Biodistribution and radiation dosimetry of the dopamine transporter ligand.

18F-labeled 2 beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(-2-fluoroethyl)nortropane ([18F]FECNT) is a recently developed dopamine transporter ligand with potential applications in patients with Parkinson's disease and cocaine addiction. METHODS: Estimates of the effective dose equivalent and doses for specific organs were made using biodistribution data from 16 Sprague-Dawley rats and nine rhesus monkeys. PET images from two rhesus monkeys were used to calculate the residence time for the basal ganglia. The computer program MIRDOSE3 was used to calculate the dosimetry according to the methodology recommended by MIRD. RESULTS: The basal ganglia were the targeted tissues receiving the highest dose, 0.11 mGy/MBq (0.39 rad/mCi). The effective dose equivalent was 0.018 mSv/MBq (0.065 rem/mCi), and the effective dose was 0.016 mSv/MBq (0.058 rem/mCi). CONCLUSION: Our data show that a 185-MBq (5-mCi) injection of [18F]FECNT leads to an estimated effective dose of 3 mSv (0.3 rem) and an estimated dose to the target organ or tissue of 19.4 mGy (1.93 rad).     

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.     

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.     

Radiation dosimetry estimates of [18F]-fluoroacetate based on biodistribution data of rats

We estimated the dosimetry of [(18)F]fluoroacetate (FAC) with the method established by MIRD based on biodistribution data of rats. We selected some important organs and computed their residence time, their absorbed doses and effective dose with the (%ID(Organ)) (human) data using OLINDA/EXM 1.1 program. We observed the highest absorbed doses in the heart wall (0.025mGy/MBq) and the lowest in skin (0.0079mGy/MBq). The total mean absorbed doses and the effective doses were 0.011mGy/MBq and 0.014mSv/MBq, respectively. A 370-MBq injection of FAC leads to an estimated effective dose of 5.2mSv. The potential radiation risk associated with FAC/PET imaging is well within the accepted limits.     

Radiation dosimetry of <Emphasis Type="Italic">N</Emphasis>-([<Superscript>11</Superscript>C]methyl)benperidol as determined by whole-body PET imaging of primates

Purpose N-([¹¹C]methyl)benperidol ([¹¹C]NMB) can be used for positron emission tomography (PET) measurements of D₂-like dopamine receptor binding in vivo. We report the absorbed radiation dosimetry of i.v.-administered ¹¹C-NMB, a critical step before applying this radioligand to imaging studies in humans. Materials and methods Whole-body PET imaging with a CTI/Siemens ECAT 953B scanner was done in a male and a female baboon. After i.v. injection of 444–1221 MBq of ¹¹C-NMB, sequential images taken from the head to the pelvis were collected for 3 h. Volumes of interest (VOIs) were identified that entirely encompassed small organs (whole brain, striatum, eyes, and myocardium). Large organs (liver, lungs, kidneys, lower large intestine, and urinary bladder) were sampled by drawing representative regions within the organ volume. Time–activity curves for each VOI were extracted from the PET, and organ residence times were calculated by analytical integration of a multi-exponential fit of the time–activity curves. Human radiation doses were estimated using OLINDA/EXM 1.0 and the standard human model. Results Highest retention was observed in the blood and liver, each with total residence times of 1.5 min. The highest absorbed radiation doses were to the heart (10.5 mGy/kBq) and kidney (9.19 mGy/kBq), making these the critical organs for [¹¹C]NMB. A heart absorption of 50 mGy would result from an injected dose of 4,762 MBq [¹¹C]NMB. Conclusions Thus, this study suggests that up to 4,762 MBq of [¹¹C]NMB can be safely administered to human subjects for PET studies. Total body dose and effective dose for [¹¹C]NMB are 2.82 mGy/kBq and 3.7 mSv/kBq, respectively.     

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.     

Biodistribution and radiation dosimetry of [N-methyl-11C]mirtazapine, an antidepressant affecting adrenoceptors.

Central adrenoceptors cannot currently be studied by PET neuroimaging due to a lack of appropriate radioligands. The fast-acting antidepressant drug mirtazapine, radiolabelled for PET, may be of value for assessing central adrenoceptors, provided that the radiation dosimetry of the radioligand is acceptable. To obtain that information, serial whole-body images were made for up to 70 min following intravenous injection of 326 and 185 MBq [N-methyl-11C]mirtazapine (specific activities E.O.S. of 119 and 39G Bq/micromol, respectively) in a healthy volunteer. Ten source organs plus remaining body were considered in estimating absorbed radiation doses calculated using MIRD 3.1. The highest absorbed organ doses were found to the lungs (3.4 x 10(-2) mGy/MBq), adrenals (1.2 x 10(-2) mGy/MBq), spleen (1.2 x 10(-2) mGy/MBq), and gallbladder wall (1.1 x 10(-2) mGy/MBq). The effective dose was estimated to be 6.8 x 10(-3) mSv/MBq, which is similar to that produced by several radioligands used routinely for neuroimaging.     

Pharmacokinetics and radiation dosimetry estimation of O-(2-[18F]fluoroethyl)-L-tyrosine as oncologic PET tracer.

An easy-to-automate synthetic procedure and the kinetics and radiation dosimetry of O-(2-[18F]fluoroethyl)-L-tyrosine (FET), a recently developed amino acid tracer with potential applications in tumor imaging with PET, are described. FET was prepared in high radiochemical yield, 20-25% with no decay correction, and radiochemical purity of more than 95% in less than 60min synthesis time by a modified two-step procedure and manual operation. The kinetics and radiation dosimetry of FET were evaluated by using mice biodistribution data and the medical internal radiation dosimetry (MIRD) method. The bone (total) was the organ receiving the highest dose, 4.78x10(-3)mGy/MBq, and the brain and the whole body received the lowest dose, 1.6x10(-3)mGy/MBq, respectively. The effective dose was 9.0x10(-3)mSv/MBq. The data show that a 370-MBq (10mCi) injection of FET leads to an estimated effective dose of 3.3mSv and an estimated dose to the whole body of 0.6mGy. The potential radiation risks associated with this study are well within accepted limits.     

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.     

Radiation dosimetry of a 99mTc-labeled IgM murine antibody to CD15 antigens on human granulocytes.

99mTc-labeled anti-stage specific embryonic antigen-1 (anti-SSEA-1) is an injectable IgM antibody derived from mice. It binds to CD15 antigens on some granulocytic subpopulations of human white blood cells in vivo after systemic administration. The purpose of this study was to measure biodistribution of 99mTc-labeled anti-SSEA-1 and perform radiation dosimetry in 10 healthy human volunteers. METHODS: Transmission scans and whole-body images were acquired sequentially on a dual-head camera for 32 h after the intravenous administration of about 370 MBq (10.0 mCi) of the radiopharmaceutical. Renal excretion fractions were measured from 10 to 14 discrete urine specimens voided over 27.9 +/- 2.0 h. Multiexponential functions were fit iteratively to the time-activity curves for 17 regions of interest using a nonlinear least squares regression algorithm. The curves were integrated numerically to yield source organ residence times. Gender-specific radiation doses were then estimated individually for each subject, using the MIRD technique, before any results were averaged. RESULTS: Quantification showed that the kidneys excreted 39.5% +/- 6.5% of the administered dose during the first 24 h after administration. Image analysis showed that 10%-14% of the radioactivity went to the spleen, while more than 40% went to the liver. Residence times were longest in the liver (3.37 h), followed by the bone marrow (1.09 h), kidneys (0.84 h) and the spleen (0.65 h). The dose-limiting organ in both men and women was the spleen, which received an average of 0.062 mGy/MBq (0.23 rad/mCi, range 0.08-0.30 rad/mCi), followed by the kidneys (0.051 mGy/MBq), liver (0.048 mGy/MBq) and urinary bladder (0.032 mGy/MBq). The effective dose equivalent was 0.018 mSv/MBq (0.068 rem/mCi). CONCLUSION: The findings suggest that the radiation dosimetry profile for this new infection imaging agent is highly favorable.     

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.     

Dosimetry of the dopamine transporter radioligand 18F-FPCIT in human subjects.

This study was designed to evaluate the radiation dosimetry in human subjects for a new radiopharmaceutical, N-(3-(18)F-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane ((18)F-FPCIT). The goal was to determine a limiting dose consistent with accepted guidelines for use in clinical studies and to compare the radiation burden with other agents such as (123)I-FPCIT, (18)F-fluorodopa, and (18)F-FDG. METHODS: Dynamic PET scans of the urinary bladder were obtained in 6 subjects; 2 subjects had brain scans and 5 subjects had scans of the thorax or abdomen. Regions of interest were placed over composite images of each organ for which activity was visualized to generate time-activity curves. Doses were calculated from residence times using the MIRDOSE3 program. RESULTS: The critical organ for dosimetry is the urinary bladder wall with a dose of 0.0586 +/- 0.0164 mGy/MBq. The dose comes primarily (97.2%) from activity in the urinary bladder contents. The dose is lower than any of the other agents used commonly in PET to assess dopaminergic function. The effective dose equivalent (0.0120 mGy/MBq) is also lower than comparable compounds. CONCLUSION: (18)F-FPCIT has favorable dosimetry when compared with other agents used to study dopaminergic function. Doses as high as 853 MBq (23 mCi) may be given to adult patients and remain within accepted guidelines.     

Biodistribution, radiation dose estimates, and in vivo Pgp modulation studies of 18F-paclitaxel in nonhuman primates.

Multidrug resistance (MDR) associated with increased expression and function of the P-glycoprotein (Pgp) efflux pump often causes chemotherapeutic failure in cancer. To provide insight into both the dynamics of the pump and the effects of MDR, we radiolabeled paclitaxel, a substrate for the Pgp pump, with (18)F to study MDR in vivo with PET. We obtained biodistribution and radiation dose estimates for (18)F-paclitaxel (FPAC) in monkeys and studied the effects of a Pgp blocker (XR9576, tariquidar) on FPAC kinetics. METHODS: Paired baseline and Pgp modulation (2 mg/kg XR9576) 4-h whole-body dynamic PET scans were obtained in 3 rhesus monkeys after injection of FPAC. Measured residence times were extrapolated to humans and radiation dose estimates were obtained using MIRDOSE3.1. The postmodulator area under the time-activity curves (AUCs) and Logan plot slopes, a measure of tracer distribution volume (equilibrium tissue-to-plasma ratio) that is inversely proportional to tracer efflux, were compared with baseline values to determine changes in FPAC distribution. RESULTS: Cumulative activities of the organs sampled accounted for 80% of the injected dose. The critical organ is gallbladder wall (0.19 mGy/MBq [0.69 rad/mCi]), followed by liver (0.14 mGy/MBq [0.52 rad/mCi]); the effective dose is 0.022 mSv/MBq (0.083 rem/mCi). XR9576 preinfusion changed the Logan plot slope for liver by +104% (P = 0.02), lung by +87% (P = 0.11), and kidney by -14% (P = 0.08). Changes in the mean AUC (normalized to the plasma AUC) were +54% (P = 0.08), +97% (P = 0.04), and -12% (P = 0.02), respectively, for liver, lung, and kidney. No significant difference was found in the metabolite-corrected plasma AUC (normalized to the injected dose) between the baseline and XR9576 modulator studies (P = 0.69). CONCLUSION: Under Radioactive Drug Research Committee guidelines, 266 MBq (7.2 mCi) FPAC can be administered to humans up to 3 times a year. The increase in FPAC accumulation in liver and lung after XR9576 is consistent with Pgp inhibition and demonstrates the potential of FPAC to evaluate MDR.     

Preclinical acute toxicity studies and rodent-based dosimetry estimates of the novel sigma-1 receptor radiotracer [(18)F]FPS

[(18)F]1-(Fluoropropyl)-4-[(4-cyanophenoxy)methyl]piperidine ([(18)F]FPS) is a novel high affinity (KD = 0.5 nM) sigma receptor radioligand that exhibits saturable and selective in vivo binding to sigma receptors in rats, mice and non-human primates. In order to support an IND application for the characterization of [(18)F]FPS through PET imaging studies in humans, single organ and whole body radiation adsorbed doses associated with [(18)F]FPS injection were estimated from distribution data obtained in rats. In addition, acute toxicity studies were conducted in rats and rabbits and limited toxicity analyses were performed in dogs. Radiation dosimetry estimates obtained using rat biodistribution analysis of [(18)F]FPS suggest that most organs would receive around 0.012-0.015 mGy/MBq. The adrenal glands, brain, kidneys, lungs, and spleen would receive slightly higher doses (0.02-0.03 mGy/MBq). The adrenal glands were identified as the organs receiving the greatest adsorbed radiation dose. The total exposure resulting from a 5 mCi administration of [(18)F]FPS is well below the FDA defined limits for yearly cumulative and per study exposures to research participants. Extended acute toxicity studies in rats and rabbits, and limited acute toxicity studies in beagle dogs suggest at least a 175-fold safety margin in humans at a mass dose limit of 2.8 microg per intravenous injection. This estimate is based on the measured no observable effect doses (in mg/m(2)) in these species. These data support the expectation that [(18)F]FPS will be safe for use in human PET imaging studies at a maximum administration of 5 mCi and a mass dose equal to or less than 2.8 microg FPS per injection.     

Primary lung cancer: biodistribution and dosimetry of two In-111- labeled monoclonal antibodies

This study was undertaken to measure the biokinetics and organ dosimetry of indium-111-labeled monoclonal antibodies (MoAbs) with a whole-body gamma camera imaging technique. Twenty patients with primary lung cancer were studied with two different MoAb agents (anti-carcinoembryonic antigen ZCEO25 and antiadenocarcinoma LA20207). Imaging was performed at 1, 24, 72, and 144 hours after injection. Scintigraphic whole-body retention was verified by means of comparison with the results from in vitro counting of excreta. Organ retention was verified in an abdominal phantom. The MoAb cleared slowly from the heart and lungs, the brain and spleen showed no clearance, and the liver showed increased activity over the 6-day period. Dosimetry for ZCE025 showed a dose to the liver of 1.3 rad/mCi (0.36 mGy/MBq); heart, 1.5 rad/mCi (0.40 mGy/MBq); spleen, 1.1 rad/mCi (0.29 mGy/MBq); total body, 0.49 rad/mCi (0.13 mGy/MBq); and testes, 0.39 rad/mCi (0.11 mGy/MBq). The dosimetry for LA20207 was similar.     

Biodistribution and radiation dosimetry of the norepinephrine transporter radioligand (<Emphasis Type="Italic">S</Emphasis>,<Emphasis Type="Italic">S</Emphasis>)-[<Superscript>18</Superscript>F]FMeNER-D<Subscript>2</Subscript>: a human whole-body PET study

Purpose (S,S)-[¹⁸F]FMeNER-D₂ is a recently developed positron-emission tomography (PET) radioligand for in vivo quantification of the norepinephrine transporter system. The aim of this study was to provide dosimetry estimates for (S,S)-[¹⁸F]FMeNER-D₂ based on human whole-body PET measurements. Methods PET scans were performed for a total of 6.4 h after the injection of 168.9 ± 31.5 MBq of (S,S)-[¹⁸F]FMeNER-D₂ in four healthy male subjects. Volumes of interest were drawn on the coronal images. Estimates of the absorbed dose of radiation were calculated using the OLINDA software. Results Uptake was largest in lungs, followed by liver, bladder, brain and other organs. Peak values of the percent injected dose (%ID) at a time after radioligand injection were calculated for the lung (21.6%ID at 0.3 h), liver (5.1%ID at 0.3 h), bladder (12.2%ID at 6 h) and brain (2.3%ID at 0.3 h). The largest absorbed dose was found in the urinary bladder wall (0.039 mGy/MBq). The calculated effective dose was 0.017 mSv/MBq. Conclusion Based on the distribution and dose estimates, the estimated radiation burden of (S,S)-[¹⁸F]FMeNER-D₂ is lower than that of [¹⁸F]FDG. The radioligand would allow multiple PET examinations in the same research subject per year.     

Radiosynthesis of [F] N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophenyl) nortropane and the first human study with positron emission tomography

A procedure for the routine preparation of [¹⁸F]FP-CIT has been developed. Purification of the final product was achieved by preparative HPLC using phenethyl column without decomposition or epimerization. [¹⁸F] labeled-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane was prepared and PET imaging was performed on human subjects. A high uptake into striatal regions was observed. HPLC plasma analysis using [¹⁸F]FP-CIT indicated the presence of only one metabolite. By directly comparing the behavior of these three radiotracers ([¹⁸F]DOPA, [¹²³I]FP-CIT, and [¹⁸F]FP-CIT) in the same subjects, we can enhance our understanding of the dopaminergic system as well as the relative potential of these techniques in a clinical research setting.     

Equilibrium modeling of 5-HT(2A) receptors with [18F]deuteroaltanserin and PET: feasibility of a constant infusion paradigm

ABSTRACT. [¹⁸F]Altanserin has emerged as a promising positron emission tomography (PET) ligand for serotonin-2A (5-HT_2A) receptors. The deuterium substitution of both of the 2′-hydrogens of altanserin ([¹⁸F]deuteroaltanserin) yields a metabolically more stable radiotracer with higher ratios of parent tracer to radiometabolites and increased specific brain uptake than [¹⁸F]altanserin. The slower metabolism of the deuterated analog might preclude the possibility of achieving stable plasma and brain activities with a bolus plus constant infusion within a reasonable time frame for an ¹⁸F-labeled tracer (T_1/2 110 min). Thus, the purpose of this study was to test the feasibility in human subjects of a constant infusion paradigm for equilibrium modeling of [¹⁸F]deuteroaltanserin with PET. Seven healthy male subjects were injected with [¹⁸F]deuteroaltanserin as a bolus plus constant infusion lasting 10 h postinjection. PET acquisitions and venous blood sampling were performed throughout the infusion period. Linear regression analysis revealed that time-activity curves for both specific brain uptake and plasma [¹⁸F]deuteroaltanserin concentration stabilized after about 5 h. This permitted equilibrium modeling and estimation of V^′₃ (ratio of specific uptake to total plasma parent concentration) and the binding potential V₃ (ratio of specific uptake to free plasma parent concentration). Cortical/cerebellar ratios were increased by 26% relative to those we previously observed with [¹⁸F]altanserin using similar methodology in a somewhat older subject sample. These results demonstrate feasibility of equilibrium imaging with [¹⁸F]deuteroaltanserin and suggest that it may be superior to [¹⁸F]altanserin as a PET radioligand.     

Lacrimal gland dosimetry for the brain imaging agent technetium-99m-HMPAO

We calculated lacrimal gland dosimetry for the brain imaging agent 99mTc-HMPAO. One hundred thirty-eight patients were studied using a dedicated brain imaging device. Only 11% of the patients showed lacrimal gland uptake. For a 740-MBq (20 mCi) injected dose of 99mTc-HMPAO, the radiation exposure to the lacrimal glands is 10.2 mGy (1.02 rad), or 0.0138 mGy/MBq (0.051 rad/mCi). These values are five times lower than the ones reported by the manufacturer of HMPAO. As the dosimetry calculation is only for subjects showing 99mTc-HMPAO uptake in the lacrimal gland, the average radiation dose to all subjects is considerably lower, 1/10 of the estimated value.