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1.
Dubois L Landuyt W Cloetens L Bol A Bormans G Haustermans K Labar D Nuyts J Grégoire V Mortelmans L 《European journal of nuclear medicine and molecular imaging》2009,36(2):209-218
Purpose The aim of this investigation was to quantitatively compare the novel positron emission tomography (PET) hypoxia marker 2-(2-nitroimidazol-1-yl)-N-(3[18F],3,3-trifluoropropyl)acetamide ([18F]EF3) with the reference hypoxia tracer [18F]fluoromisonidazole ([18F]FMISO).
Methods [18F]EF3 or [18F]FMISO was injected every 2 days into two separate groups of rats bearing syngeneic rhabdomyosarcoma tumours. In vivo PET analysis was done by drawing regions of interest on the images of selected tissues. The resulting activity data were
quantified by the percentage of injected radioactivity per gram tissue (%ID/g) and tumour to blood (T/B) ratio. The spatial
distribution of radioactivity was defined by autoradiography on frozen tumour sections.
Results The blood clearance of [18F]EF3 was faster than that of [18F]FMISO. The clearance of both tracers was slower in tumour tissue compared with other tissues. This results in increasing
T/B ratios as a function of time post tracer injection (p.i.). The maximal [18F]EF3 tumour uptake, compared to the maximum [18F]FMISO uptake, was significantly lower at 2 h p.i. but reached similar levels at 4 h p.i. The tumour uptake for both tracers
was independent of the tumour volume for all investigated time points. Both tracers showed heterogeneous intra-tumoural distribution.
Conclusions [18F]EF3 tumour uptake reached similar levels at 4 h p.i. compared with tumour retention observed after injection of [18F]FMISO at 2 h p.i. Although [18F]EF3 is a promising non-invasive tracer, it is not superior over [18F]FMISO for the visualisation of tumour hypoxia. No significant differences between [18F]EF3 and [18F]FMISO were observed with regard to the intra-tumoural distribution and the extra-tumoural tissue retention. 相似文献
2.
Verstappen CC Bloem BR Haaxma CA Oyen WJ Horstink MW 《European journal of nuclear medicine and molecular imaging》2007,34(4):502-507
Introduction Striatal postsynaptic D2 receptors in Parkinson’s disease (PD) are thought to be upregulated in the first years of the disease, especially contralateral
to the clinically most affected side. The aim of this study was to evaluate whether the highest striatal D2 binding is found contralateral to the most affected side in PD, and whether this upregulation can be used as a diagnostic
tool.
Methods Cross-sectional survey was undertaken of 81 patients with clinically asymmetric PD, without antiparkinsonian drugs and with
a disease duration of ≤5 years and 26 age-matched controls. Striatal D2 binding was assessed with [123I]IBZM SPECT, and severity of the presynaptic dopaminergic lesion with [123I]FP-CIT SPECT.
Results The mean striato-occipital ratio of [123I]IBZM binding was significantly higher in PD patients (1.56 ±0.09) than in controls (1.53 ±0.06). In PD patients, higher
values were found contralateral to the clinically most affected side (1.57 ±0.09 vs 1.55 ±0.10 ipsilaterally), suggesting
D2 receptor upregulation, and the reverse was seen using [123I]FP-CIT SPECT. However, on an individual basis only 56% of PD patients showed this upregulation.
Conclusion Our study confirms asymmetric D2 receptor upregulation in PD. However, the sensitivity of contralateral higher striatal [123I]IBZM binding is only 56%. Therefore, the presence of contralateral higher striatal IBZM binding has insufficient diagnostic
accuracy for PD, and PD cannot be excluded in patients with parkinsonism and no contralateral upregulation of D2 receptors, assessed with [123I]IBZM SPECT. 相似文献
3.
Shetty HU Zoghbi SS Liow JS Ichise M Hong J Musachio JL Halldin C Seidel J Innis RB Pike VW 《European journal of nuclear medicine and molecular imaging》2007,34(5):667-678
Purpose We aimed to determine the composition of radioactivity in rat brain after intravenous administration of the dopamine transporter
radioligand, [11C]PE2I.
Methods PET time-activity curves (TACs) and regional brain distribution ex vivo were measured using no-carrier-added [11C]PE2I. Carrier-added [11C]PE2I was administered to identify metabolites with high-performance liquid radiochromatography (RC) or RC with mass spectrometry
(LC-MS and MS-MS). The stability of [11C]PE2I was assessed in rat brain homogenates.
Results After peak brain uptake of no-carrier-added [11C]PE2I, there was differential washout rate from striata and cerebellum. Thirty minutes after injection, [11C]PE2I represented 10.9 ± 2.9% of the radioactivity in plasma, 67.1 ± 11.0% in cerebellum, and 92.5 ± 3.2% in striata, and
was accompanied by two less lipophilic radiometabolites. [11C]PE2I was stable in rat brain homogenate for at least 1 h at 37°C. LC-MS identified hydroxylated PE2I (1) (m/z 442) and carboxyl-desmethyl-PE2I (2) (m/z 456) in brain. MS-MS of 1 gave an m/z 442→424 transition due to H2O elimination, so verifying the presence of a benzyl alcohol group. Metabolite 2 was the benzoic acid derivative. Ratios of ex vivo measurements of [11C]PE2I, [11C]1, and [11C]2 in striata to their cognates in cerebellum were 6.1 ± 3.4, 3.7 ± 2.2 and 1.33 ± 0.38, respectively, showing binding selectivity
of metabolite [11C]1 to striata.
Conclusion Radiometabolites [11C]1 and [11C]2 were characterized as the 4-hydroxymethyl and 4-carboxyl analogs of [11C]PE2I, respectively. The presence of the pharmacologically active [11C]1 and the inactive [11C]2 is a serious impediment to successful biomathematical analysis. 相似文献
4.
Ekblad T Tran T Orlova A Widström C Feldwisch J Abrahmsén L Wennborg A Karlström AE Tolmachev V 《European journal of nuclear medicine and molecular imaging》2008,35(12):2245-2255
Purpose Affibody molecules are low molecular weight proteins (7 kDa), which can be selected to bind to tumour-associated target proteins
with subnanomolar affinity. Because of rapid tumour localisation and clearance from nonspecific compartments, Affibody molecules
are promising tracers for molecular imaging. Earlier, 99mTc-labelled Affibody molecules demonstrated specific targeting of tumour xenografts. However, the biodistribution was suboptimal
either because of hepatobiliary excretion or high renal uptake of the radioactivity. The goal of this study was to optimise
the biodistribution of Affibody molecules by chelator engineering.
Materials and methods Anti-HER2 ZHER2:342 Affibody molecules, carrying the mercaptoacetyl-glutamyl-seryl-glutamyl (maESE), mercaptoacetyl-glutamyl-glutamyl-seryl (maEES)
and mercaptoacetyl-seryl-glutamyl-glutamyl (maSEE) chelators, were prepared by peptide synthesis and labelled with 99mTc. The tumour-targeting capacity of these conjugates was compared with each other and with the best previously available
conjugate, 99mTc-maEEE-ZHER2:342, in nude mice bearing SKOV-3 xenografts. The tumour-targeting capacity of the most promising conjugate, 99mTc-maESE-ZHER2:342, was compared with radioiodinated ZHER2:342.
Results All novel conjugates demonstrated successful tumour targeting and a low degree of hepatobiliary excretion. The renal uptakes
of serine-containing conjugates, 33 ± 5, 68 ± 21 and 71 ± 10%IA/g, for99mTc-maESE-ZHER2:342, 99mTc-maEES-ZHER2:342 and 99mTc-maSEE-ZHER2:342, respectively, were significantly reduced in comparison with 99mTc-maEEE-ZHER2:342 (102 ± 13%IA/g). For 99mTc-maESE-ZHER2:342, a tumour uptake of 9.6 ± 1.8%IA/g and a tumour-to-blood ratio of 58 ± 6 were reached at 4 h p.i.
Conclusions A combination of serine and glutamic acid residues in the chelator sequence confers increased renal excretion and relatively
low renal uptake of 99mTc-labelled Affibody molecules. In combination with preserved targeting capacity, this improved imaging of targets in abdominal
area. 相似文献
5.
Juan P. Gambini Juan J. López Lerena Adriana Quagliata Juan C. Hermida Carlos Heuguerot Omar Alonso 《Annals of nuclear medicine》2008,22(9):817-819
Disease status assessment of neuroblastoma patients requires computed tomography (or magnetic resonance imaging), bone scan,
metaiodobenzylguanidine (MIBG) scan, bone marrow tests, and urine catecholamine measurements. There is no clinical experience
concerning the evaluation of these patients by means of technetium-99m (99mTc)-somatostatin analog scintigraphy. Furthermore, these radiopharmaceuticals are promising imaging agents owing to their
lower cost, availability, dosimetry, and ease of preparation. An 8-year-old boy already diagnosed with stage-IV neuroblastoma
received chemotherapy. In the follow-up, after obtaining the parents’ informed consent, iodin 131 (131I)-MIBG and 99mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-octreotide scans were done on separate days to evaluate tumor extension.
Even as the 131I-IBG scan showed mild diffuse uptake in the projection of both lung hili, the 99mTc-HYNIC-octreotide scan showed multiple axial and appendicular bone uptakes and paravertebral, abdominal, mediastinal, and
supraclavicular ganglionar uptakes. The 99mTc-HYNIC-octreotide showed much more lesion extension than the 131I-MIBG. Therefore, 99mTc-HYNIC-octreotide may be a promising radiopharmaceutical for the evaluation of neuroblastoma patients. This finding justifies
the pre liminary evaluation of this tracer in the context of a clinical trial. 相似文献
6.
Laitinen I Marjamäki P Någren K Laine VJ Wilson I Leppänen P Ylä-Herttuala S Roivainen A Knuuti J 《European journal of nuclear medicine and molecular imaging》2009,36(1):73-80
Purpose The ligand [11C]PK11195 binds with high affinity and selectivity to peripheral benzodiazepine receptor, expressed in high amounts in macrophages.
In humans, [11C]PK11195 has been used successfully for the in vivo imaging of inflammatory processes of brain tissue. The purpose of this
study was to explore the feasibility of [11C]PK11195 in imaging inflammation in the atherosclerotic plaques.
Methods The presence of PK11195 binding sites in the atherosclerotic plaques was verified by examining the in vitro binding of [3H]PK11195 onto mouse aortic sections. Uptake of intravenously administered [11C]PK11195 was studied ex vivo in excised tissue samples and aortic sections of a LDLR/ApoB48 atherosclerotic mice. Accumulation
of the tracer was compared between the atherosclerotic plaques and non-atherosclerotic arterial sites by autoradiography and
histological analyses.
Results The [3H]PK11195 was found to bind to both the atherosclerotic plaques and the healthy wall. The autoradiography analysis revealed
that the uptake of [11C]PK11195 to inflamed regions in plaques was more prominent (p = 0.011) than to non-inflamed plaque regions, but overall it was not higher than the uptake to the healthy vessel wall. Also,
the accumulation of 11C radioactivity into the aorta of the atherosclerotic mice was not increased compared to the healthy control mice.
Conclusions Our results indicate that the uptake of [11C]PK11195 is higher in inflamed atherosclerotic plaques containing a large number of inflammatory cells than in the non-inflamed
plaques. However, the tracer uptake to other structures of the artery wall was also prominent and may limit the use of [11C]PK11195 in clinical imaging of atherosclerotic plaques. 相似文献
7.
Masato Kobayashi Ichiro Matsunari Kodai Nishi Asuka Mizutani Yoshiharu Miyazaki Kazuhiro Ogai Jyunko Sugama Kazuhiro Shiba Keiichi Kawai Seigo Kinuya 《Annals of nuclear medicine》2016,30(4):263-271
Objective
Simultaneous acquisition of 99mTc and 123I was evaluated using a preclinical SPECT scanner with cadmium zinc telluride (CZT)-based detectors.Methods
10-ml cylindrical syringes contained about 37 MBq 99mTc-tetrofosmin (99mTc-TF) or 37 MBq 123I-15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (123I-BMIPP) were used to assess the relationship between these SPECT radioactive counts and radioactivity. Two 10-ml syringes contained 100 or 300 MBq 99mTc-TF and 100 MBq 123I-BMIPP to assess the influence of 99mTc upscatter and 123I downscatter, respectively. A rat-sized cylindrical phantom also contained both 100 or 300 MBq 99mTc-TF and 100 MBq 123I-BMIPP. The two 10-ml syringes and phantom were scanned using a pinhole collimator for rats. Myocardial infarction model rats were examined using 300 MBq 99mTc-TF and 100 MBq 123I-BMIPP. Two 1-ml syringes contained 105 MBq 99mTc-labeled hexamethylpropyleneamine oxime (99mTc-HMPAO) and 35 MBq 123I-labeled N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (123I-FP-CIT). The two 1-ml syringes were scanned using a pinhole collimator for mice. Normal mice were examined using 105 MBq 99mTc-HMPAO and 35 MBq 123I-FP-CIT.Results
The relationship between SPECT radioactive counts and radioactivity was excellent. Downscatter contamination of 123I-BMIPP exhibited fewer radioactive counts for 300 MBq 99mTc-TF without scatter correction (SC) in 125–150 keV. There was no upscatter contamination of 99mTc-TF in 150–175 keV. In the rat-sized phantom, the radioactive count ratio decreased to 4.0 % for 300 MBq 99mTc-TF without SC in 125–150 keV. In the rats, myocardial images and radioactive counts of 99mTc-TF with the dual tracer were identical to those of the 99mTc-TF single injection. Downscatter contamination of 123I-FP-CIT was 4.2 % without SC in 125–150 keV. In the first injection of 99mTc-HMPAO and second injection of 123I-FP-CIT, brain images and radioactive counts of 99mTc-HMPAO with the dual tracer in normal mice also were the similar to those of the 99mTc-HMPAO single injection. In the first injection of 123I-FP-CIT and second injection of 99mTc-HMPAO, the brain images and radioactive counts with the dual tracer were not much different from those of the 123I-FP-CIT single injection.Conclusions
Dual-tracer imaging of 99mTc- and 123I-labeled radiotracers is feasible in a preclinical SPECT scanner with CZT detector. When higher radioactivity of 99mTc-labeled radiotracers relative to 123I-labeled radiotracers is applied, correction methods are not necessarily required for the quantification of 99mTc- and 123I-labeled radiotracers when using a preclinical SPECT scanner with CZT detector.8.
Antenor-Dorsey JA Laforest R Moerlein SM Videen TO Perlmutter JS 《European journal of nuclear medicine and molecular imaging》2008,35(4):771-778
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. 相似文献
9.
Hatakeyama T Kawai N Nishiyama Y Yamamoto Y Sasakawa Y Ichikawa T Tamiya T 《European journal of nuclear medicine and molecular imaging》2008,35(11):2009-2017
Purpose The purpose of this prospective study was to clarify the individual and combined role of l-methyl-11C-methionine-positron emission tomography (MET-PET) and 3′-deoxy-3′-[18F]fluorothymidine (FLT)-PET in tumor detection, noninvasive grading, and assessment of the cellular proliferation rate in
newly diagnosed histologically verified gliomas of different grades.
Materials and methods Forty-one patients with newly diagnosed gliomas were investigated with MET-PET before surgery. Eighteen patients were also
examined with FLT-PET. MET and FLT uptakes were assessed by standardized uptake value of the tumor showing the maximum uptake
(SUVmax), and the ratio to uptake in the normal brain parenchyma (T/N ratio). All tumors were graded by the WHO grading system using surgical specimens, and the proliferation activity of the
tumors were determined by measuring the Ki-67 index obtained by immunohistochemical staining.
Results On semiquantitative analysis, MET exhibited a slightly higher sensitivity (87.8%) in tumor detection than FLT (83.3%), and
both tracers were 100% sensitive for malignant gliomas. Low-grade gliomas that were false negative on MET-PET also were false
negative on FLT-PET. Although the difference of MET SUVmax and T/N ratio between grades II and IV gliomas was statistically significant (P < 0.001), there was a significant overlap of MET uptake in the tumors. The difference of MET SUVmax and T/N ratio between grades II and III gliomas was not statistically significant. Low-grade gliomas with oligodendroglial components
had relatively high MET uptake. The difference of FLT SUVmax and T/N ratio between grades III and IV gliomas was statistically significant (P < 0.01). Again, the difference of FLT SUVmax and T/N ratio between grades II and III gliomas was not statistically significant. Grade III gliomas with non-contrast enhancement
on MR images had very low FLT uptake. In 18 patients who underwent PET examination with both tracers, a significant but relatively
weak correlation was observed between the individual SUVmax of MET and FLT (r = 0.54, P < 0.05) and T/N ratio of MET and FLT (r = 0.56, P < 0.05). Total FLT uptake in the tumor had a higher correlation (r = 0.89, P < 0.001) with Ki-67 proliferation index than MET uptake (r = 0.49, P < 0.01).
Conclusions PET studies using MET and FLT are useful for tumor detection in newly diagnosed gliomas. However, there is no complimentary
information in tumor detection with simultaneous measurements of MET- and FLT-PET in low grade gliomas. FLT-PET seems to be
superior than MET-PET in noninvasive tumor grading and assessment of proliferation activity in gliomas of different grades. 相似文献
10.
[<Superscript>18</Superscript>F]FLT-PET in oncology: current status and opportunities 总被引:8,自引:0,他引:8
Been LB Suurmeijer AJ Cobben DC Jager PL Hoekstra HJ Elsinga PH 《European journal of nuclear medicine and molecular imaging》2004,31(12):1659-1672
In recent years, [18F]-fluoro-3-deoxy-3-L-fluorothymidine ([18F]FLT) has been developed as a proliferation tracer. Imaging and measurement of proliferation with PET could provide us with a non-invasive staging tool and a tool to monitor the response to anticancer treatment. In this review, the basis of [18F]FLT as a proliferation tracer is discussed. Furthermore, an overview of the current status of [18F]FLT-PET research is given. The results of this research show that although [18F]FLT is a tracer that visualises cellular proliferation, it also has certain limitations. In comparison with the most widely used PET tracer, [18F]FDG, [18F]FLT uptake is lower in most cases. Furthermore, [18F]FLT uptake does not always reflect the tumour cell proliferation rate, for example during or shortly after certain chemotherapy regimens. The opportunities provided by, and the limitations of, [18F]FLT as a proliferation tracer are addressed in this review, and directions are given for further research, taking into account the strong and weak points of the new tracer. 相似文献
11.
I-Hsun Li Wen-Sheng Huang Chin-Bin Yeh Mei-Hsiu Liao Chia-Chieh Chen Lie-Hang Shen Jiang-Chuan Liu Kuo-Hsing Ma 《Nuclear medicine and biology》2009,36(6):605-611
IntroductionParkinson's disease (PD) affects both dopaminergic and serotonergic systems. In this study, we simultaneously evaluated dopamine and serotonin transporters in primates using dual-isotope single-photon emission computed tomography (SPECT) imaging and compared the results with traditional single-isotope imaging.MethodsFour healthy and one 6-OHDA-induced PD monkeys were used for this study. SPECT was performed over 4 h after individual or simultaneous injection of [99mTc]TRODAT-1 (a dopamine transporter imaging agent) and [123I]ADAM (a serotonin transporter imaging agent).ResultsThe results showed that the image quality and uptake ratios in different brain regions were comparable between single- and dual-isotope studies. The striatal [99mTc]TRODAT-1 uptake in the PD monkey was markedly lower than that in normal monkeys. The uptake of [123I]ADAM in the midbrain of the PD monkey was comparable to that in the normal monkeys, but there were decreased uptakes in the thalamus and striatum of the PD monkey.ConclusionsOur results suggest that dual-isotope SPECT using [99mTc]TRODAT-1 and [123I]ADAM can simultaneously evaluate changes in dopaminergic and serotonergic systems in a PD model. 相似文献
12.
Kotzerke J Linné C Meinhardt M Steinbach J Wirth M Baretton G Abolmaali N Beuthien-Baumann B 《European journal of nuclear medicine and molecular imaging》2007,34(6):884-888
Purpose The purpose of this study was to investigate the potential of [1-11C]acetate (AC) as a metabolic tracer for renal cell cancer in human subjects.
Methods Twenty-one patients with suspected kidney tumours were investigated with AC and dynamic PET. AC uptake was scored on a five-step
scale. Tumour localisation was known from CT/MRI. Histology was available in 18/21 patients. The results in these 18 patients
are reported.
Results AC uptake by the tumour was less than (n = 11), equal to (n = 5) or higher than (n = 2) uptake in the surrounding renal parenchyma. Histological tumour types showed a typical distribution, with a predominance
of clear cell carcinomas (n = 14) and only a small number of papillary cell carcinomas (n = 2) and oncocytomas (n = 2). Only the benign oncocytomas were highly positive with AC.
Conclusion In most kidney tumours the AC accumulation was not higher than in normal kidney parenchyma. Therefore, AC PET cannot be recommend
for the characterisation of a renal mass. 相似文献
13.
Ribeiro MJ Boddaert N Bellanné-Chantelot C Bourgeois S Valayannopoulos V Delzescaux T Jaubert F Nihoul-Fékété C Brunelle F De Lonlay P 《European journal of nuclear medicine and molecular imaging》2007,34(12):2120-2128
Purpose Neuroendocrine diseases are a heterogeneous group of entities with the ability to take up amine precursors, such as L-DOPA, and convert them into biogenic amines, such as dopamine. Congenital hyperinsulinism of infancy (HI) is a neuroendocrine
disease secondary to either focal adenomatous hyperplasia or a diffuse abnormal pancreatic insulin secretion. While focal
hyperinsulinism may be reversed by selective surgical resection, diffuse forms require near-total pancreatectomy when resistant
to medical treatment. Here, we report the diagnostic value of PET with [18F]fluoro-L-DOPA in distinguishing focal from diffuse HI.
Methods Forty-nine children were studied with [18F]fluoro-L-DOPA. A thoraco-abdominal scan was acquired 45–65 min after the injection of 4.2 ± 1.0 MBq/kg of [18F]fluoro-L-DOPA. Additionally, 12 of the 49 children were submitted to pancreatic venous catheterisation for blood samples (PVS) and
31 were also investigated using MRI.
Results We identified abnormal focal pancreatic uptake of [18F]fluoro-L-DOPA in 15 children, whereas diffuse radiotracer uptake was observed in the pancreatic area in the other 34 patients. In
children studied with both PET and PVS, the results were concordant in 11/12 cases. All patients with focal radiotracer uptake
and nine of the patients with diffuse pancreatic radiotracer accumulation, unresponsive to medical treatment, were submitted
to surgery. In 21 of these 24 patients, the histopathological results confirmed the PET findings. In focal forms, selective
surgery was followed by clinical remission without carbohydrate intolerance.
Conclusion These data demonstrate that PET with [18F]fluoro-L-DOPA is an accurate non-invasive technique allowing differential diagnosis between focal and diffuse forms of HI. 相似文献
14.
Kinuya S Li XF Yokoyama K Mori H Shiba K Watanabe N Shuke N Bunko H Michigishi T Tonami N 《European journal of nuclear medicine and molecular imaging》2003,30(11):1529-1531
Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of 99mTc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, 99mTc-tetrofosmin (TF), was also examined. Cellular uptake of 99mTc-MIBI and 99mTc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N2 and 5% CO2 reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function. 相似文献
15.
Takano A Gulyás B Varrone A Karlsson P Schou M Airaksinen AJ Vandenhende F Tauscher J Halldin C 《European journal of nuclear medicine and molecular imaging》2008,35(1):153-157
Introduction (S,S)-[18F]FMeNER-D2 is a recently developed positron emission tomography (PET) ligand for in vivo quantification of norepinephrine transporter.
A monkey occupancy study with the radioligand indicated that (S,S)-[18F]FMeNER-D2 can be useful for quantitative PET analysis. In this preliminary study, regional distributions in the living human brain
were evaluated.
Materials and methods Brain PET measurements were performed for a total of 255 min after the injection of 188.3 ± 5.7 MBq of (S,S)-[18F]FMeNER-D2 in four healthy male subjects. Regions of interests were drawn on the thalamus and the caudate in the coregistered MRI/PET
images.
Results (S,S)-[18F]FMeNER-D2 displayed good brain penetration and selective retention in regions rich in norepinephrine reuptake sites. The transient
peak equilibrium was reached during the PET measurements. The ratios of radioactivity uptake in the thalamus to that in the
caudate were 1.50 ± 0.06 for the time period of 90–255 min.
Conclusion The present preliminary investigation indicates that (S,S)-[18F]FMeNER-D2 has suitable characteristics for probing the norepinephrine reuptake system with PET in the human brain. 相似文献
16.
Christina Hultsch Margret Schottelius Jörg Auernheimer Andrea Alke Hans-Jürgen Wester 《European journal of nuclear medicine and molecular imaging》2009,36(9):1469-1474
Purpose Oxime formation between an aminooxy-functionalized peptide and an 18F-labelled aldehyde has recently been introduced as a powerful method for the rapid one-step chemoselective synthesis of radiofluorinated
peptides.
Materials and methods Here, the potential of using routinely produced and thus readily available [18F]fluorodeoxyglucose ([18F]FDG) as the aldehydic prosthetic group was investigated using an aminooxyacetyl-conjugated cyclic RGD peptide (cyclo(RGDfK(Aoa-(Boc))
as a model peptide.
Results The use of [18F]FDG from routine production ([18F]FDGTUM) containing an excess of d-glucose did not allow the radiosynthesis of [18F]FDG-RGD in activities >37 MBq in reasonable yield, rendering the direct use of clinical grade [18F]FDG for the routine clinical synthesis of 18F-labelled peptides impossible. Using no-carrier-added (n.c.a.) [18F]FDG obtained via HPLC separation of [18F]FDGTUM from excess glucose, however, afforded [18F]FDG-RGD in yields of 56–93% (decay corrected) and activities up to 37 MBq. Suitable reaction conditions were 20 min at 120°C
and pH 2.5, and a peptide concentration of 5 mM. In a preliminary in vivo biodistribution study in M21 melanoma-bearing nude mice, [18F]FDG-RGD showed increased tumour accumulation compared to the “gold standard” [18F]galacto-RGD (2.18 vs 1.49 %iD/g, respectively, at 120 min after injection), but also slightly increased uptake in non-target
organs, leading to comparable tumour/organ ratios for both compounds.
Conclusion These data demonstrate that chemoselective 18F-labelling of aminooxy-functionalized peptides using n.c.a. [18F]FDG represents a radiofluorination/glycosylation strategy that allows preparation of 18F-labelled peptides in high yield with suitable pharmacokinetics. As soon as the necessary n.c.a. preparation of [18F]FDG prior to reaction with the Aoa-peptide can be implemented in a fully automated [18F]FDG-synthesis, [18F]fluoroglucosylation of peptides may represent a promising alternative to currently used chemoselective one-step 18F-labelling protocols. 相似文献
17.
Reske SN Blumstein NM Glatting G 《European journal of nuclear medicine and molecular imaging》2008,35(1):9-17
Purpose The aim of this study was to assess the accuracy and clinical impact of [11C]choline PET/CT for localizing occult relapse of prostate adenocarcinoma after radical prostatectomy.
Methods Fourty-nine patients with prostate adenocarcinoma, radical prostatectomy, no evidence of metastatic disease, and occult relapse
underwent [11C]choline PET/CT. Thirty-six of the patients had biochemical evidence and histological evaluation of local recurrence. Thirteen
patients had PSA < 0.3 ng/ml and no evidence of active disease after 1 year follow-up. Focal nodular [11C]choline uptake in the prostatic fossa was visually assessed and graded on a five point scale. Maximum standardized radioactivity
uptake value (SUVmax) and the lesion size were measured. A receiver operating characteristic (ROC) analysis was performed and the clinical impact
of the PET/CT study was determined.
Results [11C]choline PET/CT was true positive in 23/33 patients and true negative in 12/13 controls. SUVmax of local recurrence was 3.0 (median, range 0.6–7.4) and 1.1 (0.4–1.6) in controls (p = 0.0002). Lesion size was 1.7 cm (range 0.9–3.7). Area under the ROC curve for detecting relapse was 0.90 ± 0.05 and 0.83 ± 0.06
for visual evaluation and SUVmax, respectively. Sensitivity and specificity of [11C]choline PET/CT were 0.73 and 0.88, respectively. [11C]choline PET/CT identified 12/17 (71%) patients with a favourable biochemical response to local radiotherapy at 2 year (median,
0.8–3.2 range) follow-up.
Conclusions Focally increased [11C]choline uptake in the prostatic bed reliably predicted local low volume occult relapsing prostate adenocarcinoma after radical
prostatectomy and identified 71% of patients with a favourable biochemical response to local radiotherapy. 相似文献
18.
Rolleman EJ Forrer F Bernard B Bijster M Vermeij M Valkema R Krenning EP de Jong M 《European journal of nuclear medicine and molecular imaging》2007,34(5):763-771
Purpose In peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, the kidneys are the major dose-limiting
organs, because of tubular reabsorption and retention of radioactivity. Preventing renal uptake or toxicity will allow for
higher tumour radiation doses. We tested the cytoprotective drug amifostine, which selectively protects healthy tissue during
chemo- and radiotherapy, for its renoprotective capacities after PRRT with high-dose [177Lu-DOTA0,Tyr3]octreotate.
Methods Male Lewis rats were injected with 278 or 555 MBq [177Lu-DOTA0,Tyr3]octreotate to create renal damage and were followed up for 130 days. For renoprotection, rats received either amifostine
or co-injection with lysine. Kidneys, blood and urine were collected for toxicity measurements. At 130 days after PRRT, a
single-photon emission computed tomography (SPECT) scan was performed to quantify tubular uptake of 99mTc-dimercaptosuccinic acid (DMSA), a measure of tubular function.
Results Treatment with 555 MBq [177Lu-DOTA0,Tyr3]octreotate resulted in body weight loss, elevated creatinine and proteinuria. Amifostine and lysine treatment significantly
prevented this rise in creatinine and the level of proteinuria, but did not improve the histological damage. In contrast,
after 278 MBq [177Lu-DOTA0,Tyr3]octreotate, creatinine values were slightly, but not significantly, elevated compared with the control rats. Proteinuria
and histological damage were different from controls and were significantly improved by amifostine treatment. Quantification
of 99mTc-DMSA SPECT scintigrams at 130 days after [177Lu-DOTA0,Tyr3]octreotate therapy correlated well with 1/creatinine (r
2 = 0.772, p < 0.001).
Conclusion Amifostine and lysine effectively decreased functional renal damage caused by high-dose [177Lu-DOTA0,Tyr3]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well as to maximise anti-tumour efficacy. 相似文献
19.
Kameyama R Yamamoto Y Izuishi K Takebayashi R Hagiike M Murota M Kaji M Haba R Nishiyama Y 《European journal of nuclear medicine and molecular imaging》2009,36(3):382-388
Purpose We prospectively investigated the feasibility of 3′-deoxy-3′-18F-fluorothymidine (FLT) positron emission tomography (PET) for the detection of gastric cancer, in comparison with 2-deoxy-2-18F-fluoro-d-glucose (FDG) PET, and determined the degree of correlation between the two radiotracers and proliferative activity as indicated
by Ki-67 index.
Methods A total of 21 patients with newly diagnosed advanced gastric cancer were examined with FLT PET and FDG PET. Tumour lesions
were identified as areas of focally increased uptake, exceeding that of surrounding normal tissue. For semiquantitative analysis,
the maximal standardized uptake value (SUV) was calculated.
Results For detection of advanced gastric cancer, the sensitivities of FLT PET and FDG PET were 95.2% and 95.0%, respectively. The
mean (±SD) SUV for FLT (7.0 ± 3.3) was significantly lower than that for FDG (9.4 ± 6.3 p < 0.05). The mean FLT SUV and FDG SUV in nonintestinal tumours were higher than in intestinal tumours, although the difference
was not statistically significant. The mean (±SD) FLT SUV in poorly differentiated tumours (8.5 ± 3.5) was significantly higher
than that in well and moderately differentiated tumours (5.3 ± 2.1; p < 0.04). The mean FDG SUV in poorly differentiated tumours was higher than in well and moderately differentiated tumours,
although the difference was not statistically significant. There was no significant correlation between Ki-67 index and either
FLT SUV or FDG SUV.
Conclusion FLT PET showed as high a sensitivity as FDG PET for the detection of gastric cancer, although uptake of FLT in gastric cancer
was significantly lower than that of FDG. 相似文献
20.
Ko BH Paik JY Jung KH Bae JS Lee EJ Choe YS Kim BT Lee KH 《European journal of nuclear medicine and molecular imaging》2008,35(3):554-561
Objectives Small animal imaging with meta-iodobenzylguanidine (MIBG) allows characterization of animal models, optimization of tumor
treatment strategies, and monitoring of gene expression. Anesthetic agents, however, can affect norepinephrine (NE) transport
and systemic sympathetic activity. We thus elucidated the effects of anesthetic agents on MIBG transport and biodistribution.
Methods SK-N-SH neuroblastoma and PC-12 pheochromocytoma cells were measured for 123I-MIBG uptake after treatment with ketamine (Ke), xylazine (Xy), Ke/Xy, or pentobarbital (Pb). NE transporters were assessed
by Western blots. Normal ICR mice and PC-12 tumor-bearing mice were injected with 123I-MIBG 10 min after anesthesia with Ke/Xy, Ke, Xy, or Pb. Plasma NE levels and MIBG biodistribution were assessed.
Results Cellular 123I-MIBG uptake was dose-dependently inhibited by Ke and Xy but not by Pb. Treatment for 2 h with 300 μM Ke, Xy, and Ke/Xy decreased
uptake to 46.0 ± 1.6, 24.8 ± 1.5, and 18.3 ± 1.6% of controls. This effect was completely reversed by fresh media, and there
was no change in NE transporter levels. In contrast, mice anesthetized with Ke/Xy showed no decrease of MIBG uptake in target
organs. Instead, uptakes and organ-to-blood ratios were increased in the heart, lung, liver, and adrenals. Plasma NE was notably
reduced in the animals with corresponding decreases in blood MIBG, which partly contributed to the increase in target organ
uptake.
Conclusion In spite of their inhibitory effect at the transporter level, Ke/Xy anesthesia is a satisfactory method for MIBG imaging that
allows favorable target tissue uptake and contrast by reducing circulating NE and MIBG.
Bong-Ho Ko and Jin-Young Paik equally contributed to this work.
This work was supported by the Korea Research Foundation Grant KRF-2005-202-E00116.
Presented in part at the fifth Annual Meeting of the Society for Molecular Imaging, Hawaii, August 30–September 2, 2006. 相似文献