.97, 17.13 ± 2.62, and 0.89 ± 0.34 min, respectively. The mean effective dose equivalent for 18F-Fluoro-L-DOPA was 0.40 ± 0.04 mSv/MBq. The CT scan used for attenuation correction delivered an additional radiation dose of 5.7 mSv. The organs receiving the highest radiation absorbed dose from 18F-Fluoro-L-DOPA were the urinary bladder wall (2.76 ± 0.95 mGy/MBq), pancreas (0.87 ± 0.30 mGy/MBq), liver (0.34 ± 0.07 mGy/MBq), and kidneys (0.61 ± 0.11 mGy/MBq). The renal system was the primary route for the radioactivity clearance and excretion.The estimated radiation dose burden from 18F-Fluoro-L-DOPA is relatively modest to newborns.

SUBMITTER: Garg PK

PROVIDER: S-EPMC5695579 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Pancreatic uptake and radiation dosimetry of 6-[18F]fluoro-L-DOPA from PET imaging studies in infants with congenital hyperinsulinism.

Garg Pradeep K PK Lokitz Stephen J SJ Truong Lisa L Putegnat Burton B Reynolds Courtney C Rodriguez Larry L Nazih Rachid R Nedrelow Jonathan J Guardia Miguel de la M Uffman John K JK Garg Sudha S Thornton Paul S PS

PloS one 20171108 11

<h4>Methods</h4>After injecting 25.6 ± 8.8 MBq (0.7 ± 0.2 mCi) of 18F-Fluoro-L-DOPA intravenously, three static PET scans were acquired at 20, 30, and 40 min post injection in 3-D mode on 10 patients (6 male, 4 female) with congenital hyperinsulinism. Regions of interest (ROIs) were drawn over several organs visible in the reconstructed PET/CT images and time activity curves (TACs) were generated. Residence times were calculated using the TAC data. The radiation absorbed dose for the whole body ...[more]

PMID: 29117181

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Project description:BACKGROUND:To facilitate hypoxia imaging in a clinical setting, we developed 1-(2,2-dihydroxymethyl-3-[18F]-fluoropropyl)-2-nitroimidazole ([18F]DiFA) as a new tracer that targets tumor hypoxia with its lower lipophilicity and efficient radiosynthesis. Here, we evaluated the radiation dosage, biodistribution, human safety, tolerability, and early elimination after the injection of [18F]DiFA in healthy subjects, and we performed a preliminary clinical study of patients with malignant tumors in a comparison with [18F]fluoromisonidazole ([18F]FMISO). RESULTS:The single administration of [18F]DiFA in 8 healthy male adults caused neither adverse events nor abnormal clinical findings. Dynamic and sequential whole-body scans showed that [18F]DiFA was rapidly cleared from all of the organs via the hepatobiliary and urinary systems. The whole-body mean effective dose of [18F]DiFA estimated by using the medical internal radiation dose (MIRD) schema with organ level internal dose assessment/exponential modeling (OLINDA/EXM) computer software 1.1 was 14.4 ± 0.7 μSv/MBq. Among the organs, the urinary bladder received the largest absorbed dose (94.7 ± 13.6 μSv/MBq). The mean absorbed doses of the other organs were equal to or less than those from other hypoxia tracers. The excretion of radioactivity via the urinary system was very rapid, reaching 86.4 ± 7.1% of the administered dose. For the preliminary clinical study, seven patients were subjected to [18F]FMISO and [18F]DiFA positron emission tomography (PET) at 48-h intervals to compare the two tracers' diagnostic ability for tumor hypoxia. The results of the tumor hypoxia evaluation by [18F]DiFA PET at 1 h and 2 h were not significantly different from those obtained with [18F]FMISO PET at 4 h ([18F]DiFA at 1 h, p = 0.32; [18F]DiFA at 2 h, p = 0.08). Moreover, [18F]DiFA PET at both 1 h (k = 0.68) and 2 h (k = 1.00) showed better inter-observer reproducibility than [18F]FMISO PET at 4 h (k = 0.59). CONCLUSION:[18F]DiFA is well tolerated, and its radiation dose is comparable to those of other hypoxia tracers. [18F]DiFA is very rapidly cleared via the urinary system. [18F]DiFA PET generated comparable images to [18F]FMISO PET in hypoxia imaging with shorter waiting time, demonstrating the promising potential of [18F]DiFA PET for hypoxia imaging and for a multicenter trial.

Project description:Combined whole-body dual-tracer ((18)F-FDG and (11)C-acetate) PET/CT is increasingly used for staging hepatocellular carcinoma, with only limited studies investigating the radiation dosimetry data of these scans. The aim of the study was to characterize the radiation dosimetry of combined whole-body dual-tracer PET/CT protocols.Consecutive adult patients with hepatocellular carcinoma who underwent whole-body dual-tracer PET/CT scans were retrospectively reviewed with institutional review board approval. OLINDA/EXM 1.1 was used to estimate patient-specific internal dose exposure in each organ. Biokinetic models for (18)F-FDG and (11)C-acetate as provided by ICRP (International Commission on Radiological Protection) publication 106 were used. Standard reference phantoms were modified to more closely represent patient-specific organ mass. With patient-specific parameters, organ equivalent doses from each CT series were estimated using VirtualDose. Dosimetry capabilities for tube current modulation protocols were applied by integrating with the latest anatomic realistic models. Effective dose was calculated using ICRP publication 103 tissue-weighting coefficients for adult male and female, respectively.Fourteen scans were evaluated (12 men, 2 women; mean age ± SD, 60 ± 19.48 y). The patient-specific effective dose from (18)F-FDG and (11)C-acetate was 6.08 ± 1.49 and 1.56 ± 0.47 mSv, respectively, for male patients and 6.62 ± 1.38 and 1.79 ± 0.12 mSV, respectively, for female patients. The patient-specific effective dose of the CT component, which comprised 2 noncontrast whole-body scans, to male and female patients was 21.20 ± 8.94 and 14.79 ± 3.35 mSv, respectively. Thus, the total effective doses of the combined whole-body dual-tracer PET/CT studies for male and female patients were 28.84 ± 10.18 and 23.19 ± 4.61 mSv, respectively.Patient-specific parameters allow for more accurate estimation of organ equivalent doses. Considering the substantial radiation dose incurred, judicious medical justification is required with every whole-body dual-tracer PET/CT referral. Although radiation risks may have less impact for the population with cancer because of their reduced life expectancy, the information is of interest and relevant for both justification, to evaluate risk/benefit, and protocol optimization.

Project description:Background[18F]UCB-H was developed as a novel radiotracer with a high affinity for synaptic vesicle protein 2A, the binding site for the antiepileptic levetiracetam. The objectives of this study were to evaluate the radiation dosimetry of [18F]UCB-H in a preclinical trial and to determine the maximum injectable dose according to guidelines for human biomedical research. The radiation dosimetry was derived by organ harvesting and dynamic micro positron emission tomography (PET) imaging in mice, and the results of both methods were compared.MethodsTwenty-four male C57BL-6 mice were injected with 6.96 ± 0.81 MBq of [18F]UCB-H, and the biodistribution was determined by organ harvesting at 2, 5, 10, 30, 60, and 120 min (n = 4 for each time point). Dynamic microPET imaging was performed on five male C57BL-6 mice after the injection of 9.19 ± 3.40 MBq of [18F]UCB-H. A theoretical dynamic bladder model was applied to simulate urinary excretion. Human radiation dose estimates were derived from animal data using the International Commission on Radiological Protection 103 tissue weighting factors.ResultsBased on organ harvesting, the urinary bladder wall, liver and brain received the highest radiation dose with a resulting effective dose of 1.88E-02 mSv/MBq. Based on dynamic imaging an effective dose of 1.86E-02 mSv/MBq was calculated, with the urinary bladder wall and liver (brain was not in the imaging field of view) receiving the highest radiation.ConclusionsThis first preclinical dosimetry study of [18F]UCB-H showed that the tracer meets the standard criteria for radiation exposure in clinical studies. The dose-limiting organ based on US Food and Drug Administration (FDA) and European guidelines was the urinary bladder wall for FDA and the effective dose for Europe with a maximum injectable single dose of approximately 325 MBq was calculated. Although microPET imaging showed significant deviations from organ harvesting, the Pearson's correlation coefficient between radiation dosimetry derived by either method was 0.9666.

Project description:UNLABELLED:2-((2S,5R,8S,11S)-5-benzyl-8-(4-((2S,3R,4R,5R,6S)-6-((2-(4-(3-(18)F-fluoropropyl)-1H-1,2,3-triazol-1-yl)acetamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxamido)butyl)-11-(3-guanidinopropyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaazacyclopentadecan-2-yl)acetic acid ((18)F-RGD-K5) has been developed as an ?(v)?(3) integrin marker for PET. The purpose of this study was to determine the biodistribution and estimate the radiation dose from (18)F-RGD-K5 using whole-body PET/CT scans in monkeys and humans. METHODS:Successive whole-body PET/CT scans were obtained after intravenous injection of (18)F-RGD-K5 in 3 rhesus monkeys (167 ± 19 MBq) and 4 healthy humans (583 ± 78 MBq). In humans, blood samples were collected between the PET/CT scans, and stability of (18)F-RGD-K5 was assessed. Urine was also collected between the scans, to determine the total activity excreted in urine. 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 human and monkey biodistributions. RESULTS:(18)F-RGD-K5 was metabolically stable in human blood up to 90 min after injection, and it cleared rapidly from the blood pool, with a 12-min half-time. For both monkeys and humans, increased (18)F-RGD-K5 uptake was observed in the kidneys, bladder, liver, and gallbladder, with mean standardized uptake values at 1 h after injection for humans being approximately 20, 50, 4, and 10, respectively. For human biodistribution data, the calculated effective dose was 31 ± 1 ?Sv/MBq, and the urinary bladder wall had the highest absorbed dose at 376 ± 19 ?Gy/MBq using the 4.8-h bladder-voiding model. With the 1-h voiding model, these doses reduced to 15 ± 1 ?Sv/MBq for the effective dose and 103 ± 4 ?Gy/MBq for the absorbed dose in the urinary bladder wall. For a typical injected activity of 555 MBq, the effective dose would be 17.2 ± 0.6 mSv for the 4.8-h model, reducing to 8.3 ± 0.4 mSv for the 1-h model. For monkey biodistribution data, the effective dose to humans would be 22.2 ± 2.4 mSv for the 4.8-h model and 12.8 ± 0.2 mSv for the 1-h model. CONCLUSION:The biodistribution profile of (18)F-RGD-K5 in monkeys and humans was similar, with increased uptake in the bladder, liver, and kidneys. There was rapid clearance of (18)F-RGD-K5 through the renal system. The urinary bladder wall received the highest radiation dose and was deemed the critical organ. Both whole-body effective dose and bladder dose can be reduced by more frequent voiding. (18)F-RGD-K5 can be used safely for imaging ?(v)?(3) integrin expression in humans.

Project description:PURPOSE:Beta-secretase 1 (BACE1) enzyme is implicated in the pathophysiology of Alzheimer's disease. [18F]PF-06684511 is a positron emission tomography (PET) radioligand for imaging BACE1. Despite favorable brain kinetic properties, the effective dose (ED) of [18F]PF-06684511 estimated in non-human primates was relatively high. This study was therefore designed to evaluate the whole-body distribution, dosimetry, quantification, and test-retest reliability of imaging brain BACE1 with [18F]PF-06684511 in healthy volunteers. METHODS:Five subjects were studied for the dosimetry study. Whole-body PET was performed for 366 min with 4 PET-CT sessions. Estimates of the absorbed radiation dose were calculated using the male adult model. Eight subjects participated in the test-retest study. Brain PET measurements were conducted for 123 min with an interval of 5 to 19 days between test and retest conditions. The total distribution volume (VT) was estimated with one-tissue (1T), two-tissue (2T), compartment model (CM), and graphical analysis. Test-retest variability (TRV) and intraclass correlation coefficient (ICC) of VT were calculated as reliability measures. RESULTS:In the dosimetry study, the highest uptake was found in the liver (25.2?±?2.3 %ID at 0.5 h) and the largest dose was observed in the pancreas (92.9?±?52.2 ?Sv/MBq). The calculated ED was 24.7?±?0.8 ?Sv/MBq. In the test-retest study, 2TCM described the time-activity curves well. VT (2TCM) was the highest in the anterior cingulate cortex (6.28?±?1.09 and 6.85?±?0.81) and the lowest in the cerebellum (4.23?±?0.88 and 4.20?±?0.75). Mean TRV and ICC of VT (2TCM) were 16.5% (12.4-20.5%) and 0.496 (0.291-0.644). CONCLUSION:The ED of [18F]PF-06684511 was similar to other 18F radioligands, allowing repeated PET measurements. 2TCM was the most appropriate quantification method. TRV of VT was similar to other radioligands without a reference region, albeit with lower ICC. These data indicated that [18F]PF-06684511 is a suitable radioligand to measure BACE1 level in the human brain. TRIAL REGISTRATION:EudraCT 2016-001110-19 (registered 2016-08-08).

Dataset Information

Pancreatic uptake and radiation dosimetry of 6-[18F]fluoro-L-DOPA from PET imaging studies in infants with congenital hyperinsulinism.

Publications

Pancreatic uptake and radiation dosimetry of 6-[18F]fluoro-L-DOPA from PET imaging studies in infants with congenital hyperinsulinism.

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