Dataset Information

Biodistribution and radiation dosimetry of the integrin marker 18F-RGD-K5 determined from whole-body PET/CT in monkeys and humans.

ABSTRACT: 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.

SUBMITTER: Doss M

PROVIDER: S-EPMC7607669 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Biodistribution and radiation dosimetry of the integrin marker 18F-RGD-K5 determined from whole-body PET/CT in monkeys and humans.

Doss Mohan M Kolb Hartmuth C HC Zhang James J JJ Bélanger Marie-José MJ Stubbs James B JB Stabin Michael G MG Hostetler Eric D ED Alpaugh R Katherine RK von Mehren Margaret M Walsh Joseph C JC Haka Michael M Mocharla Vani P VP Yu Jian Q JQ

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20120412 5

<h4>Unlabelled</h4>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 α(v)β(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 P ...[more]

PMID: 22499613

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Project description:UNLABELLED:(18)F-CP-18, or (18S,21S,24S,27S,30S)-27-(2-carboxyethyl)-21-(carboxymethyl)-30-((2S,3R,4R,5R,6S)-6-((2-(4-(3-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-dioic acid, 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 whole-body 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 ± 4 ?Sv/MBq, with the urinary bladder wall having the highest absorbed dose at 536 ± 61 ?Gy/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 ± 2 ?Sv/MBq and 142 ± 15 ?Gy/MBq, respectively. For a typical injected activity of 555 MBq, the effective dose would be 21.1 ± 2.2 mSv for the 4.8-h interval, reduced to 8.3 ± 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.

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:BackgroundOur aim was to measure the impact of two cycles of standard chemotherapy on tumoural neoangiogenesis by [18F] fluorine arginine-glycine-aspartic (RGD-K5) positron emission tomography-computed tomography (PET) on patients presenting with lymphoma. Nineteen patients at Rouen's Henri Becquerel Cancer Centre were prospectively included. Fluorodeoxyglucose (FDG) and RGD-K5 PET were performed before (C0) and after (C2) two cycles of chemotherapy. End-of-treatment FDG PET was performed for final evaluation. Maximum standardised uptake value (SUVmax), SUVmean, Metabolic Tumour Volume (MTV) and Angiogenic Tumour Volume (ATV) were measured for all lesions. RGD SUVmax and SUVmean were also analysed in 13 normal organs at C0 and C2. The patient's treatment response was considered using the Deauville score (DS) at the end of FDG PET treatment (DS 1-3 were considered responders, and 4 and 5 non-responders).ResultsEighteen patients had both C0 FDG and RGD PET. Twelve patients had both C2 FDG and RGD, completed the treatment protocol and were included in end-of-treatment analysis. No statistical difference was found in RGD uptake of normal organs before and after chemotherapy for SUVmax and SUVmean. On C0 RGD, apart from classical Hodgkin lymphoma (cHL; n = 5) and grey zone lymphoma (GZL; n = 1), other lymphoma sub-types (n = 12) had low RGD uptake (p < 0.001). Regarding FDG, there was no significant difference for SUVmax, SUVmean and MTV at C0 and C2 between patients with cHL and non-Hodgkin lymphoma (NHL). At C2 RGD, non-responders had higher SUVmax and SUVmean compared to responders (p < 0.001). There was no significant difference in RGD ATV between responders and non-responders.ConclusionsOur study showed significant higher initial RGD uptake in patients presenting with cHL and GZL compared to NHL. Non-responder also had higher post-chemotherapy RGD uptake compared to responders. Issues raised by RGD uptake, particularly in cHL, are yet to be explored and need to be confirmed in a larger population.

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.

Dataset Information

Biodistribution and radiation dosimetry of the integrin marker 18F-RGD-K5 determined from whole-body PET/CT in monkeys and humans.

Publications

Biodistribution and radiation dosimetry of the integrin marker 18F-RGD-K5 determined from whole-body PET/CT in monkeys and humans.

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