Nuclear Medicine and Biology

Editorial Board

2012-02-01

Synthesis and evaluation of [18F]exendin (9–39) as a potential biomarker to measure pancreatic β-cell mass

2011-10-28

Abstract: Introduction: Glucagon-like peptide 1 (GLP-1) is released in response to food intake and plays an important role in maintaining blood glucose homeostasis. Exendin (9–39), a potent glucagon-like peptide 1 receptor antagonist, has been labeled with In-111 for SPECT imaging. We report here the first radiosynthesis of [18F]exendin (9–39) ([18F]Ex(9–39)) and an evaluation of its potential as a biomarker for in vivo positron emission tomography (PET) imaging of pancreatic β-cell mass (BCM) in rats.Methods: F-18 label was introduced by conjugation of [18F]4-fluorobenzaldehyde with an Ex(9–39) derivative containing a 6-hydrazinonicotinyl group on the ɛ-amine of Lys27. Positron emission tomography imaging was carried out in Sprague–Dawley rats (five control and five streptozotocin-induced diabetic) and BioBreeding diabetes-prone rats (three at 7 weeks and three at 12 weeks) using the high-resolution research tomograph (HRRT) after 0.187±0.084 mCi [18F]Ex(9–39) administration. Time–activity curves were obtained from pancreas, liver and kidney. Pancreases were assayed for insulin content after the imaging study.Results: Site-specifically labeled [18F]Ex(9–39) was purified on a G15 open column with radiochemical and chemical purities >98%. Positron emission tomography imaging showed pancreatic standardized uptake value (SUV) peaked at 10 min and plateaued by 50 min to the end of scan (240 min). No correlations of pancreatic SUV with postmortem measures of insulin content were seen.Conclusions: [18F]Ex(9–39) was successfully prepared and used for PET imaging for the first time to measure pancreatic BCM. The results suggest that derivatization of the Lys27 residue might reduce binding affinity, as evidenced by the absence of specific binding. Exendin analogues radiolabeled at other sites may elucidate the active site required for binding.

Radiolabeled Cu-ATSM as a novel indicator of overreduced intracellular state due to mitochondrial dysfunction: studies with mitochondrial DNA-less ρ0 cells and cybrids carrying MELAS mitochondrial DNA mutation

2011-10-28

Abstract: Objectives: Radiolabeled Cu-diacetyl-bis (N4-methylthiosemicarbazone) (⁎Cu-ATSM), including 60/62/64Cu-ATSM, is a potential imaging agent of hypoxic tumors for positron emission tomography (PET). We have reported that ⁎Cu-ATSM is trapped in tumor cells under intracellular overreduced states, e.g., hypoxia. Here we evaluated ⁎Cu-ATSM as an indicator of intracellular overreduced states in mitochondrial disorders using cell lines with mitochondrial dysfunction.Methods: Mitochondrial DNA-less ρ0206 cells; the parental 143B human osteosarcoma cells; the cybrids carrying mutated mitochondria from a patient of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) (2SD); and that carrying wild-type one (2SA) were used. Cells were treated under normoxia or hypoxia, and 64Cu-ATSM uptake was examined to compare it with levels of biological reductant NADH and NADPH.Results: ρ0206 cells showed higher 64Cu-ATSM uptake than control 143B cells under normoxia, whereas 64Cu-ATSM uptake was not significantly increased under hypoxia in ρ0206 cells. Additionally, 64Cu-ATSM uptake showed correlate change to the NADH and NADPH levels, but not oxygenic conditions. 2SD cells showed increased 64Cu-ATSM uptake under normoxia as compared with the control 2SA, and 64Cu-ATSM uptake followed NADH and NADPH levels, but not oxygenic conditions.Conclusions: 64Cu-ATSM accumulated in cells with overreduced states due to mitochondrial dysfunction, even under normoxia. We recently reported that 62Cu-ATSM-PET can visualize stroke-like episodes maintaining oxygen supply in MELAS patients. Taken together, our data indicate that ⁎Cu-ATSM uptake reflects overreduced intracellular states, despite oxygenic conditions; thus, ⁎Cu-ATSM would be a promising marker of intracellular overreduced states for disorders with mitochondrial dysfunction, such as MELAS, Parkinson's disease and Alzheimer's disease.

Evaluation of copper-64-labeled somatostatin agonists and antagonist in SSTr2-transfected cell lines that are positive and negative for p53: implications for cancer therapy

Kim Nguyen, Jesse J. Parry, Buck E. Rogers, Carolyn J. Anderson — 2011-11-07

Abstract: Objectives: Radiolabeled somatostatin analogs have become important agents for molecular imaging and targeted radiotherapy of somatostatin receptor-positive tumors. Here we determine the effect of the tumor suppressor protein, p53, on trafficking 64Cu to tumor cell nuclei from DOTA vs. CB-TE2A-conjugated agonist Y3-TATE and the antagonist 64Cu-CB-TE2A-sst2-ANT in cell lines that are positive or negative for p53.Methods: Receptor binding, internalization, cyclic adenosine monophosphate (cAMP) and nuclear localization studies were performed with the somatostatin receptor subtype 2 (SSTr2) agonists, 64Cu-CB-TE2A-Y3-TATE and 64Cu-DOTA-Y3-TATE vs. antagonist, 64Cu-CB-TE2A-sst2-ANT, in SSTr2-transfected p53 +/+ and −/− HCT116 colorectal carcinoma cells.Results: The antagonist, 64Cu-CB-TE2A-sst2-ANT, bound 8–9-fold more SSTr2 binding sites than did the 64Cu-labeled agonists. 64Cu-CB-TE2A-Y3-TATE was more efficiently internalized than 64Cu-DOTA-Y3-TATE, while 64Cu-CB-TE2A-sst2-ANT showed lower yet significant levels of internalization. CB-TE2A-Y3-TATE acted as a full agonist, inhibiting cAMP production, whereas CB-TE2A-sst2-ANT showed no inhibition of cAMP production. The 64Cu from agonists 64Cu-DOTA-Y3-TATE and 64Cu-CB-TE2A-Y3-TATE showed greater nuclear localization at 24 h in p53 +/+ vs. −/− cells; however, there was no difference in the levels of 64Cu from the antagonist based on p53 status. Surprisingly, the DOTA and CB-TE2A-conjugated agonists showed similar nuclear localization in the p53 +/+ and −/− cells, suggesting no difference in 64Cu release from these chelators in the HCT116 cell lines.Conclusion: Based on these in vitro data, the agonist 64Cu-CB-TE2A-Y3-TATE demonstrates the most promise as an agent for targeted radiotherapy in p53 positive, SSTr2-positive tumors.

PET study using [11C]FTIMD with ultra-high specific activity to evaluate I2-imidazoline receptors binding in rat brains

2011-09-28

Abstract: Introduction: We recently developed a selective 11C-labeled I2-imidazoline receptor (I2R) ligand, 2-(3-fluoro-4-[11C]tolyl)-4,5-dihydro-1H-imidazole ([11C]FTIMD). [11C]FTIMD showed specific binding to I2Rs in rat brains having a high density of I2R, as well as to I2Rs those in monkey brains, as illustrated by positron emission tomography (PET) and autoradiography. However, [11C]FTIMD also showed moderate non-specific binding in rat brains. In order to increase the specificity for I2R in rat brains, we synthesized [11C]FTIMD with ultra-high specific activity and evaluated its binding.Methods: [11C]FTIMD with ultra-high specific activity was prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [11C]methyl iodide, which was produced by iodination of [11C]methane using the single-pass method. Dynamic PET scans were conducted in rats, and the kinetic parameters were estimated.Results: [11C]FTIMD with ultra-high specific activity was successfully synthesized with an appropriate level of radioactivity and ultra-high specific activity (4470±1660 GBq/μmol at end of synthesis, n=11) for injection. In the PET study, distribution volume (VT) values in all the brain regions investigated whether I2R expression was greatly reduced in BU224-pretreatead rats compared with control rats (29–45% decrease). Differences in VT values between control and BU224-pretreated rats using [11C]FTIMD with ultra-high specific activity were greater than those using [11C]FTIMD with normal specific activity (17–34% decrease) in all brain regions investigated.Conclusion: Quantitative PET using [11C]FTIMD with ultra-high specific activity can contribute to the detection of small changes in I2R expression in the brain.

Studies of the myocardial uptake and excretion mechanisms of a novel 99mTc heart perfusion agent

Filipa Mendes, Lurdes Gano, Célia Fernandes, António Paulo, Isabel Santos — 2011-11-14

Abstract: Introduction: 99mTc-TMEOP is a novel heart perfusion radiotracer exhibiting high initial and persistent heart uptake associated with rapid blood and liver clearance. This study aimed at determining the mechanisms of myocardial localization and fast liver clearance of 99mTc-TMEOP.Methods: Subcellular distribution of 99mTc-TMEOP was determined in excised rat heart tissue by differential centrifugation. The effect of cyclosporin A on the pharmacokinetic behaviour of 99mTc-TMEOP was evaluated by both ex vivo biodistribution and in vivo planar imaging studies.Results: Subcellular distribution studies showed that more than 73% of 99mTc-TMEOP was associated with the mitochondrial fraction. Comparison with subcellular distribution of 99mTc-sestamibi showed no significant difference in the mitochondrial accumulation between the two tracers. Biodistribution studies in the presence of cyclosporin A revealed an increase in kidneys and liver uptake of 99mTc-TMEOP, suggesting the involvement of multidrug resistance transporters in determining its pharmacokinetic profile.Conclusions: The heart uptake mechanism of 99mTc-TMEOP is similar to that of the other reported monocationic 99mTc cardiac agents and is associated with its accumulation in the mitochondria. Cyclosporin A studies indicate that the fast liver and kidney clearance kinetics is mediated by P-glycoprotein (Pgp), supporting the potential interest of this radiotracer for imaging Pgp function associated with multidrug-resistant tumours.

Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma

2011-09-28

Abstract: Purpose: To evaluate the usefulness of [18F]-6-fluorodopamine ([18F]-DA) and [18F]-L-6-fluoro-3,4-dihydroxyphenylalanine ([18F]-DOPA) positron emission tomography (PET) in the detection of subcutaneous (s.c.) and metastatic pheochromocytoma in mice; to assess the expression of the norepinephrine transporter (NET) and vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2), all important for [18F]-DA and [18F]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse.Methods: SUVmax values were calculated from [18F]-DA and [18F]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated.Results: [18F]-DA detected less metastatic lesions compared to [18F]-DOPA. TLR values for liver metastases were 2.26–2.71 for [18F]-DOPA and 1.83–2.83 for [18F]-DA. A limited uptake of [18F]-DA was found in s.c. tumors (TLR=0.22-0.27) compared to [18F]-DOPA (TLR=1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c. tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [18F]-DA's high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage and retention in pheochromocytoma cell vesicles. In contrast, [18F]-DOPA was found to utilize only VMAT2.Conclusion: MRI was superior in the detection of all organ tumors compared to microCT and PET. [18F]-DOPA had overall better sensitivity than [18F]-DA for the detection of metastases. Subcutaneous tumors were localized only with [18F]-DOPA, a finding that may reflect differences in expression of VMAT1 and VMAT2, perhaps similar to some patients with pheochromocytoma where [18F]-DOPA provides better visualization of lesions than [18F]-DA.

Difficulties in dopamine transporter radioligand PET analysis: the example of LBT-999 using [18F] and [11C] labelling: Part I: PET studies

2011-10-28

Abstract: Background: LBT-999 (E)-N-(4-fluorobut-2-enyl)-2β-carbomethoxy-3β-(4′-tolyl)nortropane is a dopamine transporter (DAT) ligand. [18F]LBT-999 was first labelled with carbon-11; we will now describe its in vivo behaviour in comparison to that of [11C]LBT-999.Methods/Results: Positron emission tomography (PET) experiments (baboons) confirmed the high affinity/specificity of [18F]LBT-999 for DAT. The brain regional distribution was in accordance with that of DAT. Pre-treatment with LBT-999 (1 mg/kg iv), but not with desipramine, a norepinephrine (NET) antagonist, reduced the striatum-to-cerebellum ratio by 96%, confirming the specificity for DAT vs. NET. The parent compound decreased rapidly and represented 24.3±5.0% of plasma radioactivity at 30 min pi. Whole-body scans showed an important bone uptake of free fluorine following metabolism of [18F]LBT-999. In the cerebellum and striatum, distribution volumes increased by 30–40% between 80 and 230 min, suggesting the polluting role of a radiometabolite(s). [11C]LBT-999 exhibited a 40% higher standardized uptake value in the striata. This difference is likely due to N-dealkylation followed by [18F]fluoride release. 2β-Carbomethoxy-3β-(4′-tolyl) nortropane is then formed, while [11C]2β-carbomethoxy-3β-(4′-tolyl) nortropane is formed following injection of [11C]LBT-999. This metabolite has high affinity for the DAT. In one specific PET experiment, intravenous injection of this metabolite induced a strong displacement of [18F]LBT-999 in the striata, confirming that this metabolite readily crosses the blood–brain barrier (BBB) and binds to DAT.Conclusions: [18F]LBT-999 is N-dealkylated in vivo to yield (1) a nonradioactive metabolite that crosses the BBB and has a high affinity for the DAT and (2) a [18F]fluoro-alkyl chain which is further defluorinated. The temporal changes in distribution volumes are consistent with the accumulation of a radiometabolite(s) in the brain. Therefore, the quantification of DAT density with [18F]LBT-999 is rather difficult.

Synthesis and evaluation of a C-6 alkylated pyrimidine derivative for the in vivo imaging of HSV1-TK gene expression

2011-09-28

Abstract: Introduction: We report on the synthesis, radiolabeling, in vitro and in vivo characterization of N-Me-[18F]FHBT (6-(3-[18F]fluoro-2-(hydroxymethyl)propyl)-1,5-dimethylpyrimidin-2,4(1H,3H)-dione), a C-6-substituted N-1-methylated pyrimidine derivative as a reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-TK) expression.Methods: N-Me-[18F]FHBT was synthesized via a standard nucleophilic substitution reaction followed by acidic cleavage of the methoxytrityl protecting group. Cell uptake was studied in vitro with control HEK293 (human embryonic kidney cells) and HEK293 cells stably transfected with nonmutant HSV1-tk (HEK293TK+ cells). Positron emission tomography (PET) imaging and biodistribution studies of N-Me-[18F]FHBT or [18F]FHBG were performed in nude mice bearing xenografts of HEK293 control and TK+ cells.Results: N-Me-[18F]FHBT was obtained in a two-step reaction in an overall maximal radiochemical yield (decay-corrected) of 5% and a radiochemical purity >96%. The tracer uptake in HSV1-TK containing HEK293TK+ cells was 14.5 times (at 30 min) and 55.4 times (at 240 min) higher than in control HEK293 cells. In mice, N-Me-[18F]FHBT and [18F]FHBG accumulated significantly and exhibited similar radioactivity levels in the HEK293TK+ xenografts; however, standardized uptake values ratios between HEK293TK+ and HEK293 control xenografts were higher for [18F]FHBG than for N-Me-[18F]FHBT. Both tracers showed high gall bladder and abdominal activity.Conclusion: The biological evaluations demonstrated the feasibility of using N-methylated C-6-substituted pyrimidine derivative N-Me-[18F]FHBT as a PET radiotracer for monitoring HSV1-TK expression in vivo.

Radiohalogenated 4-anilinoquinazoline-based EGFR-TK inhibitors as potential cancer imaging agents

2011-11-14

Abstract: Introduction: The overexpression of epidermal growth factor receptor (EGFR) in tumors underlines the recent interest in EGFR as attractive target for the development of new cancer imaging agents. EGFR-tyrosine kinase inhibitors (EGFR-TKIs) based on the anilinoquinazoline scaffold have been explored as potential probes for EGFR imaging. However, up to now, no optimal radiotracer is available. Herein, we report the synthesis and biological evaluation of three novel halogenated 6-substituted 4-anilinoquinazoline based EGFR-TKIs. Radiosynthesis (125I and 18F) of the corresponding analogues was also performed.Methods: 6a, 6b and 8 were obtained by reaction of 6-amino-4-anilinoquinazoline (5) with 3-/4-iodobenzoyl and 4-fluorobenzoyl chlorides. Inhibition of EGFR autophosphorylation and A431 cellular proliferation were assessed by Western blot and MTT assays. 125I-anilinoquinazolines [125I]6a/b were prepared via destannylation of the corresponding tributylstannyl precursors with [125I]NaI. Cellular uptake studies were conducted in A431 cells. Optimization of the radiosynthesis of the 18F-anilinoquinazoline [18F]8 was attempted by nucleophilic substitution of the trimethylammonium- and nitro-6-substituted 4-anilinoquinazoline precursors.Results: 6a, 6b and 8 were synthesized in high chemical yield. All of them are inhibitors of EGFR autophosphorylation (0.1

Nonlinear compartmental model of 18F-choline

2011-12-02

Abstract: Introduction: This work develops a compartmental model of 18F-choline in order to evaluate its biokinetics and so to describe the temporal variation of the radiopharmaceuticals' uptake in and clearance from organs and tissues.Methods: Ten patients were considered in this study. A commercially available tool for compartmental analysis (SAAM II) was used to model the values of activity concentrations in organs and tissues obtained from PET images or from measurements of collected blood and urine samples.Results: A linear compartmental model of the biokinetics of the radiopharmaceutical was initially developed. It features a central compartment (blood) exchanging with organs. The structure describes explicitly liver, kidneys, spleen, blood and urinary excretion. The linear model tended to overestimate systematically the activity in the liver and in the kidney compartments in the first 20 min post-administration. A nonlinear process of kinetic saturation was considered, according to the typical Michaelis–Menten kinetics. Therefore nonlinear equations were added to describe the flux of 18F-choline from blood to liver and from blood to kidneys. The nonlinear model showed a tendency for improvement in the description of the activity in liver and kidneys, but not for the urine.Conclusions: The simple linear model presented is not able to properly describe the biokinetics of 18F-choline as measured in prostatic cancer patients. The introduction of nonlinear kinetics, although based on physiologically plausible assumptions, resulted in nonsignificant improvements of the model predictive power.

Enhanced antiproliferative effects of combination hexokinase II shRNA and NIS gene therapy on vascular smooth muscle cells

2011-09-28

Abstract: Introduction: This study was designed to determine the antiproliferative effects of combination gene therapy using sodium iodide symporter (NIS)-based radioiodine and lentivirus-mediated short hairpin RNA (shRNA) against hexokinase II (HKII) on vascular smooth muscle cells (VSMCs).Methods: A7r5 rat VSMCs were stably transfected with a dual-expression vector of NIS and Fluc (A7r5-NL cells). Functional assessment was performed by radioiodine uptake assay, luciferase assay and confocal microscopy. After exposure to lentivirus-HKII-shRNA, the 18F-FDG uptake test and HK activity assay were performed. The effects of combination therapy with 131I and lentivirus-HKII-shRNA on VSMCs were assessed with an in vitro clonogenic assay. In vivo bioluminescence and nuclear imaging were undertaken using a xenografted mouse model.Results: In vitro functional assessment confirmed expression of NIS and Fluc genes in A7r5-NL, but not in parent A7r5 cells. Transfection of lentivirus-HKII-shRNA resulted in a significant decrease in messenger RNA expression of the HKII gene, 18F-FDG uptake and HK activity. The cell survival rate of A7r5-NL decreased to 61.9% and 90.5% by single therapy with 7.4 MBq of 131I or lentivirus-HKII-shRNA, respectively, and further decreased to 42.9% by combined therapy (P<.05). In vivo bioluminescent and gamma camera images clearly demonstrated optical signals and 99mTc pertechnetate uptake at the site of A7r5-NL cell inoculation in nude mice.Conclusion: The enhanced antiproliferative effect on VSMCs was achieved by a combination of NIS-based radioiodine and lentivirus-mediated HKII shRNA gene therapy. Successful demonstration of in vivo dual reporter gene imaging assures the potential for further application in an animal model.

Characterization of 4-[18F]-ADAM as an imaging agent for SERT in non-human primate brain using PET: a dynamic study

2011-12-02

Abstract: Introduction: Serotonin transporter (SERT) has been associated with many psychiatric diseases. This study investigated the biodistribution of a serotonin transporter imaging agent, N,N-dimethyl-2-(2-amino-4-18F-fluorophenylthio)benzylamine (4-[18F]-ADAM), in nonhuman primate brain using positron emission tomography (PET).Methods: Six and four Macaca cyclopis monkeys were used to determine the transit time (i.e., time necessary to reach biodistribution equilibrium) and the reproducibility of 4-[18F]-ADAM biodistribution in the brain, respectively. The sensitivity and specificity of 4-[18F]-ADAM binding to SERT were evaluated in one monkey challenged with different doses of fluoxetine and one monkey treated with 3,4-methylendioxymethamphetamine (MDMA). Dynamic PET imaging was performed for 3 h after 4-[18F]-ADAM intravenous bolus injection. The specific uptake ratios (SURs) in the midbrain (MB), thalamus (TH), striatum (ST) and frontal cortex (FC) were calculated.Results: The distribution of 4-[18F]-ADAM reached equilibrium 120–150 min after injection. The mean SURs were 2.49±0.13 in MB, 1.59±0.17 in TH, 1.35±0.06 in ST and 0.34±0.03 in FC, and the minimum variability was shown 120–150 min after 4-[18F]-ADAM injection. Using SURs and intraclass coefficient of correlation, the test/retest variability was under 8% and above 0.8, respectively, in SERT-rich areas. Challenge with fluoxetin (0.75–2 mg) dose-dependently inhibited the SURs in various brain regions. 4-[18F]-ADAM binding was markedly reduced in the brain of an MDMA-treated monkey compared to that in brains of normal controls.Conclusion: 4-[18F]-ADAM appears to be a highly selective radioligand for imaging SERT in monkey brain.

[11C]Acetate rest–stress protocol to assess myocardial perfusion and oxygen consumption reserve in a model of congestive heart failure in rats

2011-11-14

Abstract: This study describes an [11C]acetate rest–stress method to obtain an indirect estimate of myocardial blood flow (MBF) and myocardial oxygen consumption (MVO2) in rats. Doxorubicin cardiotoxicity was used to test the usefulness of this approach for the assessment of congestive heart failure.Methods: [11C]Acetate rest–stress studies have been used in clinical research to assess the capacity of the coronary arteries to respond to stress. In this article, we used this approach to assess the cardiotoxicity of doxorubicin in a rat model. The method was first validated in a group of healthy rats and then used to follow the effect of doxorubicin chemotherapy on cardiac function. The effect of doxorubicin on myocardial perfusion and oxygen consumption reserve was measured at rest and under dobutamine stimulation.Results: Validation of the protocol showed a good correlation between the MBF and MVO2 (r2=.68). The doxorubicin-treated group showed a significant (P=.04) decrease in cardiovascular perfusion reserve at 1.3±0.2 compared with the control animals at 1.6±0.2. Similar results were obtained for the MVO2 reserve (treated 1.8±0.4 vs. controls 2.3±0.3; P=.02).Conclusions: We describe an [11C]acetate PET rest–stress protocol for the assessment of congestive heart failure in rats and its application to the follow-up of cardiotoxicity under doxorubicin chemotherapy. This is a rapid and reliable approach to the measurement of cardiac perfusion and oxygen consumption reserve that could be applied to the development of new strategies to reduce the cardiotoxicity of anthracycline.

Simplified quantification and whole-body distribution of [18F]FE-PE2I in nonhuman primates: prediction for human studies

2011-10-28

Abstract: Introduction: [18F]FE-PE2I is a promising dopamine transporter (DAT) radioligand. In nonhuman primates, we examined the accuracy of simplified quantification methods and the estimates of radiation dose of [18F]FE-PE2I.Methods: In the quantification study, binding potential (BPND) values previously reported in three rhesus monkeys using kinetic and graphical analyses of [18F]FE-PE2I were used for comparison. BPND using the cerebellum as reference region was obtained with four reference tissue methods applied to the [18F]FE-PE2I data that were compared with the kinetic and graphical analyses. In the whole-body study, estimates of adsorbed radiation were obtained in two cynomolgus monkeys.Results: All reference tissue methods provided BPND values within 5% of the values obtained with the kinetic and graphical analyses. The shortest imaging time for stable BPND estimation was 54 min. The average effective dose of [18F]FE-PE2I was 0.021 mSv/MBq, similar to 2-deoxy-2-[18F]fluoro-d-glucose.Conclusions: The results in nonhuman primates suggest that [18F]FE-PE2I is suitable for accurate and stable DAT quantification, and its radiation dose estimates would allow for a maximal administered radioactivity of 476 MBq in human subjects.

Radiation dose estimates for carbon-11-labelled PET tracers

2011-10-28

Abstract: Introduction: Carbon-11-labelled positron emission tomography (PET) tracers commonly used in biomedical research expose subjects to ionising radiation. Dosimetry is the measurement of radiation dose, but also commonly refers to the estimation of health risk associated with ionising radiation. This review describes radiation dosimetry of carbon-11-labelled molecules in the context of current PET research and the most widely used regulatory guidelines.Methods: A MEDLINE literature search returned 42 articles; 32 of these were based on human PET data dealing with radiation dosimetry of carbon-11 molecules. Radiation burden expressed as effective dose and maximum absorbed organ dose was compared between tracers.Results: All but one of the carbon-11-labelled PET tracers have an effective dose under 9 μSv/MBq, with a mean of 5.9 μSv/MBq. Data show that serial PET scans in a single subject are feasible for the majority of radiotracers.Conclusion: Although differing in approach, the two most widely used regulatory frameworks (those in the USA and the EU) do not differ substantially with regard to the maximum allowable injected activity per PET study. The predictive validity of animal dosimetry models is critically discussed in relation to human dosimetry. Finally, empirical PET data are related to human dose estimates based on homogenous distribution, generic models and maximum cumulated activities. Despite the contribution of these models to general risk estimation, human dosimetry studies are recommended where continued use of a new PET tracer is foreseen.

2012-02-01

Nuclear Medicine and Biology

Editorial Board

Synthesis and evaluation of [18F]exendin (9–39) as a potential biomarker to measure pancreatic β-cell mass

Radiolabeled Cu-ATSM as a novel indicator of overreduced intracellular state due to mitochondrial dysfunction: studies with mitochondrial DNA-less ρ0 cells and cybrids carrying MELAS mitochondrial DNA mutation

Evaluation of copper-64-labeled somatostatin agonists and antagonist in SSTr2-transfected cell lines that are positive and negative for p53: implications for cancer therapy

PET study using [11C]FTIMD with ultra-high specific activity to evaluate I2-imidazoline receptors binding in rat brains

Studies of the myocardial uptake and excretion mechanisms of a novel 99mTc heart perfusion agent

Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma

Difficulties in dopamine transporter radioligand PET analysis: the example of LBT-999 using [18F] and [11C] labelling: Part I: PET studies

Synthesis and evaluation of a C-6 alkylated pyrimidine derivative for the in vivo imaging of HSV1-TK gene expression

Radiohalogenated 4-anilinoquinazoline-based EGFR-TK inhibitors as potential cancer imaging agents

Nonlinear compartmental model of 18F-choline

Enhanced antiproliferative effects of combination hexokinase II shRNA and NIS gene therapy on vascular smooth muscle cells

Characterization of 4-[18F]-ADAM as an imaging agent for SERT in non-human primate brain using PET: a dynamic study

[11C]Acetate rest–stress protocol to assess myocardial perfusion and oxygen consumption reserve in a model of congestive heart failure in rats

Simplified quantification and whole-body distribution of [18F]FE-PE2I in nonhuman primates: prediction for human studies

Radiation dose estimates for carbon-11-labelled PET tracers

Table of Contents