Nuclear Medicine and Biology

Editorial Board

2010-02-01

111In- or 99mTc-labeled recombinant VEGF bioconjugates: in vitro evaluation of their cytotoxicity on porcine aortic endothelial cells overexpressing Flt-1 receptors

Conrad Chan, Zhongli Cai, Ruifen Su, Raymond M. Reilly — 2009-11-06

Abstract: Introduction: The aims of this study were to (a) synthesize and characterize a novel vascular endothelial growth factor (VEGF-2K) recombinant protein expressed in Pichia pastoris and (b) compare its cytotoxicity when labeled with the Auger electron emitter 111In or 99mTc, both of which are in the nanometer–micrometer range, toward porcine aortic endothelial (PAE) cells transfected with the flt-1 gene to overexpress Flt-1 receptors (PAE-Flt-1).Methods: The gene for the VEGF165 isoform was fused to a sequence encoding an extended flexible peptide (KGGGGSK) with two accessible lysines for preferential derivatization with diethylenetriaminepentaacetic acid (DTPA) for complexing 111In and a sequence for a His6 affinity tag that bound the [99mTc(CO)3(H2O)3]+ tricarbonyl complex. P. pastoris strain KM71H was transfected with the recombinant gene, the VEGF-2K protein expressed with methanol induction, and then purified by metal-affinity chromatography. VEGF-2K was modified with 13-mer peptides [CGYGPKKKRKVGG] containing the nuclear localization sequence (NLS) of SV-40 large T-antigen (underlined) to promote nuclear uptake following its receptor-mediated internalization.Results: 99mTc-DTPA-VEGF-2K bound strongly and preferentially to PAE-Flt-1 cells compared with non-transfected PAE cells, but NLS modification diminished the ratio of PAE-Flt-1 to PAE binding to 2.3-fold. Nuclear accumulation of 99mTc-labeled DTPA-VEGF-2K was not enhanced by NLS modification but was enhanced by 1.5-fold for 111In-DTPA-VEGF-2K-NLS. However, confocal microscopy revealed intranuclear distribution of DTPA-VEGF-2K-NLS, whereas DTPA-VEGF-2K distribution was mainly perinuclear. 111In-DTPA-VEGF-2K-NLS was the most cytotoxic to PAE-Flt-1 cells, reducing their clonogenic survival by 4-fold. 111In-DTPA-VEGF-2K, 99mTc-DTPA-VEGF-2K or 99mTc-DTPA-VEGF-2K-NLS had less effect on the clonogenic survival of PAE-Flt-1 or PAE cells. The strong cytotoxicity of 111In-DTPA-VEGF-2K-NLS toward PAE-Flt-1 cells was associated with a 27-fold increase in nuclear foci of immunofluorescence for phosphorylated histone-2AX corresponding to sites of unrepaired DNA double-strand breaks. Monte Carlo modeling revealed that radionuclide decay in the nucleus would provide a 5-fold higher radiation absorbed dose for 111In than for 99mTc, explaining their differential cytotoxicity, and intranuclear localization would amplify the radiation dose delivered by 111In by 3-fold, explaining the greater potency of 111In-DTPA-VEGF-2K-NLS compared with 111In-DTPA-VEGF-2K.Conclusions: We conclude that targeted Auger electron radiotherapy aimed at Flt-1 receptors is a promising strategy that should be explored further for treatment of tumors in which this angiogenic pathway is up-regulated. 111In is a more cytotoxic radionuclide than 99mTc, unless DNA delivery can be achieved, due to the short range of the electrons emitted.

Preliminary studies of 99mTc-BnAO and its analogues: synthesis, radiolabeling and in vitro cell uptake

Xin Sun, Taiwei Chu, Xiangyun Wang — 2009-11-04

Abstract: Introduction: 99mTc-BnAO is one of the nonnitroimidazole hypoxia markers with the highest citation and could be potentially useful in both oncology and other clinical applications. However, it appears inferior in vitro due to lower absolute accumulation and smaller anoxic/normoxic uptake ratio. It is possible that the analogues of 99mTc-BnAO have higher hypoxia selectivity after the ligand of 99mTc-BnAO is modified.Methods: 2,2′-(1,4-Diaminobutane)bis(2-methyl-3-butanone) dioxime (BnAO or HL91) and three novel analogues were synthesized and radiolabeled with technetium-99m. The cellular uptake of the radiolabeled complexes was determined in murine sarcoma S180 cell lines under anoxic and normoxic conditions.Results: 99mTc-BnAO and its three novel analogues continuously accumulated in anoxic cells but not in normoxic ones, while the analogues showed earlier hypoxia selectivity and greater anoxic/normoxic differential.Conclusions: The analogues are superior to 99mTc-BnAO in terms of in vitro hypoxia selectivity and are viable candidates for further development as new nonnitroimidazole hypoxia markers in the future.

Hypoxia-induced redox alterations and their correlation with 99mTc-MIBI and 99mTc-HL-91 uptake in colon cancer cells

2009-12-16

Abstract: Colorectal cancer is one of the most common malignancies in the Western world and is an example of a solid tumour in which hypoxia is a common feature and develops because of the inability of the vascular system to supply adequate amounts of oxygen to growing tumours. Hypoxia effects on tumour cell biology can be detected and characterized using different methods. The use of imaging with γ-emitting radionuclides to detect hypoxic tissue was first suggested by Chapman in 1979 [N Engl J Med 301 (1979) 1429–1432]. 99mTc-4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime, also known as 99mTc-HL-91, has been among the most studied hypoxia markers.The objective of this study was to correlate the uptake of 99mTc-HL-91 and 99mTc-MIBI in colon cancer cells under normoxic and hypoxic conditions and to compare this information with some parameters such as oxidative stress and mitochondrial dysfunction of the cells analyzed by flow cytometry.Our results show that the in vitro 99mTc-HL-91 uptake is higher in hypoxic conditions, which is confirmed by the decreased uptake of 99mTc-MIBI. Flow cytometry results demonstrate that hypoxic conditions used are not enough to induce cellular death, but are responsible for the alterations in the intracellular redox environment, namely, increase of ROS production, proteic pimonidazol-derived adduct formation and alteration in the mitochondrial membrane permeability. Therefore, these results confirm that 99mTc-HL-91 is a radiopharmaceutical with favourable characteristics for detecting hypoxia.

An improved radiosynthesis of [18F]AV-133: a PET imaging agent for vesicular monoamine transporter 2

Lin Zhu, Yajing Liu, Karl Plössl, Brian Lieberman, Jingying Liu, Hank F. Kung — 2009-12-16

Abstract: Introduction: Recently, a PET tracer, 9-[18F]fluoropropyl-(+)-dihydrotetrabenazine ([18F]AV-133), targeting vesicular monoamine transporter 2 (VMAT2) in the central nervous system has been reported. It is currently under Phase II clinical trials to establish its usefulness in the diagnosis of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. The radiolabeling of [18F]AV-133, nucleophilic fluorination reaction and potential effects of pseudo-carrier were evaluated by in vivo biodistribution.Methods: The preparation of [18F]AV-133 was evaluated under different conditions, specifically by employing different precursors (–OTs or –Br as the leaving group at the 9-propoxy position), reagents (K222/K2CO3 vs. tributylammonium bicarbonate) and solvents (acetonitrile vs. DMSO), reaction temperature and reaction time. With optimized conditions from these experiments, radiosynthesis and purification with solid-phase extraction (SPE) of [18F]AV-133 were performed by an automated nucleophilic [18F]fluorination module. In vivo biodistribution in mice on [18F]AV-133 purified by either HPLC (no-carrier-added) or the SPE method (containing a pseudo-carrier) was performed and the results compared.Results: Under a mild fluorination condition (heating at 115°C for 5 min in dimethyl sulfoxide), [18F]AV-133 was obtained in a high yield using either –OTs or –Br as the leaving group. However, the –OTs precursor gave better radiochemical yields (>70%, thin layer chromatography analysis) compared to those of the –Br precursor. The optimized reaction conditions were successfully implemented to an automated nucleophilic fluorination module. Labeling and purification of [18F]AV133 were readily achieved via this automatic module in good radiochemical yield of 21–41% (n=10) in 40 min. The radiochemical purity was larger than 95%. Biodistribution of SPE-purified product (containing a pseudo-carrier) in mice showed a high striatum/cerebellum ratio (4.18±0.51), which was comparable to that of HPLC-purified [18F]AV-133 (4.51±0.10).Conclusions: The formation of [18F]AV-133 was evaluated under different labeling conditions. These improved labeling conditions and SPE purification were successfully implemented into an automated synthesis module. This offers a short preparation time (about 40 min), simplicity in operation and ready applicability for routine clinical operation.

A 1-methyl-4-piperidinyl cytectrene carboxylate labeled by the technetium 99m, a radiotracer for rat brain acetylcholinesterase activity

2009-11-06

Abstract: Alzheimer's disease (AD) is a degenerative neurological disorder that causes progressive and irreversible loss of connections between brain cells and loss of mental functions.Clinical and postmortem studies show that the biochemical changes in brains of AD patients include decrease in acetylcholinesterase (AChE) activity.Our aim was to study AChE activity using piperidinyl ester labelled with technetium-99m. In vivo and in vitro studies demonstrated that labelled piperidinyl ester was a substrate for AChE. The hydrolytic rate of this substrate was measured and the specificity was evaluated using the inhibitor BW284c51.The rhenium analogues of the technetium-labelled substrate were used to determine the affinity constant (Km) and the maximum reaction velocity (Vmax) because of the high specific activity of technetium. The high hydrolytic rate and high specificity of the substrate for AChE make it suitable as an in vivo radiotracer for studying AChE activity in the brain.

Formulation of 68Ga BAPEN kit for myocardial positron emission tomography imaging and biodistribution study

2009-11-30

Abstract: Introduction: Tris(4,6-dimethoxysalicylaldimine)-N,N′-bis(3-aminopropyl)-N,N′-ethylenediamine (BAPEN), a tris(salicylaldimine) derivative, is a heart positron emission tomography (PET) agent when labeled with 68Ga. However, its labeling requires complicated and time-consuming procedures. In this study, the authors formulated a new BAPEN kit for convenient 68Ga labeling.Methods: BAPEN (0.25 mg) kits were prepared by dispensing its solution in 1 M sodium acetate buffer (pH 5.5) into sterile vials and lyophilization. The prepared kits were labeled with generator-eluted 68Ga in 0.1 N HCl. Stability in human serum was tested. Expiration date was determined by accelerated testing according to US Food and Drug Administration guidelines. A Biodistribution study was performed in normal mice after injection via tail vein.Results: The prepared kits achieved radiolabeling efficiencies in excess of 95% and showed a shelf-life of 98 days at 25°C and 64.3 months at 4°C. 68Ga-BAPEN was found to be stable in human serum at 37°C for at least 1 h. Furthermore, a biodistribution study revealed high heart uptake (10.8% ID/g, 1 h).Conclusions: The authors developed a BAPEN kit for convenient labeling with 68Ga. The 68Ga-BAPEN showed high stability and excellent biodistribution results in normal mice, which is required for myocardial PET imaging.

Tumor uptake of 68Ga-DOTA-Tyr3-octreotate: animal PET studies of tumor flow and acute somatostatin receptor modulation in the CA20948 rat model

2009-11-09

Abstract: Introduction: Factors determining the in vivo uptake of radiolabeled somatostatin analogs by neuroendocrine tumors are poorly known. The aim is to evaluate in vivo tumor perfusion and regulation of somatostatin receptors (sstr) following acute exposure to octreotide, in an animal model of neuroendocrine tumor.Methods: H215O flow studies were performed in 8 CA20948 tumor-bearing rats and another 36 rats underwent three [68Ga]-DOTA-Tyr3-octreotate imaging sessions at 24-h intervals. After baseline (Day 0) imaging, scanning was repeated on Day 1 after octreotide injection (175 μg/kg), with a variable delay: no injection (controls, n=7), coinjection (n=6), and octreotide injection 20 min (n=7), 2 h (n=8) and 4 h (n=8) before imaging. Repeat images without octreotide was performed at Day 2 followed by sacrifice and tumor counting.Results: H215O studies failed to measure quantitative tumor perfusion in this model. On Day 1, ratio of tumor uptake to Day 0 was 1.2±0.3 in controls; 0.6±0.2 in the coinjection group; 0.9±0.2, 1.1±0.1 and 1.2±0.2 in the other groups, respectively. Uptake in the coinjection group showed a statistically significant reduction of tumor uptake (P<.0001). All groups showed increased uptake on Day 2, without statistical differences between groups. In vivo tumor counts showed good correlation with ex vivo countings (R2=0.946).Conclusion: Acute exposure to unlabeled octreotide in this neuroendocrine tumor model results in a rapid recycling or resynthesis of sstr. Positron emission tomography (PET) allowed to reliably assess quantitative uptake of [68Ga]-DOTA-Tyr3-octreotate over time in the same animal, but failed in this model to measure tumor perfusion.

Preparation and in vivo evaluation of radioiodinated closo-decaborate(2-) derivatives to identify structural components that provide low retention in tissues

D. Scott Wilbur, Ming-Kuan Chyan, Donald K. Hamlin, Matthew A. Perry — 2009-11-20

Abstract: Introduction: In vivo deastatination of 211At-labeled biomolecules can severely limit their use in endoradiotherapy. Our studies have shown that the use of closo-decaborate(2-) moiety for 211At-labeling of biomolecules provides high in vivo stability towards deastatination. However, data from those studies have also been suggestive that some astatinated closo-decaborate(2-) catabolites may be retained in tissues. In this study, we investigated the in vivo distributions of several structurally simple closo-decaborate(2-) derivatives to gain information on the effects of functional groups if catabolites are released into the blood system from the carrier biomolecule.Methods: Thirteen closo-decaborate(2-) derivatives were synthesized and radioiodinated for evaluation. Tissue concentrations of the radioiodinated compounds were obtained in groups of five mice at 1 and 4 h postinjection (pi). Dual-label (125I and 131I) experiments permitted evaluation of two compounds in each set of mice.Results: All of the target compounds were readily synthesized. Radioiodination reactions were conducted with chloramine-T and Na[125/131I]I in water to give high yields (75–96%) of the desired compounds. Biodistribution data at 1 and 4 h pi (representing catabolites released into the blood system) showed small differences in tissue concentrations for some compounds, but large differences for others. The results indicate that formal (overall) charge on the compounds could not be used as a predictor of tissue localization or retention. However, derivatives containing carboxylate groups generally had lower tissue concentrations. Acid cleavable hydrazone functionalities appeared to be the best candidates for further study.Conclusions: Further studies incorporating hydrazone functionalities into pendant groups for biomolecule radiohalogenation are warranted.

C-kit-targeted imaging of gastrointestinal stromal tumor using radiolabeled anti-c-kit monoclonal antibody in a mouse tumor model

2009-11-30

Abstract: Introduction: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor arising from the gastrointestinal tract and highly expresses mutated c-kit. We aimed to develop a specific and sensitive method for detecting GISTs using radiolabeled anti-c-kit monoclonal antibody.Methods: A mutated c-kit-expressing cell clone was established by transfecting an expressing vector of mutated c-kit gene into HEK293 human embryonic kidney cells. The tumors were developed by inoculating c-kit-expressing cells into nude mice. 125I- and 111In-labeled anti-c-kit antibodies (12A8 and 41A11) were evaluated in vitro by cell binding, competitive inhibition and cellular internalization assays, and in vivo by biodistribution and imaging studies in tumor-bearing mice.Results: Both 125I- and 111In-labeled antibodies showed specific binding with c-kit-expressing cells with high affinity (dissociation constants = 2.2–7.1×109 M−1). Internalization assay showed that 125I-labeled antibodies were rapidly internalized and dehalogenated, with the release of 125I from the cells, resulting in reduction of cell-associated radioactivity with time. In contrast, 111In-labeled antibody was internalized but did not result in the reduced radioactivity associated with tumor cells. Reflecting this phenomenon, the in vivo tumor uptake of 125I-labeled antibody was low on Day 1, further decreasing with time, while tumor uptake of 111In-labeled antibody was high on Day 1, further increasing with time. The xenografted tumor was clearly visualized by scintigraphy after injection of 111In-labeled antibody.Conclusion: The anti-c-kit monoclonal antibody labeled with a metal radionuclide would be promising for c-kit-targeted imaging of GISTs.

Stimulation of 125I-3-iodo-α-methyl-l-tyrosine uptake in Chinese hamster ovary (CHO-K1) cells by tyrosine esters

2009-11-04

Abstract: Introduction: Transport of the amino acid analog 123I-3-iodo-α-methyl-l-tyrosine, which is used in clinical SPECT imaging, occurs mainly via l-type amino acid transporter type 1 (LAT1; an amino acid exchanger). As LAT1 is highly expressed in actively proliferating tumors, we made a preliminary investigation of the effects of amino acid esters on enhancement of 125I-3-iodo-α-methyl-l-tyrosine (IMT) uptake via LAT1 in Chinese hamster ovary (CHO-K1) cells.Methods: Because the sequence of the CHO-K1 LAT1 gene is not available, we confirmed LAT1 expression through IMT (18.5 kBq) uptake mechanisms using specific inhibitors. l-Gly, l-Ser, l-Leu, l-Phe, l-Met, l-Tyr, d-Tyr, l-Val and l-Lys ethyl/methyl esters were tested in combination with IMT. Time-course studies over a 3-h period were conducted, and the concentration dependence of l-Tyr ethyl and methyl esters (0.001 to 10 mM) in combination with IMT was also examined. For a proof of de-esterification of l- and D-Tyr ethyl and methyl esters in the cells (by enzymatic attack or other cause), the concentration of l- and d-Tyr was analyzed by high-performance liquid chromatography of the esters in phosphate buffer (pH 7.4) and cell homogenates at 37°C or under ice-cold conditions.Results: Inhibition tests suggested that LAT1 is involved in IMT uptake by CHO-K1 cells. Co-administration of 1 mM of l-Tyr ethyl or methyl ester with IMT produced the greatest enhancement. The de-esterification reaction was stereo selective and temperature dependent in the homogenate. De-esterification kinetics were very fast in the homogenate and very slow in the phosphate buffer.Conclusions: The l-Tyr ethyl or methyl esters were the most effective enhancers of IMT uptake into CHO-K1 cells and acted by trans-stimulation of the amino acid exchange function of LAT1. This result suggests that de-esterification in the cells may be caused by enzymatic attack. We will use IMT and l-Tyr ethyl or methyl esters to examine LAT1 function in tumor cells or tissues in vivo.

Uptake of 3-[125I]iodo-α-methyl-l-tyrosine into colon cancer DLD-1 cells: characterization and inhibitory effect of natural amino acids and amino acid-like drugs

2009-11-30

Abstract: Introduction: We examined 3-[123I]iodo-α-methyl-l-tyrosine ([123I]IMT) uptake and inhibition by amino acids and amino acid-like drugs in the human DLD-1 colon cancer cell line, to discuss correlation between the inhibition effect and structure.Methods: Expression of relevant neutral amino acid transporters was examined by real-time PCR with DLD-1 cells. The time course of [125I]IMT uptake, contributions of transport systems, concentration dependence and inhibition effects by amino acids and amino acid-like drugs (1 mM) on [125I]IMT uptake were examined.Results: Expression of system L (4F2hc, LAT1 and LAT2), system A (ATA1, ATA2) and system ASC (ASCT1) was strongly detected; system L (LAT3, LAT4) and MCT8 were weakly detected; and B0AT was not detected. [125I]IMT uptake in DLD-1 cells involved Na+-independent system L primarily and Na+-dependent system(s). Uptake of [125I]IMT in Na+-free buffer followed Michaelis–Menten kinetics, with a Km of 78 μM and Vmax of 333 pmol/106 cells per minute. Neutral d- and l-amino acids with branched or aromatic large side chains inhibited [125I]IMT uptake. Tyrosine analogues, tryptophan analogues, l-phenylalanine and p-halogeno-l-phenylalanines, and gamma amino acids [including 3,4-dihydroxy-l-phenylalanine (l-DOPA), dl-threo-β-(3,4-dihydroxyphenyl)serine (DOPS), 4-[bis(2-chloroethyl)amino]-l-phenylalanine and 1-(aminomethyl)-cyclohexaneacetic acid] strongly inhibited [125I]IMT uptake, but l-tyrosine methyl ester and R(+)/S(−)-baclofen weakly inhibited uptake. The substrates of system ASC and A did not inhibit [125I]IMT uptake except l-serine and d/l-cysteine.Conclusions: [125I]IMT uptake in DLD-1 cells involves mostly LAT1 and its substrates' (including amino acid-like drugs derived from tyrosine, tryptophan and phenylalanine) affinity to transport via LAT1. Whether transport of gamma amino acid analogues is involved in LAT1 depends on the structure of the group corresponding to the amino acid residue. Beta-hydroxylation may confer reduction of transport affinity of tyrosine analogues via LAT1.

High-resolution imaging of brain 5-HT1B receptors in the rhesus monkey using [11C]P943

2009-12-02

Abstract: The serotonin 5-HT1B receptors regulate the release of serotonin and are involved in various disease states, including depression and schizophrenia. The goal of the study was to evaluate a high affinity and high selectivity antagonist, [11C]P943, as a positron emission tomography (PET) tracer for imaging the 5-HT1B receptor. [11C]P943 was synthesized via N-methylation of the precursor with [11C]methyl iodide or [11C]methyl triflate using automated modules. The average radiochemical yield was approx. 10% with radiochemical purity of >99% and specific activity of 8.8±3.6 mCi/nmol at the end-of-synthesis (n=37). PET imaging was performed in non-human primates with a high-resolution research tomograph scanner with a bolus/infusion paradigm. Binding potential (BPND) was calculated using the equilibrium ratios of regions to cerebellum. The tracer uptake was highest in the globus pallidus and occipital cortex, moderate in basal ganglia and thalamus, and lowest in the cerebellum, which is consistent with the known brain distribution of 5-HT1B receptors. Infusion of tracer at different specific activities (by adding various amount of unlabeled P943) reduced BPND values in a dose-dependent manner, demonstrating the saturability of the tracer binding. Blocking studies with GR127935 (2 mg/kg iv), a selective 5-HT1B/5-HT1D antagonist, resulted in reduction of BPND values by 42-95% across regions; for an example, in occipital region from 0.71 to 0.03, indicating a complete blockade. These results demonstrate the saturability and specificity of [11C]P943 for 5-HT1B receptors, suggesting its suitability as a PET radiotracer for in vivo evaluations of the 5-HT1B receptor system in humans.

Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of 177Lu-EDTMP, a potential bone pain palliation agent

2009-11-13

Abstract: Introduction: Radionuclide therapy (RNT) is an effective method for bone pain palliation in patients suffering from bone metastasis. Due to the long half-life, easy production and relatively low β− energy, 177Lu [T1/2=6.73 days, Eβmax=497 keV, Eγ=113 keV (6.4%), 208 keV (11%)]-based radiopharmaceuticals offer logistical advantage for wider use. This paper reports the results of a multispecies biodistribution and toxicity studies of 177Lu-EDTMP to collect preclinical data for starting human clinical trials.Methods: 177Lu-EDTMP with radiochemical purity greater than 99% was formulated by using a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH). Biodistribution studies were conducted in mice and rabbits. Small animal imaging was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels of activity (9.25 through 37 MBq/kg body weight) of 177Lu-EDTMP were injected in four groups of three dogs each to study the toxicological effects.Results: 177Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41% of the injected activity in bone with terminal elimination half-life of 2130 and 1870 h in mice and rabbits, respectively) with a peak uptake during 1–3 h. Excretion of the radiopharmaceutical was through the urinary system. Imaging studies showed that all species (mouse, rat, rabbit and dog) take up the compound in regions of remodeling bone, while kidney retention is not visible after 1 day postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight) led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi with no toxicity.Conclusion: The protracted effective half-life of 177Lu-EDTMP in bone supports that modifying the EDTMP molecule by introducing 177Lu does not alter its biological behaviour as a specific bone-seeking tracer. Species-specific pharmacokinetic behavior differences were observed. Toxicity studies in dogs did not show any biological adverse effects. The studies demonstrate that 177Lu-EDTMP is a promising radiopharmaceutical that can be further evaluated for establishing as a radiopharmaceutical for human use.

Three-region MRI-based whole-body attenuation correction for automated PET reconstruction

2009-12-07

Abstract: Introduction: In this study we proposed and developed a simple attenuation mapping approach based on magnetic resonance imaging (MRI) for the purpose of reconstructing positron emission tomography (PET) images in PET/MRI imaging devices.Methods: After experimental development, an in vivo calibration was performed by whole-body scanning of five beagles on both a PET/CT and an MRI. The attenuation was determined by using an automated segmentation algorithm to segment regions of background, lung, soft tissue and bone, and assigning them values of 0.002, 0.030, 0.098 and 0.130 cm−1, respectively.Results: The CT-attenuated and MRI-attenuated PET images had average standardized uptake values (SUVs) that differed by 1–6% for most regions of interest (ROIs). Also, mean relative differences (MRDs) between the images were between 5% and 9% for most regions. The only exception is bone, where the three-region MRI-attenuated PET images had an SUV 10% less on average than the CT-attenuation images, and the MRD averaged 14%. Also, additional segmentation of the bone in the four-region MRI-attenuated PET images reduced the SUV difference to 3% and the MRD to 6%.Conclusion: Therefore, despite the improvements in the four-region segmentation, the three-region segmentation, without delineation of osseous tissues, produces high-quality images that are sufficient for most expected clinical and research purposes.

2010-02-01

Nuclear Medicine and Biology

Editorial Board

111In- or 99mTc-labeled recombinant VEGF bioconjugates: in vitro evaluation of their cytotoxicity on porcine aortic endothelial cells overexpressing Flt-1 receptors

Preliminary studies of 99mTc-BnAO and its analogues: synthesis, radiolabeling and in vitro cell uptake

Hypoxia-induced redox alterations and their correlation with 99mTc-MIBI and 99mTc-HL-91 uptake in colon cancer cells

An improved radiosynthesis of [18F]AV-133: a PET imaging agent for vesicular monoamine transporter 2

A 1-methyl-4-piperidinyl cytectrene carboxylate labeled by the technetium 99m, a radiotracer for rat brain acetylcholinesterase activity

Formulation of 68Ga BAPEN kit for myocardial positron emission tomography imaging and biodistribution study

Tumor uptake of 68Ga-DOTA-Tyr3-octreotate: animal PET studies of tumor flow and acute somatostatin receptor modulation in the CA20948 rat model

Preparation and in vivo evaluation of radioiodinated closo-decaborate(2-) derivatives to identify structural components that provide low retention in tissues

C-kit-targeted imaging of gastrointestinal stromal tumor using radiolabeled anti-c-kit monoclonal antibody in a mouse tumor model

Stimulation of 125I-3-iodo-α-methyl-l-tyrosine uptake in Chinese hamster ovary (CHO-K1) cells by tyrosine esters

Uptake of 3-[125I]iodo-α-methyl-l-tyrosine into colon cancer DLD-1 cells: characterization and inhibitory effect of natural amino acids and amino acid-like drugs

High-resolution imaging of brain 5-HT1B receptors in the rhesus monkey using [11C]P943

Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of 177Lu-EDTMP, a potential bone pain palliation agent

Three-region MRI-based whole-body attenuation correction for automated PET reconstruction

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