18F-Fluorothymidine radiation dosimetry in human PET imaging studies.

3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a PET imaging agent that shows promise for studying cellular proliferation in human cancers. FLT is a nucleoside analog that enters cells and is phosphorylated by human thymidine kinase 1, but the 3' substitution prevents further incorporation into DNA. We estimated the radiation dosimetry for this tracer from data gathered in patient studies. METHODS: Time-dependent tissue concentrations of radioactivity were determined from blood samples and PET images of 18 patients after intravenous injection of (18)F-FLT. Radiation-absorbed doses were calculated using the MIRD Committee methods, taking into account variations that were based on the distribution of activities observed in the individual patients. Effective dose equivalent (EDE) was calculated using International Commission on Radiological Protection Publication 60 tissue weighting factors for the standard man and woman. RESULTS: For a single bladder voiding at 6 h after (18)F-FLT injection, the (18)F-FLT EDE (mean +/- SD) was 0.028 +/- 0.012 mSv/MBq (103 +/- 43 mrem/mCi) for a standard male patient and 0.033 +/- 0.012 mSv/MBq (121 +/- 43 mrem/mCi) for a standard female patient. The organ that received the highest dose was the bladder (male, 0.179 mGy/MBq [662 mrad/mCi]; female, 0.174 mGy/MBq [646 mrad/mCi]), followed by the liver (male, 0.045 mGy/MBq [167 mrad/mCi]; female, 0.064 mGy/MBq [238 mrad/mCi]), the kidneys (male, 0.035 mGy/MBq [131 mrad/mCi]; female, 0.042 mGy/MBq [155 mrad/mCi]), and the bone marrow (male, 0.024 mGy/MBq [89 mrad/mCi]; female, 0.033 mGy/MBq [122 mrad/mCi]). CONCLUSION: Organ dose estimates for (18)F-FLT are comparable to those associated with other commonly performed nuclear medicine tests, and the potential radiation risks associated with (18)F-FLT PET imaging are within accepted limits.     

18F]fluoroestradiol radiation dosimetry in human PET studies.

[18F]16alpha-fluoroestradiol (FES) is a PET imaging agent useful for the study of estrogen receptors in breast cancer. We estimated the radiation dosimetry for this tracer using data obtained in patient studies. METHODS: Time-dependent tissue concentrations of radioactivity were determined from blood samples and PET images in 49 patients (52 studies) after intravenous injection of FES. Radiation absorbed doses were calculated using the procedures of the MIRD committee, taking into account the variation in dose based on the distribution of activities observed in the individual patients. Effective dose equivalent was calculated using International Commission on Radiological Protection Publication 60 weights for the standard woman. RESULTS: The effective dose equivalent was 0.022 mSv/MBq (80 mrem/mCi). The organ that received the highest dose was the liver (0.13 mGy/MBq [470 mrad/mCi]), followed by the gallbladder (0.10 mGy/MBq [380 mrad/mCi]) and the urinary bladder (0.05 mGy/MBq [190 mrad/mCi]). CONCLUSION: The organ doses are comparable to those associated with other commonly performed nuclear medicine tests. FES is a useful estrogen receptor-imaging agent, and the potential radiation risks associated with this study are well within accepted limits.     

Pharmacokinetics and radiation dosimetry of 18F-fluorocholine.

18F-Fluorocholine (fluoromethyl-dimethyl-2-hydroxyethylammonium [FCH]) has been developed as an oncologic probe for PET. This study evaluates the kinetics and radiation dosimetry of 18F-FCH using murine and human biodistribution data. METHODS: The biodistribution of 18F-FCH was obtained at time points up to 10 h after administration in control and tumor-bearing anesthetized nude mice. Human biodistribution data within the first hour after injection were obtained from attenuation-corrected whole-body PET scans of male (n = 7) and female (n = 5) cancer patients. Radiation dosimetry estimates were calculated using the murine and human biodistribution data assuming no redistribution of tracer after 1 h. RESULTS: Rapid pharmacokinetics were observed for 18F-FCH in mice and humans. The biodistribution is nearly static after 10 min. The dose-critical organ is the kidney, which receives 0.17 +/- 0.05 and 0.16 +/- 0.07 mSv/MBq (0.64 +/- 0.18 and 0.55 +/- 0.32 rad/mCi) for females and males, respectively. The effective dose equivalent (whole body) from administration of 4.07 MBq/kg (0.110 mCi/kg) is approximately 0.01 Sv for females and males. CONCLUSION: 18F-FCH is rapidly cleared from the circulation and its biodistribution changes very slowly at >10 min after administration. The kidney is the dose-critical organ and limits administration levels of 18F-FCH to 4.07 MBq/kg (0.110 mCi/kg) in human research studies.     

PET-based radiation dosimetry in man of 18F-fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer.

16 beta-fluoro-5 alpha-dihydrotestosterone (FDHT) is a promising new PET radiopharmaceutical for the imaging of prostate cancer. A recent clinical trial provided the opportunity for refinement of normal-tissue radiation-absorbed dose estimates based on quantitative PET. The objective of the current study was to derive estimates of normal-tissue absorbed doses for (18)F-FDHT administered to patients with advanced prostate cancer. METHODS: Absorbed dose estimates were derived from 10 (18)F-FDHT PET studies (administered activity, 111-407 MBq) of 7 prostate cancer patients. Activity concentrations in plasma and red marrow (assuming a plasmacrit of 0.58, an extracellular fluid fraction of 0.40, and equilibration of activity between plasma and marrow extracellular fluid) were measured ex vivo from a peripheral blood sample. Liver, spleen, urinary bladder contents, and total-body activities were measured by region-of-interest analysis of quantitative whole-body studies acquired with a dedicated PET scanner. Total organ activities and residence times were calculated from the respective PET scan-derived activity concentrations assuming standard (70 kg) man organ masses. Urinary excretion was corrected for hepatobiliary excretion (liver activity), and a first-order adjustment was made for the bladder-wall mass based on the patient's total-body mass. Mean organ absorbed doses were calculated with the MIRD formalism and the standard man model using the MIRDOSE3 software program. RESULTS: The absorbed doses (mean +/- SD) ranged from 0.00057 +/- 0.000281 cGy/MBq (to skin) to 0.00868 +/- 0.00481 cGy/MBq (to bladder wall) (voiding intervals, 1-2 h), and the effective dose equivalent was 0.00177 +/- 0.000152 cSv/MBq. CONCLUSION: The maximum absorbed dose among all tissues in all 10 studies, 0.0151 cGy/MBq, occurred for the urinary bladder wall (with hydration and 1- to 2-h voiding intervals). To ensure that the maximum normal-tissue absorbed dose is kept below the recommended maximum permissible dose of 5 cGy per single administration, a maximum administered activity of 331 MBq (5 cGy/[0.0151 cGy/MBq]) is recommended for (18)F-FDHT.     

Biodistribution and radiation dosimetry of 18F-fluoro-A-85380 in healthy volunteers.

This study reports on the biodistribution and radiation dosimetry of 2-(18)F-Fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine ((18)F-fluoro-A-85380), a promising radioligand for the imaging of central nicotinic acetylcholine receptors (nAChRs). METHODS: Whole-body scans were performed in 3 healthy male volunteers up to 2 h after intravenous injection of 137-238 MBq (18)F-fluoro-A-85380. Transmission scans (3 min per step, 8 or 9 steps according to the height of the subject) in 2-dimensional mode were used for subsequent correction of attenuation of emission scans. Emission scans (1 min per step) were acquired over 2 h. Venous blood samples were taken up to 2 h after injection of the radiotracer. Urine was freely collected up to 2 h after injection of the radiotracer. For each subject, the percentage of injected activity measured in regions of interest over brain, intestine, stomach, bladder, kidneys, and liver were fitted to a monoexponential model, as an uptake phase followed by a monoexponential washout, or to a biexponential model to generate time-activity curves. Using the MIRD method, ten source organs were considered in estimating radiation absorbed doses for organs of the body. RESULTS: Injection of (18)F-fluoro-A-85380 was clinically well tolerated and blood and urine pharmacologic parameters did not change significantly. The primary routes of clearance were renal and intestinal. Ten minutes after injection, high activities were observed in the bladder, kidneys, and liver. Slow uptake was seen in the brain. The liver received the highest absorbed dose. The average effective dose of (18)F-fluoro-A-85380 was estimated to be 0.0194 mSv/MBq. CONCLUSION: The amount of (18)F-fluoro-A-85380 required for adequate nAChR imaging results in an acceptable effective dose equivalent to the patient.     

Whole-body radiation dosimetry of 2-[18F]Fluoro-A-85380 in human PET imaging studies

2-[¹⁸F]Fluoro-A-85380 (2-[¹⁸F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine, 2-[¹⁸F]FA) is a recently developed PET radioligand for noninvasive imaging of nicotinic acetylcholine receptors. Previous radiation absorbed dose estimates for 2-[¹⁸F]FA were limited to evaluation of activity in only several critical organs. Here, we performed 2-[¹⁸F]FA radiation dosimetry studies on two healthy human volunteers to obtain data for all important body organs. Intravenous injection of 2.9 MBq/kg of 2-[¹⁸F]FA was followed by dynamic PET imaging. Regions of interest were placed over images of each organ to generate time–activity curves, from which we computed residence times. Radiation absorbed doses were calculated from the residence times using the MIRDOSE 3.0 program (version 3.0, ORISE, Oak Ridge, TN). The urinary bladder wall receives the highest radiation absorbed dose (0.153 mGy/MBq, 0.566 rad/mCi, for a 2.4-h voiding interval), followed by the liver (0.0496 mGy/MBq, 0.184 rad/mCi) and the kidneys (0.0470 mGy/MBq, 0.174 rad/mCi). The mean effective dose equivalent is estimated to be 0.0278 mSv/MBq (0.103 rem/mCi), indicating that radiation dosimetry associated with 2-[¹⁸F]FA is within acceptable limits.     

Biodistribution and radiation dosimetry of [18F]F-PEB in nonhuman primates

INTRODUCTION: The metabotropic glutamate receptor subtype 5 (mGluR5) is distributed throughout the central nervous system (CNS), and has been suggested to be a potential target for several CNS disorders suchas Parkinson's disease, pain, anxiety, depression, schizophrenia, and addiction. We report here on the rhesus monkey biodistribution and radiation dosimetry of [F]3-fluoro-5-[(pyridine-3-yl)ethynyl]benzonitrile, [F]F-PEB, a mGluR5 positron emission tomography (PET) radiotracer. METHODS: Three male and two female rhesus monkeys were imaged using the Discovery ST PET/computed tomography scanner. A total of 25 whole body PET emissions were acquired over 3 h (23 emissions in one subject). Regions of interest were drawn in the brain, lungs, heart, liver, spleen, bladder, and testes. The absorbed radiation dose was calculated using OLINDA v1. RESULTS: At the end of the imaging session, 45% of the [F]F-PEB activity had been excreted by the liver and into the gastrointestinal tract and 10% had been excreted into the urinary bladder. When extrapolating to the adult human, the largest absorbed radiation doses were located in the upper large intestine (males: 0.18 mGy/MBq, females: 0.20 mGy/MBq) and small intestine (males: 0.16 mGy/MBq, females: 0.19 mGy/MBq). Effective radiation dose was 0.033 mSv/MBq for males and 0.034 mSv/MBq for females, similar to many other [F] ligands. CONCLUSION: The effective radiation dose of [F]F-PEB obtained from rhesus is similar to many other clinically utilized [F] ligands.     

Medical radiation dosimetry

Current dose measuring practices in the diagnostic and therapeutic use of radiation are reviewed. Radiation doses typically received by patients from diagnostic X-ray studies, including mammography and computerized axial tomography, are presented. Modern-day radiation therapy, both with conventional photons and with electrons and high-LET particles, emphasizes the need for accurate dosimetry. The different methods of beam calibration and dosimetry intercomparisons for the variety of radiation beams are discussed. Results of several important dosimetry intercomparisons are also presented.     

Biodistribution and radiation dosimetry of the synthetic nonmetabolized amino acid analogue anti-18F-FACBC in humans.

The synthetic leucine amino acid analog anti-1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid (anti-(18)F-FACBC) is a recently developed ligand that permits the evaluation of the L-amino acid transport system. This study evaluated the whole-body radiation burden of anti-(18)F-FACBC in humans. METHODS: Serial whole-body PET/CT scans of 6 healthy volunteers (3 male and 3 female) were acquired for 2 h after a bolus injection of anti-(18)F-FACBC (366 +/- 51 MBq). Organ-specific time-activity curves were extracted from the reconstructed data and integrated to evaluate the individual organ residence times. A uniform activity distribution was assumed in the body organs with urine collection after the study. Estimates of radiation burden to the human body were calculated on the basis of the recommendations of the MIRD committee. The updated dynamic bladder model was used to calculate dose to the bladder wall. RESULTS: All volunteers showed initially high uptake in the pancreas and liver, followed by rapid clearance. Skeletal muscle and bone marrow showed lower and prolonged uptake, with clearance dominated by the tracer half-life. The liver was the critical organ, with a mean absorbed dose of 52.2 microGy/MBq. The estimated effective dose was 14.1 microSv/MBq, representing less than 20% of the dose limit recommended by the Radioactive Drug Research Committee for a 370-MBq injection. Bladder excretion was low and initially observed 6 min after injection, well after peak tracer uptake in the body organs. CONCLUSION: The PET whole-body dosimetry estimates indicate that an approximately 370-MBq injection of anti-(18)F-FACBC yields good imaging and acceptable dosimetry. The nonmetabolized nature of this tracer is favorable for extraction of relevant physiologic parameters from kinetic models.     

Biodistribution and radiation dosimetry of 11C-labelled docetaxel in cancer patients

Purpose  

Docetaxel is an important chemotherapeutic agent used for the treatment of several cancer types. As radiolabelled anticancer agents provide a potential means for personalized treatment planning, docetaxel was labelled with the positron emitter ¹¹C. Non-invasive measurements of [¹¹C]docetaxel uptake in organs and tumours may provide additional information on pharmacokinetics and pharmacodynamics of the drug docetaxel. The purpose of the present study was to determine the biodistribution and radiation absorbed dose of [¹¹C]docetaxel in humans.     

Quantitative SPECT in radiation dosimetry

Accurate and precise radiation dosimetry is critical for the successful therapeutic application of systemically administered radionuclides, including, of course, radionuclides in the form of radiolabeled antibody. This requires determination, based on discrete serial measurements, of the time-dependent concentrations and/or total amounts of radioactivity in situ in order to calculate source region cumulated activities. Based on extensive studies (with clinically realistic numbers of counts and accuracies of the order of 10%) in simple geometric phantoms, in complex anthropomorphic phantoms, in animal models, and in humans, quantitative rotating scintillation camera-based single-photon emission computed tomography (SPECT) now appears to be a practical approach to such measurements. The basis of the quantitative imaging capability of a three-dimensional imaging modality such as SPECT is the elimination in the reconstructed image of counts emanating from activity surrounding the source region. Subject to considerations such as the reconstruction algorithm, attenuation and scatter corrections, and, most importantly, statistical uncertainty, the counts in a pixel in a reconstructed image are therefore directly proportional to the actual counts emanating from the corresponding voxel in situ. Among intrinsic, pre-processing, and post-processing attenuation corrections, post-processing algorithms, the most widely used approach in current commercial SPECT systems, have proven adequate in uniformly attenuating parts of the body (eg, abdomen, pelvis), subject to accurate delineation of the body contour. Although a number of sophisticated scatter correction methods have been developed, the lack of explicit scatter correction has, in practice, not been a major impediment to reasonably accurate quantitative SPECT imaging, despite scattered radiation representing up to 50% of the counts in a large source region (eg, liver). Because of its mathematical propagation in the image reconstruction process, statistical uncertainty (ie, "noise") in SPECT is far greater than would be expected if it were distributed according to Poisson statistics, as in planar imaging. The low "single slice" sensitivity of rotating scintillation camera-based SPECT is therefore the principal limitation of practical quantitative SPECT. Accordingly, absolute quantitation of count-limited clinical images has been accomplished using a judiciously selected "non-ramp" filter function. In summary, reasonable quantitative SPECT imaging is now feasible clinically, even without sophisticated scatter corrections, at least in uniformly attenuating parts of the body.(ABSTRACT TRUNCATED AT 400 WORDS)     

Beta-particle dosimetry in radiation synovectomy

Beta-particle dosimetry of various radionuclides used in the treatment of rheumatoid arthritis was estimated using Monte Carlo radiation transport simulation coupled with experiments using reactor-produced radionuclides and radiachromic film dosimeters inserted into joint phantoms and the knees of cadavers. Results are presented as absorbed dose factors (cGy-cm²/MBq-s) versus depth in a mathematical model of the rheumatoid joint which includes regions of bone, articular cartilage, joint capsule, and tissue (synovium) found in all synovial joints. The factors can be used to estimate absorbed dose and dose rate distributions in treated joints. In particular, guidance is provided for those interested in (a) a given radionuclide's therapeutic range, (b) the amount of radioactivity to administer on a case-by-case basis, (c) the expected therapeutic dose to synovium, and (d) the radiation dose imparted to other, nontarget components in the joint, including bone and articular cartilage.     

Reduction of doses in teleradiography of the spine. Criteria of radiation protection and studies of dosimetry

To reduce the radiation exposure during full spine X-ray examinations, the following techniques were instituted: 72" tube to film distance; X-ray beam collimation; fast screen-film combination (rare earth gradual screens with high speed films); additional compensation filters; shielding of the most radiation-sensitive organs. Dosimetric measurements are reported. A very high reduction in exposure, above all of breasts and gonads, was obtained, without significant loss in the quality of radiographs.     

Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[18F]-ADAM in rats and monkeys

Purpose  

4-[¹⁸F]-ADAM is a potent serotonin transport imaging agent. We studied its toxicity in rats and radiation dosimetry in monkeys before human studies are undertaken.     

Whole-body biodistribution and radiation dosimetry of the human cannabinoid type-1 receptor ligand 18F-MK-9470 in healthy subjects.

The cannabinoid type-1 (CB1) receptor is one of the most abundant G-coupled protein receptors in the human body and is responsible for signal transduction of both endogenous and exogenous cannabinoids. The endocannabinoid system is strongly implicated in regulation of homeostasis and several neuropsychiatric disorders, obesity, and associated comorbidities, such as dyslipidemia and metabolic syndrome. We have used whole-body PET/CT to characterize the biodistribution and dosimetry of a novel high-affinity, subtype-selective radioligand, (18)F-MK-9470, in healthy male and female subjects. METHODS: Eight nonobese subjects (5 men, 3 women; age, 22-54 y) underwent serial whole-body PET/CT for 6 h after a bolus injection of 251 +/- 25 MBq (18)F-MK-9470 (N-[2-(3-cyano-phenyl)-3-(4-(2-(18)F-fluorethoxy)phenyl)-1-methylpropyl]-2-(5-methyl-2-pyridyloxy)-2-methylproponamide). Source organs were delineated 3-dimensionally using the combined morphologic and functional data. Residence times were derived from time-activity profiles using both the trapezoid rule and curve fitting. Individual organ doses and effective doses were determined using the OLINDA software package, with different approaches for gastrointestinal and urinary excretion modeling. RESULTS: (18)F-MK-9470 is taken up slowly in the brain, reaching a plateau at approximately 90-120 min after bolus injection and is excreted predominantly through the hepatobiliary system. The gallbladder, upper large intestine, small intestine, and liver are the organs with the highest absorbed dose (average: 159, 98, 87, and 86 microGy/MBq, respectively). The mean effective dose (ED) was 22.8 +/- 4.3 microSv/MBq, indicating relatively low intersubject variability and a mean value in the range of many commercially available (18)F-labeled radiopharmaceuticals. Brain uptake was relatively high compared with that of existing central nervous system ligands for other receptors, between 3.2% and 4.9% of the injected dose. CONCLUSION: The estimated radiation burden of (18)F-MK-9470 for PET CB1 receptor imaging shows relatively low variability between subjects and has an acceptable ED, which allows multiple serial cerebral scans of good image quality, while remaining within the risk category class II-b defined by the World Health Organization and the International Commission for Radiation Protection for a standard injected activity (185-370 MBq).