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.     

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.     

1-11C-methyl-4-piperidinyl-N-butyrate radiation dosimetry in humans by dynamic organ-specific evaluation.

Deficits of cholinergic neurotransmission contribute to various neurologic and psychiatric conditions. The neurotransmitter acetylcholine is hydrolyzed in the synaptic clefts by 2 enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). 1-[(11)C]-Methyl-4-piperidinyl-N-butyrate ((11)C-MP4B) is a radioligand for the assessment study of BuChE activity in human brain with PET. In the present study the radiation-absorbed doses of the (11)C-MP4B were estimated in humans according to the guidelines of the International Commission on Radiological Protection. Two different data acquisition protocols-dynamic organ-specific evaluation (DOSE) and whole-body scanning-were compared. Both methods are widely used for evaluation of radiation burden of (11)C-labeled PET tracers. METHODS: Fixed-bed PET on the upper neck, thorax, abdomen, or pelvic region was performed on 7 healthy subjects after injection of 707 +/- 34 MBq (mean +/- SD) of (11)C-MP4B. Brain input was derived from our previous studies on 18 healthy control subjects and 10 patients with Alzheimer's disease. Regions of interest were drawn on transverse images of all visible organs. Radiation dose estimates were calculated from organ residence times using the MIRDOSE3 software. Urine samples were collected after imaging to estimate tracer extraction. To compare the estimates for absorbed doses between the whole-body scan approach and the DOSE method, we simulated whole-body data acquisition methods used in (11)C dosimetry studies with our fixed-bed data. RESULTS: The organs with the highest radiation-absorbed doses were the liver, urinary bladder, kidneys (renal cortex), upper large intestine, trabecular bone, salivary glands, and heart wall. Up to 60% of the injected dose was excreted via the urinary pathway, and the clearance was relatively rapid, as 30% of the radioactivity was excreted within 60 min after injection. With a 2-h voiding interval the effective dose was 4.2 microSv/MBq. CONCLUSION: (11)C-MP4B causes less radiation burden than previously studied (11)C-labeled PET tracers. No intolerably high absorbed doses were observed in critical organs. With 740 MBq of injected radioactivity, the radiation burden is equivalent to 3.11 mSv. This would allow multiple PET examinations per year to be performed on the same subject. The DOSE method and the simulated whole-body imaging approach produced similar results.     

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 <Superscript>68</Superscript>Ga-PSMA HBED CC—a PSMA specific probe for PET imaging of prostate cancer

Purpose

Positron emission tomography (PET) agents targeting the prostate-specific membrane antigen (PSMA) are currently under broad clinical and scientific investigation. ⁶⁸Ga-PSMA HBED-CC constitutes the first ⁶⁸Ga-labelled PSMA-inhibitor and has evolved as a promising agent for imaging PSMA expression in vivo. The aim of this study was to evaluate the whole-body distribution and radiation dosimetry of this new probe.

Methods

Five patients with a history or high suspicion of prostate cancer were injected intravenously with a mean of 139.8?±?13.7 MBq of ⁶⁸Ga-PSMA HBED-CC (range 120–158 MBq). Four static skull to mid-thigh scans using a whole-body fully integrated PET/MR-system were performed 10 min, 60 min, 130 min, and 175 min after the tracer injection. Time-dependent changes of the injected activity per organ were determined. Mean organ-absorbed doses and effective doses (ED) were calculated using OLINDA/EXM.

Results

Injection of a standard activity of 150 MBq ⁶⁸Ga-PSMA HBED-CC resulted in a median effective dose of 2.37 mSv (Range 1.08E-02 – 2.46E-02 mSv/MBq). The urinary bladder wall (median absorbed dose 1.64E-01 mGv/MBq; range 8.76E-02 – 2.91E-01 mGv/MBq) was the critical organ, followed by the kidneys (median absorbed dose 1.21E-01 mGv/MBq; range 7.16E-02 – 1.75E-01), spleen (median absorbed dose 4.13E-02 mGv/MBq; range 1.57E-02 – 7.32E-02 mGv/MBq) and liver (median absorbed dose 2.07E-02 mGv/MBq; range 1.80E-02 – 2.57E-02 mGv/MBq). No drug-related pharmacological effects occurred.

Conclusion

The use of ⁶⁸Ga-PSMA HBED-CC results in a relatively low radiation exposure, delivering organ doses that are comparable to those of other ⁶⁸Ga-labelled PSMA-inhibitors used for PET-imaging. Total effective dose is lower than for other PET-agents used for prostate cancer imaging (e.g. ¹¹C- and ¹⁸F-Choline).

     

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.     

Estimation of absorbed doses in humans due to intravenous administration of fluorine-18-fluorodeoxyglucose in PET studies

Radiation absorbed doses due to intravenous administration of fluorine-18-fluorodeoxyglucose in positron emission tomography (PET) studies were estimated in normal volunteers. The time-activity curves were obtained for seven human organs (brain, heart, kidney, liver, lung, pancreas, and spleen) by using dynamic PET scans and for bladder content by using a single detector. These time-activity curves were used for the calculation of the cumulative activity in these organs. Absorbed doses were calculated by the MIRD method using the absorbed dose per unit of cumulated activity, "S" value, transformed for the Japanese physique and the organ masses of the Japanese reference man. The bladder wall and the heart were the organs receiving higher doses of 1.2 x 10(-1) and 4.5 x 10(-2) mGy/MBq, respectively. The brain received a dose of 2.9 x 10(-2) mGy/MBq, and other organs received doses between 1.0 x 10(-2) and 3.0 x 10(-2) mGy/MBq. The effective dose equivalent was estimated to be 2.4 x 10(-2) mSv/MBq. These results were comparable to values of absorbed doses reported by other authors on the radiation dosimetry of this radiopharmaceutical.     

Dosimetry of 60/61/62/64Cu-ATSM: a hypoxia imaging agent for PET

Purpose Cu-diacetyl-bis(N⁴-methylthiosemicarbazone (Cu-ATSM) is an effective marker for the delineation of hypoxic tissue. Dosimetry calculations by the established Medical Internal Radionuclide Dose (MIRD) approach were performed with both animal and patient data.Methods Human absorbed dose estimates extrapolated from rat data were based on the biodistribution of ⁶¹Cu-ATSM in adult rats. Eighteen tissues were harvested and time–activity curves generated. The measured residence times and the MIRD S-values for ⁶⁰Cu-ATSM were used to estimate human absorbed doses. The biodistribution of the tracer was directly measured in five patients injected with approximately 480 MBq of ⁶⁰Cu-ATSM and imaged by positron emission tomography (PET) with a whole-body protocol. The combined data from all patients were used to derive organ residence times, and organ doses were calculated by MIRD methodology for ⁶⁰Cu-ATSM, ⁶¹Cu-ATSM, ⁶²Cu-ATSM, and ⁶⁴Cu-ATSM.Results Human absorbed dose estimates extrapolated from rat biodistribution data indicated that the kidneys appeared to be the dose-limiting organ (0.083 mGy/MBq) with a whole-body dose of 0.009 mGy/MBq. Based on the human PET imaging data, the liver appeared as the dose-limiting organ, with an average radiation dose of 0.064 mGy/MBq. The whole-body dose was 0.009 mGy/MBq and the effective dose was 0.011 mSv/MBq.Conclusion These relatively small absorbed doses to normal organs allow for the safe injection of 500–800 MBq of ⁶⁰Cu-ATSM, which is sufficient for PET imaging in clinical trials.     

Biodistribution and radiation dosimetry of [<Superscript>123</Superscript>I]ADAM in healthy human subjects: preliminary results

[(123)I]ADAM [2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM)] has recently been shown to be a very promising imaging ligand for the detection of serotonin transporters (SERT) in human brain, because of its high specificity for SERT. [(123)I]ADAM has previously been used only for animal studies. In this work, we investigated the radiation dosimetry and biodistribution of [(123)I]ADAM based on whole-body scans in healthy human volunteers. Following the administration of 196+/-20 MBq (range 157-220 MBq) [(123)I]ADAM, serial whole-body images were performed up to 24 h. Estimates of radiation absorbed dose were calculated using the MIRDOSE 3.0 program with a dynamic bladder model. Twelve source organs were considered in estimating absorbed radiation doses for organs of the body. The highest absorbed organ doses were found to the lower large intestine wall (8.3.10(-2) mGy/MBq), kidneys (5.2.10(-2) mGy/MBq), urinary bladder wall (4.9.10(-2) mGy/MBq) and thyroid (4.3.10(-2) mGy/MBq). The effective dose was estimated to be 2.2.10(-2) mSv/MBq. The results suggest that [(123)I]ADAM is of potential value as a tracer for single-photon emission tomography imaging of serotonin receptors in humans, with acceptable dosimetry and high brain uptake.     

PET-based human dosimetry of 18F-galacto-RGD, a new radiotracer for imaging alpha v beta3 expression.

(18)F-Galacto-RGD is a new tracer for PET imaging of alpha v beta3, a receptor involved in a variety of pathologic processes including angiogenesis and metastasis. Our aim was to study the dosimetry of (18)F-galacto-RGD in humans. METHODS: Eighteen patients with various tumors (musculoskeletal tumors [n = 10], melanoma [n = 5], breast cancer [n = 2], or head and neck cancer [n = 1]) were examined. After injection of 133-200 MBq of (18)F-galacto-RGD, 3 consecutive emission scans from the thorax to the pelvis were acquired at 6.7 +/- 2.9, 35.6 +/- 7.6, and 70.4 +/- 12.2 min after injection. Blood samples (n = 4) for metabolite analysis were taken 10, 30, and 120 min after injection. The OLINDA 1.0 program was used to estimate the absorbed radiation dose. RESULTS: Reversed-phase high-performance liquid chromatography of serum revealed that more than 95% of tracer was intact up to 120 min after injection. (18)F-Galacto-RGD showed rapid clearance from the blood pool and primarily renal excretion. Background activity in lung and muscle tissue was low (percentage injected dose per liter at 71 min after injection, 0.56 +/- 0.15 and 0.69 +/- 0.25, respectively). The calculated effective dose was 18.7 +/- 2.4 microSv/MBq, and the highest absorbed radiation dose was in the bladder wall (0.22 +/- 0.03 mGy/MBq). CONCLUSION: (18)F-Galacto-RGD demonstrates high metabolic stability, a favorable biodistribution, and a low radiation dose. Consequently, this tracer can safely be used for noninvasive imaging of molecular processes involving the alpha v beta3 integrin and for the planning and monitoring of therapeutic approaches targeting alpha v beta3.     

Biodistribution and radiation dosimetry of the amyloid imaging agent 11C-PIB in humans.

We investigated the biodistribution and radiation dosimetry of the PET amyloid imaging agent (11)C-PIB ((11)C-6-OH-BTA-1) (where BTA is benzothiazole) in humans. Previous radiation exposure estimates have been based on animal experiments. A dosimetry study in humans is essential for a balanced risk-benefit assessment of (11)C-PIB PET studies. METHODS: We used data from 16 different (11)C-PIB PET scans on healthy volunteers to estimate radiation exposure. Six of these scans were dynamic imaging over the abdominal region: 3 covering the upper abdomen and 3 covering the middle abdomen. On average, 489 MBq of (11)C-PIB (range, 416-606 MBq) were injected intravenously, and dynamic emission scans were recorded for up to 40 min. Two subjects had whole-body imaging over the entire body to illustrate the biodistribution. PET brain scans and blood and urine radioactivity measurements from our previous (11)C-PIB studies were also analyzed. Thirteen source organs and the remainder of the body were studied to estimate residence times and mean radiation-absorbed doses. The MIRD method was used to calculate the radiation exposure of selected target organs and the body as a whole. RESULTS: There is a high degree of consistency between our human data and previous biodistribution information based on baboons. In our study, the highest radiation-absorbed doses were received by the gallbladder wall (41.5 microGy/MBq), liver (19.0 microGy/MBq), urinary bladder wall (16.6 microGy/MBq), kidneys (12.6 microGy/MBq), and upper large intestine wall (9.0 microGy/MBq). The hepatobiliary and renal systems were the major routes of clearance and excretion, with approximately 20% of the injected radioactivity being excreted into urine. The effective radiation dose was 4.74 microSv/MBq. CONCLUSION: The established clinical dose of (11)C-PIB required for 3-dimensional PET amyloid imaging has an acceptable effective radiation dose. This dose is comparable with the average exposure expected in other PET brain receptor tracer studies. (11)C-PIB is rapidly cleared from the body, largely by the kidneys. From the viewpoint of radiation safety, these results support the use of (11)C-PIB in clinical PET studies.     

Estimation of absorbed dose for 2-[F-18]fluoro-2-deoxy-d- glucose using whole-body positron emission tomography and magnetic resonance imaging

The purpose of this study was to measure the cumulated activity and absorbed dose in organs after intravenous administration of 2-[F-18]fluoro-2-deoxy-d-glucose (¹⁸F-FDG) using whole-body positron emission tomography (PET) and magnetic resonance imaging (MRI). Whole-body dynamic emission scans for ¹⁸F-FDG were performed in six normal volunteers after transmission scans. The total activity of a source organ was obtained from the activity concentration of the organ measured by whole-body PET and the volume of that organ measured by whole-body T1-weighted MRI. The cumulated activity of each source organ was calculated from the time-activity curve. Absorbed doses to the individuals were estimated by the MIRD (medical internal radiation dosimetry) method using S-values adjusted to the individuals. Another calculation of cumulated activities and absorbed doses was performed using the organ volumes from the MIRD phantom and the ”Japanese reference man” to investigate the discrepancy of actual individual results against the phantom results. The cumulated activities of 18 source organs were calculated, and absorbed doses of 27 target organs estimated. Among the target organs, bladder wall, brain and kidney received the highest doses for the above three sets of organ volumes. Using measured individual organ volumes, the average absorbed doses for those organs were found to be 3.1×10^–1, 3.7×10^–2 and 2.8×10^–2 mGy/MBq, respectively. The mean effective doses in this study for individuals of average body weight (64.5 kg) and the MIRD phantom of 70 kg were the same, i.e. 2.9×10^–2 mSv/MBq, while for the Japanese reference man of 60 kg the effective dose was 2.1×10^–2 mSv/MBq. The results for measured organ volumes derived from MRI were comparable to those obtained for organ volumes from the MIRD phantom. Although this study considered ¹⁸F-FDG, combined use of whole-body PET and MRI might be quite effective for improving the accuracy of estimations of the cumulated activity and absorbed dose of positron-labelled radiopharmaceuticals. Received 23 October 1997 and in revised form 31 January 1998     

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.     

Human biodistribution and radiation dosimetry of the tachykinin NK1 antagonist radioligand [18F]SPA-RQ: comparison of thin-slice, bisected, and 2-dimensional planar image analysis.

(18)F-Labeled substance P antagonist-receptor quantifier ([(18)F]SPA-RQ) [2-fluoromethoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzyl]-[(2S,3S)-2-phenyl-piperidin-3-yl)amine] is a selective radioligand for in vivo quantification of tachykinin NK(1) receptors with PET. The aims of this study were to estimate the radiation safety profile and relative risks of [(18)F]SPA-RQ with 3 different methods of image analysis. METHODS: Whole-body PET images were acquired in 7 healthy subjects after injection of 192 +/- 7 MBq (5.2 +/- 0.2 mCi) [(18)F]SPA-RQ. Emission images were serially acquired at multiple time-points from 0 to 120 min and approximately 180-240 min after injection. Urine samples were collected after each imaging session and for 24 h after the last scan to measure excreted radioactivity. Horizontal tomographic images were compressed to varying degrees in the anteroposterior direction to create 3 datasets: thin-slice, bisected, and 2-dimensional (2D) planar images. Regions of interest were drawn around visually identifiable source organs to generate time-activity curves for each dataset. Residence times were determined from these curves, and doses to individual organs and the body as a whole were calculated using OLINDA/EXM 1.0. RESULTS: The lungs, upper large intestine wall, small intestine, urinary bladder wall, kidneys, and thyroid had the highest radiation-absorbed doses. Biexponential fitting of mean bladder and urine activity showed that about 41% of injected activity was excreted via urine. Assuming a 2.4-h urine voiding interval, the calculated effective doses from thin-slice, bisected, and 2D planar images were 29.5, 29.3, and 32.3 microSv/MBq (109, 108, and 120 mrem/mCi), respectively. CONCLUSION: Insofar as effective dose is an accurate measure of radiation risk, all 3 methods of analysis provided quite similar estimates of risk to human subjects. The radiation dose was moderate and would potentially allow subjects to receive multiple PET scans in a single year. Individual organ exposures varied among the 3 methods, especially for structures asymmetrically located in an anterior or posterior position. Bisected and 2D planar images almost always provided higher organ dose estimates than thin-slice images. Thus, either the bisected or 2D planar method of analysis appears acceptable for quantifying human radiation burden, at least for radioligands with a relatively broad distribution in the body and not concentrated in a small number of radiation sensitive organs.     

Dynamic evaluation of absorbed dose to the bladder wall with a balloon-bladder phantom during a study using [(18)F]fluorodeoxyglucose positron emission imaging

An accurate evaluation of the absorbed dose to the bladder wall from 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG) is clinically important because the bladder is considered as a critical organ in most positron emission tomography (PET) studies that cumulate about 20% of the total activity injection during image procedures. In the MIRD calculation, no allowance is made for the inclusion of all the dynamic parameters that affect the actual dose to the bladder wall to be taken in the dose assessment. The goal of the study is to propose a dose evaluation model by using a dynamic bladder phantom and time-activity curves from the bladder PET imaging. The proposed model takes all dynamic parameters into account and provides a much more accurate dose estimation to the bladder. In this study, the lowest dose to the bladder wall was obtained at the conditions of having a larger initial volume for the bladder contents and a higher production rate for urine. It is then advised patients to drink a bulk amount of water before the FDG injection or after urine voiding to facilitate urine production and to enlarge the bladder surface area, which are the most crucial steps in reducing the dose to the bladder wall. In our study, the voiding schedule in dose calculation plays certain roles although it is much more critical in the conventional MIRD calculation. The model estimated that the lowest dose to the bladder would occur at an initial void about 40 min after the FDG injection and the urine voiding was as complete as possible.     

Whole-body biodistribution and dosimetry estimates of a novel radiotracer for imaging of serotonin 4 receptors in brain: [18F]MNI-698

IntroductionA new radiotracer for imaging the serotonin 4 receptors (5-HT₄) in brain, [¹⁸F]MNI-698, was recently developed by our group. Evaluation in nonhuman primates indicates the novel radiotracer holds promise as an imaging agent of 5-HT₄ in brain. This paper aims to describe the whole-body biodistribution and dosimetry estimates of [¹⁸F]MNI-698.MethodsWhole-body positron emission tomography (PET) images were acquired over 240 minutes after intravenous bolus injection of [¹⁸F]MNI-698 in adult rhesus monkeys. Different models were investigated for quantification of radiation absorbed and effective doses using OLINDA/EXM 1.0 software.ResultsThe radiotracer main elimination route was found to be urinary and the critical organ was the urinary bladder. Modeling of the urinary bladder voiding interval had a considerable effect on the estimated effective dose. Normalization of rhesus monkeys’ organs and whole-body masses to human equivalent reduced the calculated dosimetry values. The effective dose ranged between 0.017 and 0.027 mSv/MBq.ConclusionThe dosimetry estimates, obtained when normalizing organ and whole-body weights and applying the urinary bladder model, indicate that the radiation doses from [¹⁸F]MNI-698 comply with limits and guidelines recommended by key regulatory authorities that govern the translation of radiotracers to human clinical trials. The timing of urinary bladder emptying should be considered when designing future clinical protocols with [¹⁸F]MNI-698, in order to minimize the subject absorbed doses.     

Human radiation dosimetry of [11C]MeAIB, a new tracer for imaging of system A amino acid transport

Purpose [N-methyl-¹¹C]α-methylaminoisobutyric acid ([¹¹C]MeAIB) is a promising positron emission tomography (PET) tracer for imaging hormonally regulated system A amino acid transport. Uptake of [¹¹C]MeAIB is totally specific for amino acid transport since [¹¹C]MeAIB is metabolically stable both extra- and intracellularly. The aim of this study was to measure cumulated radioactivity in different organs and estimate the absorbed radiation doses to humans with the Medical Internal Radiation Dosimetry (MIRD) method.Methods Radiation absorbed doses were calculated from PET images for 25 volunteers. Dynamic acquisition data were obtained for the thoracic, abdominal, femoral and head and neck regions. The median dose of intravenously injected [¹¹C]MeAIB was 422±35 MBq, with a range of 295–493 MBq. After PET imaging the radioactivity in voided urine was measured. Experimental human data were used for residence time estimates. Radiation doses were calculated with commonly used software.Results The effective dose for a 70-kg adult was 0.004 mSv/MBq, corresponding to a 1.72 mSv effective dose from the PET study with injection of 430 MBq [¹¹C]MeAIB. The highest absorbed doses were in the pancreas (0.018 mGy/MBq), kidneys (0.017 mGy/MBq), intestine (0.014 mGy/MBq), liver (0.008 mGy/MBq) and stomach (0.005 mGy/MBq). Only 0.57% of injected activity was excreted to urine within 1 h after injection.Conclusion Biodistribution of [¹¹C]MeAIB in the abdominal region reflected the high activity of the transportation of amino acids via system A and these organs also had the highest radiation doses. An effective dose of 0.004 mSv/MBq is fully justified when [¹¹C]MeAIB PET is performed to study system A activity in vivo.     

Whole-body distribution and dosimetry of O-(2-[18F]fluoroethyl)-L-tyrosine

The whole-body distribution of O-(2-[(18)F]fluoroethyl)- l-tyrosine (FET) was studied in seven patients with brain tumours by positron emission tomography (PET). Based on the IMEDOSE and MIRDOSE procedures, radiation absorbed doses were estimated from whole-body PET scans acquired approximately 70 and 200 min after i.v. injection of 400 MBq FET. After injection of FET, the peak of radioactivity in the blood was observed after 1.5 min, and a plateau of nearly constant radioactivity was reached at 20 min. The whole-body distribution of FET showed the highest activities in the urinary tract. All other organs exhibited only moderate FET uptake (SUV 相似文献   

Biodistribution and radiation dosimetry in healthy volunteers of a novel tumour-specific probe for PET/CT imaging: BAY 85-8050

Purpose

Novel tracers for the diagnosis of malignant disease with PET and PET/CT are being developed as the most commonly used ¹⁸F deoxyglucose (FDG) tracer shows certain limitations. Employing radioactively labelled glutamate derivatives for specific imaging of the truncated citrate cycle potentially allows more specific tumour imaging. Radiation dosimetry of the novel tracer BAY 85-8050, a glutamate derivative, was calculated and the effective dose (ED) was compared with that of FDG.

Methods

Five healthy volunteers were included in the study. Attenuation-corrected whole-body PET/CT scans were performed from 0 to 90 min, at 120 and at 240 min after injection of 305.0?±?17.6 MBq of BAY 85-8050. Organs with moderate to high uptake at any of the imaging time points were used as source organs. Total activity in each organ at each time point was measured. Time–activity curves (TAC) were determined for the whole body and all source organs. The resulting TACs were fitted to exponential equations and accumulated activities were determined. OLINDA/EXM software was used to calculate individual organ doses and the whole-body ED from the acquired data.

Results

Uptake of the tracer was highest in the kidneys due to renal excretion of the tracer, followed by the pancreas, heart wall and osteogenic cells. The mean organ doses were: kidneys 38.4?±?11.2 μSv/MBq, pancreas 23.2?±?3.8 μSv/MBq, heart wall 17.4?±?4.1 μSv/MBq, and osteogenic cells 13.6?±?3.5 μSv/MBq. The calculated ED was 8.9?±?1.5 μSv/MBq.

Conclusion

Based on the distribution and dose estimates, the calculated radiation dose of BAY 85-8050 is 2.67?±?0.45 mSv at a patient dose of 300 MBq, which compares favourably with the radiation dose of FDG (5.7 mSv).     

Biodistribution and radiation dosimetry of the dopamine D2 ligand 11C-raclopride determined from human whole-body PET.

Whole-body radiation dosimetry of 11C-raclopride was performed in healthy human volunteers. METHODS: Subjects (n = 6) were scanned with PET. Subjects received single-bolus injections of 11C-raclopride (S-(-)-3,5-dichloro-N-[(1-ethyl-2-pyrrolidinyl)]methyl-2-hydroxy-6-methoxybenzamide) (533 +/- 104 MBq) and were scanned for approximately 110 min with a 2-dimensional whole-body protocol. Regions of interest were placed over all visually identifiable organs and time-activity curves were generated. Residence times were computed as the area under the curve of the time-activity curves, normalized to injected activities and standard values of organ volumes. Absorbed doses were computed according to the MIRD schema with MIRDOSE3.1 software. RESULTS: Organs with the highest radiation burden were gallbladder wall, small intestine, liver, and urinary bladder wall. CONCLUSION: On the basis of the estimated absorbed dose, the maximum allowable single study dose under U.S. federal regulations for studies performed under Radiation Drug Research Committee is 1.58 GBq (42.8 mCi). This is still considerably higher than the doses of 11C-raclopride commonly used in research PET (370-555 MBq).