Clinical Performance Comparison of a Long Versus a Short Axial Field-of-View PET/CT Using EARL-Compliant Reconstructions.

PURPOSE: To ensure comparable PET/CT image quality between or within centres, clinical inter-system performance comparisons following European Association of Nuclear Medicine Research Ltd. (EARL) guidelines is required. In this work the performance of the long axial field-of-view Biograph Vision Quadra is compared to its predecessor, the short axial field-of-view Biograph Vision. PROCEDURES: To this aim, patients with suspected tumour lesions received a single weight-based (3 MBq/kg) 2-deoxy-2-[18F]fluoro-D-glucose injection and underwent routine clinical ( ∼ 15 min) scans on the Vision and 3-min scans on the Quadra in listmode in balanced order. Image quality (IQ), image noise (IN), and tumour demarcation (TD) were assessed visually by four nuclear medicine physicians using a 5-point Likert scale and semiquantitative analysis was performed using standardised uptake values (SUVs). Inter-reader agreement was tested using Wilcoxon's signed rank test and the SUVs were statistically compared using a paired t-test. RESULTS: Twenty patients (mean age, 60 years ± 8.8 [standard deviation], 16 male) were enrolled. Inter-reader agreement ranged from good to very good for IQ and IN (0.62 ≤ W ≤ 0.81), and fair for TD (0.29 ≤ W ≤ 0.39). Furthermore, a significant difference was found for TD (p = 0.015) between the systems, showing improved TD for the Quadra. CONCLUSION: This study demonstrates that the Quadra can be used in routine clinical practice with multiple PET/CT systems or in multicentre studies. This system provides comparable diagnostic image quality and semiquantitative accuracy, improved TD, and has the advantage of shorter scan durations.

Pharmacokinetic Analysis of [18F]FES PET in the Human Brain and Pituitary Gland.

PURPOSE: Estrogen receptors (ER) are implicated in psychiatric disorders. We assessed if ER availability in the human brain could be quantified using 16α-[18F]-fluoro-17ß-estradiol ([18F]FES) positron emission tomography (PET). PROCEDURES: Seven post­menopausal women underwent a dynamic [18F]FES PET scan with arterial blood sampling. A T1-weighted MRI was acquired for anatomical information. After one week, four subjects received a selective ER degrader (SERD), four hours before the PET scan. Pharmacokinetic analysis was performed using a metabolite-corrected plasma curve as the input function. The optimal kinetic model was selected based on the Akaike information criterion and standard error of estimated parameters. Accuracy of Logan graphical analysis and standardized uptake value (SUV) was determined via correlational analyses. RESULTS: The reversible two-tissue compartment model (2T4k) model with fixed K1/k2 was preferred. The total volume of distribution (VT) could be more reliably estimated than the binding potential (BPND). A high correlation of VT with Logan graphical analysis was observed, but only a moderate correlation with SUV. SERD administration resulted in a reduced VT in the pituitary gland, but not in other regions. CONCLUSIONS: The optimal quantification method for [18F]FES was the 2T4k with fixed K1/k2 or Logan graphical analysis, but specific binding was only observed in the pituitary gland.

Current and Future Use of Long Axial Field-of-View Positron Emission Tomography/Computed Tomography Scanners in Clinical Oncology.

The latest technical development in the field of positron emission tomography/computed tomography (PET/CT) imaging has been the extension of the PET axial field-of-view. As a result of the increased number of detectors, the long axial field-of-view (LAFOV) PET systems are not only characterized by a larger anatomical coverage but also by a substantially improved sensitivity, compared with conventional short axial field-of-view PET systems. In clinical practice, this innovation has led to the following optimization: (1) improved overall image quality, (2) decreased duration of PET examinations, (3) decreased amount of radioactivity administered to the patient, or (4) a combination of any of the above. In this review, novel applications of LAFOV PET in oncology are highlighted and future directions are discussed.

Impact of an Adenosine A2A Receptor Agonist and Antagonist on Binding of the Dopamine D2 Receptor Ligand [11C]raclopride in the Rodent Striatum.

Adenosine A2A and dopamine D2 receptors in the basal ganglia form heterotetrameric structures that are involved in the regulation of motor activity and neuropsychiatric functions. The present study examines the A2A receptor-mediated modulation of D2 receptor binding in vivo using positron emission tomography (PET) with the D2 antagonist tracer [11C]raclopride. Healthy male Wistar rats (n = 8) were scanned (60 min dynamic scan) with [11C]raclopride at baseline and 7 days later following an acute administration of the A2A agonist CGS21680 (1 mg/kg), using a MicroPET Focus-220 camera. Nondisplaceable binding potential (BPND) values were calculated using a simplified reference tissue model (SRTM), with cerebellum as the reference tissue. SRTM analysis did not show any significant changes in [11C]raclopride BPND (p = 0.102) in striatum after CGS21680 administration compared to the baseline. As CGS21680 strongly affects hemodynamics, we also used arterial blood sampling and a metabolite-corrected plasma input function for compartment modeling using the reversible two-tissue compartment model (2TCM) to obtain the BPND from the k3/k4 ratio and from the striatum/cerebellum volume of distribution ratio (DVR) in a second group of animals. These rats underwent dynamic [11C]raclopride scans after pretreatment with a vehicle (n = 5), a single dose of CGS21680 (1 mg/kg, n = 5), or a single dose of the A2A antagonist KW6002 (1 mg/kg, n = 5). The parent fraction in plasma was significantly higher in the CGS21680-treated group (p = 0.0001) compared to the vehicle-treated group. GCS21680 administration significantly reduced the striatal k3/k4 ratio (p < 0.01), but k3 and k4 estimates may be less reliable. The BPND (DVR-1) decreased from 1.963 ± 0.27 in the vehicle-treated group to 1.53 ± 0.55 (p = 0.080) or 1.961 ± 0.11 (p = 0.993) after the administration of CGS21680 or KW6002, respectively. Our study suggests that the A2A agonist CGS21680, but not the antagonist KW6002, may reduce the D2 receptor availability in the striatum.

Analyzing the Estrogen Receptor Status of Liver Metastases with [18F]-FES-PET in Patients with Breast Cancer.

BACKGROUND: Positron emission tomography (PET) with 16α-[18F]-fluoro-17ß-estradiol ([18F]-FES) can visualize estrogen receptor (ER) expression, but it is challenging to determine the ER status of liver metastases, due to high physiological [18F]-FES uptake. We evaluated whether [18F]-FES-PET can be used to determine the ER status of liver metastases, using corresponding liver biopsies as the gold standard. METHODS: Patients with metastatic breast cancer (n = 23) were included if they had undergone a [18F]-FES-PET, liver metastasis biopsy, CT-scan, and [18F]-FDG-PET. [18F]-FES-PET scans were assessed by visual and quantitative analysis, tracer uptake was correlated with ER expression measured by immunohistochemical staining and the effects of region-of-interest size and background correction were determined. RESULTS: Visual analysis allowed ER assessment of liver metastases with 100% specificity and 18% sensitivity. Quantitative analysis improved the sensitivity. Reduction of the region-of-interest size did not further improve the results, but background correction improved ER assessment, resulting in 83% specificity and 77% sensitivity. Using separate thresholds for ER+ and ER- metastases, positive and negative predictive values of 100% and 75%, respectively, could be obtained, although 30% of metastases remained inconclusive. CONCLUSION: In the majority of liver metastases, ER status can be determined with [18F]-FES-PET if background correction and separate thresholds are applied.

In Vivo Quantification of ERß Expression by Pharmacokinetic Modeling: Studies with 18F-FHNP PET.

The estrogen receptor (ER) is a target for endocrine therapy in breast cancer patients. Individual quantification of ERα and ERß expression, rather than total ER levels, might enable better prediction of the response to treatment. We recently developed the tracer 2-18F-fluoro-6-(6-hydroxynaphthalen-2-yl)pyridin-3-ol (18F-FHNP) for assessment of ERß levels with PET. In the current study, we investigated several pharmacokinetic analysis methods to quantify changes in ERß availability with 18F-FHNP PET. Methods: Male nude rats were subcutaneously inoculated in the shoulder with ERα/ERß-expressing SKOV3 human ovarian cancer cells. Two weeks after tumor inoculation, a dynamic 18F-FHNP PET scan with arterial blood sampling was acquired from rats treated with vehicle or various concentrations of estradiol (nonspecific ER agonist) or genistein (ERß-selective agonist). Different pharmacokinetic models were applied to quantify ERß availability in the tumor. Results: Irreversible-uptake compartmental models fitted the kinetics of 18F-FHNP uptake better than reversible models. The irreversible 3-tissue-compartment model, which included both the parent and the metabolite input function, gave results comparable to those of the irreversible 2-tissue-compartment model with only a parent input function, indicating that radioactive metabolites contributed little to the tumor uptake. Patlak graphical analysis gave metabolic rates (Ki, the irreversible uptake rate constant) comparable to compartment modeling. The Ki values correlated well with ERß expression but not with ERα, confirming that Ki is a suitable parameter to quantify ERß expression. SUVs at 60 min after tracer injection also correlated (r2 = 0.47; P = 0.04) with ERß expression. A reduction in 18F-FHNP tumor uptake and Ki values was observed in the presence of estradiol or genistein. Conclusion:18F-FHNP PET enables assessment of ERß availability in tumor-bearing rats. The most suitable parameter to quantify ERß expression is the Ki However, a simplified static imaging protocol for determining the SUVs can be applied to assess ERß levels.

Quantification, improvement, and harmonization of small lesion detection with state-of-the-art PET.

In recent years, there have been multiple advances in positron emission tomography/computed tomography (PET/CT) that improve cancer imaging. The present generation of PET/CT scanners introduces new hardware, software, and acquisition methods. This review describes these new developments, which include time-of-flight (TOF), point-spread-function (PSF), maximum-a-posteriori (MAP) based reconstruction, smaller voxels, respiratory gating, metal artefact reduction, and administration of quadratic weight-dependent 18F-fluorodeoxyglucose (FDG) activity. Also, hardware developments such as continuous bed motion (CBM), (digital) solid-state photodetectors and combined PET and magnetic resonance (MR) systems are explained. These novel techniques have a significant impact on cancer imaging, as they result in better image quality, improved small lesion detectability, and more accurate quantification of radiopharmaceutical uptake. This influences cancer diagnosis and staging, as well as therapy response monitoring and radiotherapy planning. Finally, the possible impact of these developments on the European Association of Nuclear Medicine (EANM) guidelines and EANM Research Ltd. (EARL) accreditation for FDG-PET/CT tumor imaging is discussed.

PET imaging of tumor hypoxia using 18F-fluoroazomycin arabinoside in stage III-IV non-small cell lung cancer patients.

UNLABELLED: Tumor hypoxia hampers the efficacy of radiotherapy because of its increased resistance to ionizing radiation. The aim of the present study was to estimate the potential added clinical value of the specific hypoxia tracer (18)F-fluoroazomycin arabinoside ((18)F-FAZA) over commonly used (18)F-FDG in the treatment of advanced-stage non-small cell lung cancer (NSCLC). METHODS: Eleven patients with stage III or stage IV NSCLC underwent (18)F-FDG and (18)F-FAZA PET before chemoradiotherapy. The maximum standardized uptake value (SUVmax) was used to depict (18)F-FDG uptake, and the tumor-to-background (T/B) ratio and tumor fractional hypoxic volume (FHV) were used to quantify hypoxia. The spatial correlation between (18)F-FDG and (18)F-FAZA uptake values was investigated using voxel-based analysis. Partial-volume correction was applied. RESULTS: All 11 patients showed clear uptake of (18)F-FAZA in the primary tumor. However, different patterns of (18)F-FDG and (18)F-FAZA uptake distributions were observed and varied widely among different tumors. No significant correlation was observed between (18)F-FDG SUVmax and (18)F-FAZA T/B ratio (P = 0.055). The median FHV of 1.4 was 48.4% (range, 5.0-91.5). A significant positive correlation was found between the (18)F-FAZA T/B ratio and FHV of 1.4 (P < 0.001). There was no correlation between the lesion size and FHV or between the (18)F-FDG SUVmax and FHV. The pattern of tumoral (18)F-FDG uptake was rather homogeneous, whereas (18)F-FAZA uptake was more heterogeneous, suggesting that (18)F-FAZA identifies hypoxic areas within metabolically active areas of tumor. A significant correlation between (18)F-FDG SUVmax and lesion size (P = 0.002) was observed. CONCLUSION: (18)F-FAZA PET imaging is able to detect heterogeneous distributions of hypoxic subvolumes out of homogeneous (18)F-FDG background in a clinical setting. Therefore, (18)F-FAZA might be considered a tool for guiding dose escalation to the hypoxic fraction of the tumor.

Induction of ß-glucuronidase release by cytostatic agents in small tumors.

Extracellular ß-glucuronidase (ß-GUS) in tumors has been investigated as a target enzyme for prodrug therapy. However, despite encouraging preclinical results, animal studies also indicate that the success of prodrug therapy might be limited by the insufficient prodrug-converting enzyme activity, especially in small tumors. We hypothesized that a single dose of a cytostatic drug might induce the release of ß-GUS in small tumors, resulting in increased levels of extracellular ß-GUS and consequently a higher efficacy of the prodrug treatment. Here we examine the extent of ß-GUS release in small C6 glioma tumors after a single treatment of doxorubicin (DOX), carmustine (BCNU) and tumor necrosis factor α (TNF-α) with positron emission tomography (PET) and the tracer 1-O-(4-(2-fluoroethyl-carbamoyloxymethyl)-2-nitrophenyl)-O-ß-d-glucopyronuronate, [(18)F]FEAnGA, which has been proven to be selective for extracellular ß-GUS. Induction of ß-GUS release was first investigated in cultured C6 glioma cells. In addition, a [(18)F]FEAnGA PET study was performed in C6 tumor-bearing rats 48 h after a single treatment with different cytostatics to evaluate the extent of ß-glucuronidase release. The cleavage of [(18)F]FEAnGA by ß-GUS was analyzed in tumor homogenates. The induction of tumor necrosis and leukocyte infiltration was confirmed by histochemical analysis and flow cytometry. The in vitro studies indicated that all treatments resulted in a decline of viable cells and an increase of extracellular ß-GUS activity. PET studies confirmed that ß-GUS was released in vivo and the distribution volume of the PET tracer [(18)F]FEAnGA in C6 gliomas was increased significantly by 15-70%, depending on the treatment. Histochemical analysis of the tumors indicated that carmustine and TNF-α treatment caused a larger necrotic area with the absence of infiltrating immune cells, whereas doxorubicin induced an increase in leukocyte infiltration. These results were confirmed by flow cytometry. In conclusion, the present study demonstrates that a single dose of a cytostatic agent is able to increase the release of ß-GUS. The release in ß-GUS can be monitored by [(18)F]FEAnGA PET in a noninvasive manner. This study may open the way to a two-step chemotherapy-prodrug approach, in which tumors are treated with a single dose of a cytostatic drug prior to prodrug treatment.

In vivo evaluation of 1-O-(4-(2-fluoroethyl-carbamoyloxymethyl)-2-nitrophenyl)-O-ß-D-glucopyronuronate: a positron emission tomographic tracer for imaging ß-glucuronidase activity in a tumor/inflammation rodent model.

ß-Glucuronidase (ß-GUS) plays an important role in inflammation and degenerative processes. The enzyme has also been investigated as a target in prodrug therapy for cancer. To investigate the role of ß-GUS in pathologies and to optimize ß-GUS-based prodrug therapies, we recently developed a positron emission tomographic (PET) tracer, 1-O-(4-(2-fluoroethyl-carbamoyloxymethyl)-2-nitrophenyl)-O-ß-D-glucopyronuronate ([18F]FEAnGA), which proved to be selectively cleaved by ß-GUS. Here we present the in vivo evaluation of [18F]FEAnGA for imaging of ß-GUS in a tumor/inflammation model. Ex vivo biodistribution of [18F]FEAnGA was conducted in healthy rats. PET imaging and pharmacokinetic modeling were performed in Wistar rats bearing C6 tumors of different sizes and sterile inflammation. The biodistribution studies of [18F]FEAnGA indicated low uptake in major organs and rapid excretion through the renal pathway. MicroPET studies revealed three times higher uptake in the viable part of larger C6 gliomas than in smaller C6 gliomas. Uptake in inflamed muscle was significantly higher than in control muscle. The distribution volume of [18F]FEAnGA in the viable part of the tumor correlated well with the cleavage of the tracer to [18F]fluoroethylamine and the spacer 4-hydroxy-3-nitrobenzyl alcohol. [18F]FEAnGA is a PET tracer able to detect increased activity of ß-GUS in large solid tumors and in inflamed tissues.

In vivo evaluation of [18F]FEAnGA-Me: a PET tracer for imaging ß-glucuronidase (ß-GUS) activity in a tumor/inflammation rodent model.

INTRODUCTION: The PET tracer, 1-O-(4-(2-fluoroethyl-carbamoyloxymethyl)-2-nitrophenyl)-O-ß-d-glucopyronuronate ([(18)F]FEAnGA), was recently developed for PET imaging of extracellular ß-glucuronidase (ß-GUS). However, [(18)F]FEAnGA exhibited rapid renal clearance, which resulted in a relatively low tracer uptake in the tumor. To improve the pharmacokinetics of [(18)F]FEAnGA, we developed its more lipophilic methyl ester analog, [(18)F]FEAnGA-Me. METHODS: [(18)F]FEAnGA-Me was obtained by alkylation of the O-protected glucuronide methyl ester precursor with [(18)F]-fluoroethylamine ([(18)F]FEA), followed by removal of the acetate protecting groups with NaOMe/MeOH. The PET tracer was evaluated by in vitro and in vivo studies. RESULTS: [(18)F]FEAnGA-Me was obtained in 5%-10% overall radiochemical yield. It is 10-fold less hydrophilic than [(18)F]FEAnGA and it is stable in PBS and in the presence of ß-GUS for 1 h. However, in the presence of esterase or plasma [(18)F]FEAnGA-Me is converted to [(18)F]FEAnGA, and subsequently converted to [(18)F]FEA by ß-GUS. MicroPET studies in Wistar rats bearing a C6 glioma and a sterile inflammation showed similar uptake in tumors after injection of either [(18)F]FEAnGA-Me or [(18)F]FEAnGA. Both tracers had a rapid two-phase clearance of total plasma radioactivity with a half-life of 1 and 8 min. The [(18)F]FEAnGA fraction generated from [(18)F]FEAnGA-Me by in vivo hydrolysis had a circulation half-life of 1 and 11 min in plasma. Similar distribution volume in the viable part of the tumor was found after injection of either [(18)F]FEAnGA-Me or [(18)F]FEAnGA. CONCLUSION: The imaging properties of [(18)F]FEAnGA-Me were not significantly better than those of [(18)F]FEAnGA. Therefore, other strategies should be applied in order to improve the kinetics of these tracers.

Small-animal PET study of adenosine A(1) receptors in rat brain: blocking receptors and raising extracellular adenosine.

UNLABELLED: Activation of adenosine A(1) receptors (A(1)R) in the brain causes sedation, reduces anxiety, inhibits seizures, and promotes neuroprotection. Cerebral A(1)R can be visualized using 8-dicyclopropylmethyl-1-(11)C-methyl-3-propyl-xanthine ((11)C-MPDX) and PET. This study aims to test whether (11)C-MPDX can be used for quantitative studies of cerebral A(1)R in rodents. METHODS: (11)C-MPDX was injected (intravenously) into isoflurane-anesthetized male Wistar rats (300 g). A dynamic scan of the central nervous system was obtained, using a small-animal PET camera. A cannula in a femoral artery was used for blood sampling. Three groups of animals were studied: group 1, controls (saline-treated); group 2, animals pretreated with the A(1)R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 mg, intraperitoneally); and group 3, animals pretreated (intraperitoneally) with a 20% solution of ethanol in saline (2 mL) plus the adenosine kinase inhibitor 4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido[2,3-d] pyrimidine dihydrochloride (ABT-702) (1 mg). DPCPX is known to occupy cerebral A(1)R, whereas ethanol and ABT-702 increase extracellular adenosine. RESULTS: In groups 1 and 3, the brain was clearly visualized. High uptake of (11)C-MPDX was noted in striatum, hippocampus, and cerebellum. In group 2, tracer uptake was strongly suppressed and regional differences were abolished. The treatment of group 3 resulted in an unexpected 40%-45% increase of the cerebral uptake of radioactivity as indicated by increases of PET standardized uptake value, distribution volume from Logan plot, nondisplaceable binding potential from 2-tissue-compartment model fit, and standardized uptake value from a biodistribution study performed after the PET scan. The partition coefficient of the tracer (K(1)/k(2) from the model fit) was not altered under the study conditions. CONCLUSION: (11)C-MPDX shows a regional distribution in rat brain consistent with binding to A(1)R. Tracer binding is blocked by the selective A(1)R antagonist DPCPX. Pretreatment of animals with ethanol and adenosine kinase inhibitor increases (11)C-MPDX uptake. This increase may reflect an increased availability of A(1)R after acute exposure to ethanol.

New positron emission tomography tracer [(11)C]carvedilol reveals P-glycoprotein modulation kinetics.

Imaging of P-glycoprotein (P-gp) function in the blood-brain barrier (BBB) may support development of strategies, which will improve drug delivery to the brain. [(11)C]verapamil has been developed as a positron emission tomography (PET) tracer, to image P-gp function in vivo. Ideally, for the purpose of brain imaging, tracers should have a log P between 0.9 and 2.5. The beta-receptor antagonist carvedilol is a P-gp substrate with a log P=2.0, and can be labeled with [(11)C]. The aim of this study was to determine whether the P-gp substrate [(11)C]carvedilol can be used as a PET tracer for visualisation and quantification of the P-gp function in the BBB. Cellular [(11)C]carvedilol accumulation in GLC(4), GLC(4)/P-gp, and GLC(4)/Adr cells increased three-fold in the GLC(4)/P-gp cells after pretreatment with cyclosporin A (CsA) whereas no effect of MK571 could be determined in the GLC(4)/Adr cells. Ex vivo [(11)C]carvedilol biodistribution studies showed that [(11)C]carvedilol uptake in the brain was increased by CsA. [(11)C]carvedilol uptake in other organs was not affected by CsA. Autoradiography studies of rat brains showed that [(11)C]carvedilol was homogeneously distributed over the brain and that pretreatment with CsA increased [(11)C]carvedilol uptake. In vivo PET experiments were performed with and without P-gp modulation by CsA. P-gp mediated transport was quantified by Logan analysis of the PET data, calculating the distribution volume (DV) of [(11)C]carvedilol in the brain. Logan analysis resulted in excellent fits, revealing that [(11)C]carvedilol is not trapped in the brain. Brain DV of [(11)C]carvedilol showed a dose-dependent increase of maximal three-fold after CsA pretreatment. Above 15 mg kg(-1), no change in DV was found. Compared to [(11)C]verapamil less CsA was needed to reach maximal DV, suggesting that [(11)C]carvedilol kinetics is a more sensitive tool to in vivo measure P-gp function.

PET for evaluation of differential myocardial perfusion dynamics after VEGF gene therapy and laser therapy in end-stage coronary artery disease.

UNLABELLED: The purpose of this study was to appraise the value of PET in the assessment of the effect of supposedly proangiogenic new therapies such as gene therapy with vascular endothelial growth factor (VEGF) gene and endomyocardial laser therapy. METHODS: Thirty-five patients with end-stage coronary artery disease and class III (Canadian Cardiovascular Society) angina were included. Myocardial ischemia was evaluated with dipyridamole PET scanning and exercise tolerance with bicycle ergometry. Ten patients were treated with naked plasmid DNA encoding for human VEGF165 (VEGF) and 12 patients were treated with laser therapy (direct myocardial revascularization [DMR]) using an electromechanical mapping system. Thirteen patients were treated with standard medical therapy (control). RESULTS: In both active treatment groups, angina was reduced in most subjects, except in 2 VEGF and 5 DMR patients. In the control group, no improvement in anginal classification was found, except in 3 subjects. On the PET scan, solely in the VEGF group, the stress perfusion was significantly improved (from 57 +/- 33 to 81 +/- 55 mL/min/100 g; P = 0.031). Furthermore, in the VEGF group, the number of ischemic segments was reduced from 274 +/- 41 to 234 +/- 48 segments (P = 0.004) but not in the DMR group (from 209 +/- 43 to 215 +/- 52 segments) or in the control group (from 218 +/- 18 to 213 +/- 28 segments). Bicycle exercise duration showed slight nonsignificant changes in the VEGF group (from 3.6 +/- 2.0 to 4.6 +/- 2.1 min), in the DMR group (from 5.1 +/- 1.5 to 4.7 +/- 1.3 min), and in the control group (from 3.3 +/- 1.8 to 3.5 +/- 2.3 min). CONCLUSION: PET showed that intramyocardial gene therapy with the human VEGF165 gene in contrast to laser DMR treatment effectively reduces myocardial ischemia.

Evaluation of [18F]FHPG as PET tracer for HSVtk gene expression.

In rats, the relationship between [(18)F]FHPG accumulation and HSVtk expression was studied with PET and autoradiography. [(18)F]FHPG distribution closely corresponded with HSVtk immunohistochemical staining. ROI analysis of tracer uptake 2 hours p.i. and Patlak graphical analysis were applied to quantify the PET data. For both analysis methods, the [(18)F]FHPG PET signal correlated well with the fraction of HSVtk expressing cells implanted, but showed a plateau when plotted against HSVtk protein levels. This might be due to rate limiting [(18)F]FHPG membrane transport.

L-1-11C-tyrosine PET in patients with laryngeal carcinomas: comparison of standardized uptake value and protein synthesis rate.

UNLABELLED: PET with L-1-(11)C-tyrosine (TYR) can measure and quantify increased protein synthesis in tumor tissue in vivo. For quantification of the protein synthesis rate (PSR), arterial cannulation with repeated blood sampling to obtain the plasma input function and a dynamic TYR PET study to calculate a time-activity curve are necessary. In most PET studies the standardized uptake value (SUV) method is used to quantify tumor activity. The SUV can be calculated without repeated arterial blood sampling and prolonged scanning time, as required for determination of the PSR. The relationship between PSR and SUV is largely unknown and different factors can cause wide variability in the SUV. Therefore, the comparison of the absolute quantification method (PSR) with the SUV method is obligatory to determine the possible use of noninvasive PET in head and neck oncology. METHODS: Twenty-four patients with proven squamous cell carcinomas of the larynx (T1-T4) were studied using dynamic TYR PET. The PSRs of tumor and nontumor (background) regions were determined. Four different methods were used to calculate the SUV: uncorrected SUV (SUV(BW)); and SUVs corrected for body surface area (SUV(BSA)), for lean body mass (SUV(LBM)), and for the Quetelet index (SUV(QI)). Correlations between PSR values and SUVs were calculated. RESULTS: The PSR of all tumors was significantly higher (P < 0.001) than the PSR of nontumor tissue. The correlations of SUV(BW), SUV(BSA), SUV(LBM), and SUV(QI) with the quantitative values of the PSR were high (r = 0.84-0.90). The best correlation was observed with the SUV based on the LBM (SUV(LBM)). CONCLUSION: High correlation between the quantitative values (PSR) and the SUVs offers the possibility to use noninvasive TYR PET for detection and reliable quantification of primary head and neck tumors.

Carbon-11 tyrosine PET for visualization and protein synthesis rate assessment of laryngeal and hypopharyngeal carcinomas.

Accurate assessment of tumour extent and lymph node involvement in squamous cell carcinomas of the head and neck region is essential for therapy planning. Unfortunately, conventional diagnostic examination and imaging techniques, which monitor tumours on the basis of anatomical parameters, have drawbacks in clinical practice. The aim of this study was to investigate the feasibility of L-[1-(11)C]-tyrosine (TYR) positron emission tomography (PET) for visualisation of squamous cell carcinoma of the larynx and hypopharynx and quantification of tumour activity by assessment of protein synthesis rate (PSR). Dynamic TYR PET was performed on 31 patients with T1-T4 laryngeal or hypopharyngeal carcinoma before therapy. Plasma activity of TYR, (11)CO(2) and (11)C-protein levels were measured, and PSRs were calculated for primary malignancies. All 31 laryngeal and hypopharyngeal tumours were visualised as a hotspot (sensitivity 100%). The median PSR of the tumours (2.06 nmol ml(-1) min(-1); range 0.72-6.96) was significantly higher ( P<0.001) than that of non-tumour (background) tissue (0.51 nmol ml(-1) min(-1); range 0.22-0.89). L-[1-(11)C]-Tyrosine PET appears to be a potential method for visualisation of primary laryngeal and hypopharyngeal tumours. In vivo quantification of tumour activity by assessment of PSR is possible and may have a future role in the therapy planning and therapy evaluation of laryngeal and hypopharyngeal tumours.

Positron emission tomography: the conceptual idea using a multidisciplinary approach.

Positron emission tomography (PET) is a method for quantitatively measuring biochemical and physiological processes in vivo by using radiopharmaceuticals labeled with positron-emitting radionuclides such as 11C, 13N, 15O, and 18F and by measuring the annihilation radiation using a coincidence technique. This technique is also used for measurement of the pharmacokinetics of labeled drugs and measurement of the effects of drugs on metabolism. Deviations from normal metabolism can be measured and insight into biological processes responsible for diseases can be obtained.

Comparison of (11)C-choline and (18)F-FDG PET in primary diagnosis and staging of patients with thoracic cancer.

UNLABELLED: PET with (18)F-FDG is used for detection and staging of thoracic cancer; however, more specific PET radiopharmaceuticals would be welcome. (11)C-labeled choline (CHOL) is a new radiopharmaceutical potentially useful for tumor imaging, since it is incorporated into cell membranes as phosphatidylcholine. The aim of this study was to investigate whether (11)C-CHOL PET has advantages over (18)F-FDG PET in patients with thoracic cancer. METHODS: We evaluated 17 patients with thoracic cancer both with (11)C-CHOL PET and (18)F-FDG PET. After transmission scanning, (11)C-CHOL was injected intravenously, and whole-body scanning was started after 5 min. Immediately thereafter, (18)F-FDG was injected intravenously, followed after 90 min by interleaved attenuation-corrected whole-body scanning. Scans were performed from crown to femur. Visual and quantitative (standardized uptake value) analyses of (11)C-CHOL PET and (18)F-FDG PET were performed and compared with results of traditional staging and follow-up. RESULTS: The most prominent features of normal (11)C-CHOL distribution were high uptake in liver, renal cortex, and salivary glands. Except for some uptake in choroid plexus and pituitary gland, brain uptake was negligible. All primary thoracic tumors were detected with (11)C-CHOL PET and (18)F-FDG PET. Both (11)C-CHOL PET and (18)F-FDG PET correctly identified all 16 patients with lymph node involvement. However, in a lesion-to-lesion analysis, (11)C-CHOL PET detected only 29 of 43 metastatic lymph nodes, whereas (18)F-FDG PET detected 41 of 43. (11)C-CHOL PET detected fewer intrapulmonary and pleural metastases than (18)F-FDG PET (27/47 vs. 46/47). More brain metastases were detected with (11)C-CHOL PET (23/23) than with (18)F-FDG PET (3/23). For primary tumors, the median (range) standard uptake values of (11)C-CHOL and (18)F-FDG were 1.68 (0.98-3.22) and 4.22 (1.40-8.26), respectively (P = 0.001). CONCLUSION: (11)C-CHOL PET can be used to visualize thoracic cancers. Although detection of lymph node metastases with (11)C-CHOL PET was inferior compared with (18)F-FDG PET, the detection of brain metastases was superior.