18f-faza and Neoplasms

18F-FDG is a most popular radiopharmaceutical for tumor diagnosis in the world. In addition, 11C-methionine, 18F-FLT and 11C-choline have been used to compensate for drawbacks of 18F-FDG. Now, novel radiopharmaceuticals are required to estimate or predict therapeutic efficacy because we have many strategies to treat tumors. Radiotherapy which damage DNA by producing free radicals is commonly used to treat various types of tumors. Hypoxia is closely associated with resistance to chemo- and/or radiotherapy and is a common feature of solid tumors. Recently, understanding of tumor hypoxia in oncology has led to development of radiopharmaceuticals for hypoxia imaging. This review provides an overview of PET radiopharmaceuticals for hypoxia imaging and 18F-FBPA which is used for boron neutron capture therapy.

Topics: Animals; Boron Compounds; Boron Neutron Capture Therapy; Coordination Complexes; Fluorine Radioisotopes; Humans; Hypoxia; Misonidazole; Neoplasms; Nitroimidazoles; Organometallic Compounds; Phenylalanine; Positron-Emission Tomography; Radiopharmaceuticals; Thiosemicarbazones

A wide variety of imaging approaches have been developed in the past few decades for monitoring tumor oxygenation and hypoxia in vivo. In particular, nuclear medicine has seen the development of several radiolabeled hypoxia markers and is the preferred method for imaging of tumor hypoxia. Hypoxia imaging is increasingly being used in the clinical setting and is progressing from a mere detection method to application in individualization of chemoradiotherapy.

Topics: Humans; Hypoxia; Misonidazole; Neoplasms; Neovascularization, Pathologic; Nitroimidazoles; Positron-Emission Tomography; Radiography; Radiopharmaceuticals

Tumour hypoxia is thought to play a significant role in the outcome of solid tumour therapy. Positron emission tomography (PET) is the best-validated noninvasive technique able to demonstrate the presence of hypoxia in vivo. The locally developed PET tracer for imaging hypoxia, 1-alpha-D: -(5-deoxy-5-[(18)F]-fluoroarabinofuranosyl)-2-nitroimidazole ((18)F-FAZA), has been shown to accumulate in experimental models of tumour hypoxia and to clear rapidly from the circulation and nonhypoxic tissues. The safety and general biodistribution patterns of this radiopharmaceutical in patients with squamous cell carcinoma of the head and neck (HNSCC), small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC), malignant lymphoma, and high-grade gliomas, were demonstrated in this study.. Patients with known primary or suspected metastatic HNSCC, SCLC or NSCLC, malignant lymphoma or high-grade gliomas were dosed with 5.2 MBq/kg of (18)F-FAZA, then scanned 2-3 h after injection using a PET or PET/CT scanner. Images were interpreted by three experienced nuclear medicine physicians. The location and relative uptake scores (graded 0 to 4) of normal and abnormal (18)F-FAZA biodistribution patterns, the calculated tumour-to-background (T/B) ratio, and the maximum standardized uptake value were recorded.. Included in the study were 50 patients (32 men, 18 women). All seven patients with high-grade gliomas showed very high uptake of (18)F-FAZA in the primary tumour. In six out of nine patients with HNSCC, clear uptake of (18)F-FAZA was observed in the primary tumour and/or the lymph nodes in the neck. Of the 21 lymphoma patients (15 with non-Hodgkin's lymphoma and 6 with Hodgkin's disease), 3 demonstrated moderate lymphoma-related uptake. Of the 13 lung cancer patients (12 NSCLC, 1 SCLC), 7 had increased (18)F-FAZA uptake in the primary lung tumour. No side effects of the administration of (18)F-FAZA were observed.. This study suggests that (18)F-FAZA may be a very useful radiopharmaceutical to image hypoxia in the tumour types selected. Especially the high uptake by gliomas was encouraging. Given the good imaging properties, including acceptable T/B ratios in the tumour categories studied, (18)F-FAZA could be considered as a very promising agent for assessing the hypoxic fraction of these tumour types.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Fluorine Radioisotopes; Glioma; Head and Neck Neoplasms; Humans; Hypoxia; Lung Neoplasms; Lymphoma; Male; Middle Aged; Neoplasms; Nitroimidazoles; Positron-Emission Tomography; Radiopharmaceuticals; Young Adult

1-α-D-(5-Deoxy-5-[18F]fluoroarabinofuranosyl)-2-nitroimidazole([18F] FAZA) is a PET radiotracer that demonstrates excellent potential in imaging regional hypoxia, and is clinically used in diagnosing a wide range of solid tumors in cancer patients. [18F]FAZA, however, is radiofluorinated in only moderate recovered radiochemical yield (rRCY, ~12%). It is postulated that the relative stability of the C1' β-anomeric bond at C5' will make 1-β-D-(5-fluoro-5-deoxyarabinofuranosyl)-2-nitroimidazole (β-FAZA), the β-conformer of FAZA, an attractive candidate for clinical hypoxia imaging.. The principle goals were to synthesize β-FAZA and β-Ac2TsAZA, the radiofluorination precursor, to establish the radiofluorination chemistry leading to β-[18F]FAZA, and to investigate the biodistribution of β-[18F]FAZA in an animal tumor-bearing model using PET imaging.. The appropriately-protected furanose sugar was coupled with 2-nitroimidazole to afford 1-β-D-(2,3-di-O-acetylarabinofuranosyl)-2-nitroimidazole (β-Ac2AZA). Fluorination of β-Ac2AZA with DAST, followed by alkaline hydrolysis, afforded β-FAZA (21%). The radiolabeling synthon, 1-β-D-(5-O-toluenesulfonyl-2,3-di-O-acetylarabinofuranosyl)-2-nitroimidazole (β-Ac2TsAZA), on radiofluorination using the 18F/K222 complex under various reaction conditions, followed by base-catalyzed deacetylation, afforded β-[18F]FAZA. β-[18F]FAZA was radiochemically stable for at least 8 h when stored in aqueous ethanol (8%) at 22 °C. A preliminary PET imaging-based biodistribution study of β-[18F]FAZA was performed in A431 tumor-bearing nude mice.. β-FAZA and β-Ac2TsAZA were synthesized in satisfactory yield. Radiochemistry of [18F]FAZA was established. PET images showed strong uptake in hypoxic regions of the tumor.. The synthesis of β-FAZA and β-[18F]FAZA are reported. Radiofluorination of β-Ac2TsAZA and the deprotection of β-Ac2[18F]FAZA were facile, but led to a more complex mixture of radiofluorinated by-products than observed with the corresponding precursor of α-[18F]FAZA. PET images were indicative of hypoxia-selective accumulation of β-[18F]FAZA in tumor.

Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Fluorine Radioisotopes; Male; Mice; Mice, Nude; Neoplasms; Nitroimidazoles; Positron-Emission Tomography; Radiochemistry; Radiopharmaceuticals; Tissue Distribution; Tumor Hypoxia

(18)F-fluoroazomycin arabinoside ((18)F-FAZA) is a PET tracer of tumor hypoxia. However, as hypoxia often is associated with decreased perfusion, the delivery of (18)F-FAZA may be compromised, potentially disturbing the association between tissue hypoxia and (18)F-FAZA uptake. The aim of this study was to gain insight into the relationship between tumor perfusion and (18)F-FAZA uptake.. Ten patients diagnosed with advanced non-small cell lung cancer underwent subsequent dynamic (15)O-H2O and (18)F-FAZA PET scans with arterial sampling. Parametric images of both (15)O-H2O-derived perfusion (tumor blood flow [TBF]) and volume of distribution (V(T)) of (18)F-FAZA were generated. Next, multiparametric classification was performed using lesional and global thresholds. Voxels were classified as low or high TBF and (18)F-FAZA V(T), respectively. Finally, by combining these initial classifications, voxels were allocated to 4 categories: lowTBF-lowV(T), lowTBF-highV(T), highTBF-lowV(T), and highTBF-highV(T).. A total of 13 malignant lesions were identified in the 10 patients. The TBF and (18)F-FAZA V(T) values (average ± SD) across all lesions were 0.45 ± 0.20 mL·cm(-3)·min(-1) and 0.94 ± 0.31 mL·cm(-3), respectively. The averages of all lesional median values for TBF and (18)F-FAZA V(T) were 0.37 ± 0.15 mL·cm(-3)·min(-1) and 0.85 ± 0.18 mL·cm(-3), respectively. Multiparametric analysis showed that classified voxels were clustered rather than randomly distributed. Several intralesion areas were identified where (18)F-FAZA V(T) was inversely related to TBF. On the other hand, there were also distinct areas where TBF as well as (18)F-FAZA V(T) were decreased or increased.. The present data indicate that spatial variation of (18)F-FAZA uptake is not necessarily inversely related to TBF. This suggests that decreased TBF may result in flow-limited delivery of (18)F-FAZA. Areas with both high (18)F-FAZA uptake and high TBF values suggest that high (18)F-FAZA uptake, possibly suggesting hypoxia, may occur despite high TBF values. In conclusion, multiparametric evaluation of the spatial distributions of both TBF and (18)F-FAZA uptake may be helpful for understanding the (18)F-FAZA signal.

Topics: Aged; Carcinoma, Non-Small-Cell Lung; Cluster Analysis; Female; Humans; Hypoxia; Lung Neoplasms; Male; Middle Aged; Neoplasms; Nitroimidazoles; Oxygen Radioisotopes; Positron-Emission Tomography; Radiopharmaceuticals; Regional Blood Flow; Water

CT26 colon carcinoma-bearing mice were anesthetized with isoflurane (IF) or ketamine/xylazine (KX) while breathing air or oxygen (O2). We performed 10 min static PET scans 1 h, 2 h and 3 h after [18F]FAZA injection and calculated the [18F]FAZA-uptake and tumor-to-muscle ratios (T/M). In another experimental group, we placed a pO2 probe in the tumor as well as in the gastrocnemius muscle to measure the pO2 and perfusion.. Ketamine/xylazine-anesthetized mice yielded up to 3.5-fold higher T/M-ratios compared to their isoflurane-anesthetized littermates 1 h, 2 h and 3 h after [18F]FAZA injection regardless of whether the mice breathed air or oxygen (3 h, KX-air: 7.1 vs. IF-air: 1.8, p = 0.0001, KX-O2: 4.4 vs. IF-O2: 1.4, p < 0.0001). The enhanced T/M-ratios in ketamine/xylazine-anesthetized mice were mainly caused by an increased [18F]FAZA uptake in the carcinomas. Invasive pO2 probe measurements yielded enhanced intra-tumoral pO2 values in air- and oxygen-breathing ketamine/xylazine-anesthetized mice compared to isoflurane-anesthetized mice (KX-air: 1.01 mmHg, IF-air: 0.45 mmHg; KX-O2 9.73 mmHg, IF-O2: 6.25 mmHg). Muscle oxygenation was significantly higher in air-breathing isoflurane-anesthetized (56.9 mmHg) than in ketamine/xylazine-anesthetized mice (33.8 mmHg, p = 0.0003).. [18F]FAZA tumor uptake was highest in ketamine/xylazine-anesthetized mice regardless of whether the mice breathed air or oxygen. The generally lower [18F]FAZA whole-body uptake in isoflurane-anesthetized mice could be due to the higher muscle pO2-values in these mice compared to ketamine/xylazine-anesthetized mice. When performing preclinical in vivo hypoxia PET studies, oxygen should be avoided, and ketamine/xylazine-anesthesia might alleviate the identification of tumor hypoxia areals.

Topics: Anesthesia; Animals; Blood Pressure; Cell Line, Tumor; Female; Isoflurane; Ketamine; Mice, Inbred BALB C; Molecular Probes; Muscles; Neoplasms; Nitroimidazoles; Oxygen; Partial Pressure; Perfusion; Positron-Emission Tomography; Respiration; Systole; Xylazine

Several 2-nitroimidazole-based molecules (NIs) are used as clinical hypoxic tumor radiodiagnostics, but they are not effective as radiosensitizers/radiochemotherapeutics. These NIs permeate tumor cells nonselectively via diffusion, and in therapy, where high doses are required, their dose limiting toxicities preclude success. The synthesis and preliminary in vitro evaluations of three glucoazomycins, members of a novel class of C6-O-glucose-linked-azomycin conjugates that are putative substrates of glucose transport proteins (GLUTs) and possess hypoxia-selective radiosensitization features, are now reported. The hypoxia-dependent upregulation of several GLUTs provides a rational basis to develop these glucoazomycins because more selective uptake in hypoxic cells would decrease systemic toxicities at effective doses. Calculated partition coefficients (ClogP, -1.70 to -2.99) predict rapid in vivo clearance for low systemic toxicity. In vitro experimental data show that glucoazomycins are radiosensitizers and that they competitively inhibit glucose uptake.

Topics: Cell Hypoxia; Cell Line, Tumor; Drug Design; Glucose Transport Proteins, Facilitative; Glucosides; Glycosides; Humans; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Misonidazole; Neoplasms; Nitroimidazoles; Radiation-Sensitizing Agents; Radionuclide Imaging; Radiopharmaceuticals; Transcriptional Activation

Microfluidic technology allows fast reactions in a simple experimental setup, while using very low volumes and amounts of starting material. Consequently, microfluidic technology is an ideal tool for radiolabeling reactions involving short-lived positron emitters. Optimization of the complex array of different reaction conditions requires knowledge of the different reaction parameters linked to the microfluidic system as well as their influence on the radiochemical yields. 1-(5-Deoxy-5-fluoro-α-d-arabinofuranosyl)-2-nitroimidazole ([(18)F]FAZA) is a frequently used radiotracer for PET imaging of tumor hypoxia. The present study describes the radiosynthesis of [(18)F]FAZA by means of microfluidic technology and subsequent small animal PET imaging in EMT-6 tumor-bearing mice.. Radiosyntheses were performed using the NanoTek Microfluidic Synthesis System (Advion BioSciences, Inc.). Optimal reaction conditions were studied through screening different reaction parameters like temperature, flow rate, residency time, concentration of the labeling precursor (1-(2,3-di-O-acetyl-5-O-tosyl-α-d-arabinofuranosyl)-2-nitroimidazole) and the applied volume ratio between the labeling precursor and [(18)F]fluoride.. Optimized reaction conditions at low radioactivity levels (1 to 50 MBq) afforded 63% (decay-corrected) of HPLC-purified [(18)F]FAZA within 25 min. Higher radioactivity levels (0.4 to 2.1 GBq) gave HPLC-purified [(18)F]FAZA in radiochemical yields of 40% (decay-corrected) within 60 min at a specific activity in the range of 70 to 150 GBq/μmol. Small animal PET studies in EMT-6 tumor-bearing mice showed radioactivity accumulation in the tumor (SUV(20min) 0.74 ± 0.08) resulting in an increasing tumor-to-muscle ratio over time.. Microfluidic technology is an ideal method for the rapid and efficient radiosynthesis of [(18)F]FAZA for preclinical radiopharmacological studies. Careful analysis of various reaction parameters is an important requirement for the understanding of the influence of different reaction parameters on the radiochemical yield using microfluidic technology. Exploration of microfluidic technology for the radiosynthesis of other PET radiotracers in clinically relevant radioactivity levels is currently in progress.

Topics: Animals; Cell Hypoxia; Cell Line, Tumor; Female; Mice; Mice, Inbred BALB C; Microfluidic Analytical Techniques; Neoplasms; Nitroimidazoles; Positron-Emission Tomography; Radiochemistry; Ribose

The aim of this study was to develop an efficient fully automated synthesis method to achieve a high radiochemical yield of [(18)F]FAZA with a small amount of precursor. A small cartridge containing 25mg of the QMA resin was prepared and evaluated to obtain [(18)F]F(-) in a small quantity of base (K(2)CO(3)), which might allow the use of a small amount of precursor. The labeling and hydrolyzing conditions for [(18)F]FAZA synthesis were also investigated manually. No-carrier-added [(18)F]F(-) was trapped on the small QMA cartridge and eluted with a mixture of Krytofix 222 (2.26 mg, 6.0 μmol) and K(2)CO(3) (0.69 mg, 5.0 μmol) in 70% MeCN (0.4 mL). The automated synthesis of [(18)F]FAZA was optimally performed with a modified NIRS original synthesis system for clinical use, by labeling 2.5mg (5.2 μmol) of the precursor in DMSO (0.4 mL) at 120°C for 10 min, and then by hydrolyzing the (18)F-labeled intermediate with 0.1M NaOH (0.5 mL) at room temperature for 3 min. Using the above condition, the [(18)F]FAZA injection was obtained with a high radiochemical yield of 52.4±5.3% (decay-corrected, n=8) within 50.5±1.5 min.

Topics: Automation; Cell Hypoxia; Fluorine Radioisotopes; Humans; Neoplasms; Nitroimidazoles

Positron emission tomography (PET) allows non-invasive detection and mapping of tumor hypoxia. However, slow tracer kinetics and low resolution, results in limited tumor-to-normal tissue contrast and the risk of missing areas where hypoxic cells are intermixed with necrosis. The shape of tumor time activity curves (TACs), as deduced from dynamic scans, may allow further separation of tumors/tumor sub-volumes that are inseparable based on static scans. This study was designed to define the added value of dynamic scans.. Three squamous cell carcinoma tumor models were grown in mice. Mice were injected with the (18)F-labeled PET hypoxia-tracer fluoroazomycin arabinoside (FAZA) and the immunologically-detectable hypoxia-marker pimonidazole, and PET scanned dynamically for three to six hours. Subsequently, microregional tracer retention (autoradiography) and the distribution of pimonidazole-retaining cells (immunohistology) and necrosis were analyzed in tumor tissue sections. Dynamic PET data were analysed based on a two-compartment model with irreversible tracer binding generating estimates of the putative hypoxia surrogate markers k(3) (tracer trapping rate constant) and K(i) (influx rate constant from plasma into irreversible bound tracer).. High tumor-to-reference tissue ratios and a strong linear correlation (R∼0.7 to 0.95) between density of hypoxic cells and FAZA concentration was observed three hours after tracer administration, suggesting that late time PET images provides an accurate measure of hypoxia against which kinetic model estimates can be validated. Tumor TACs varied widely (ranging from distinctly wash-out to accumulative type) among tumor types although pimonidazole-stainings revealed extensive hypoxia in all models. Kinetic analysis of tumor sub-volumes showed that k(3) correlated poorly with late time FAZA retention regionally in two of the three tumor models. The influx rate constant K(i) displayed far less variability and correlated strongly with late time FAZA retention (hypoxia) in two of three tumor models, whereas a non-consistent relationship was observed in the last tumor model. Our study demonstrates the potential usefulness of dynamic PET, but also that a simple two-compartment model may be inappropriate in some tumor models.

Topics: Animals; Carcinoma, Squamous Cell; Female; Gingival Neoplasms; Humans; Hypoxia; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Neoplasms; Nitroimidazoles; Positron-Emission Tomography; Transplantation, Heterologous; Tumor Cells, Cultured; Uterine Cervical Neoplasms

Solid tumors contain microenvironmental regions of hypoxia that present a barrier to traditional radiotherapy and chemotherapy, and this work describes a novel approach to circumvent hypoxia. We propose to overcome hypoxia by augmenting the effectiveness of drugs that are designed to specifically kill hypoxic tumor cells.. We have constructed RKO colorectal tumor cells that express a small RNA hairpin that specifically knocks down the hypoxia-inducible factor 1a (HIF1a) transcription factor. We have used these cells in vitro to determine the effect of HIF1 on cellular sensitivity to the hypoxic cytotoxin PR-104, and its role in cellular oxygen consumption in response to the pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA). We have further used these cells in vivo in xenografted tumors to determine the role of HIF1 in regulating tumor hypoxia in response to DCA using (18)F-fluoroazomycin arabinoside positron emission tomography, and its role in regulating tumor sensitivity to the combination of DCA and PR-104.. HIF1 does not affect cellular sensitivity to PR-104 in vitro. DCA transiently increases cellular oxygen consumption in vitro and increases the extent of tumor hypoxia in vivo as measured with (18)F-fluoroazomycin arabinoside positron emission tomography. Furthermore, we show that DCA-dependent alterations in hypoxia increase the antitumor activity of the next-generation hypoxic cytotoxin PR-104.. DCA interferes with the HIF-dependent "adaptive response," which limits mitochondrial oxygen consumption. This approach transiently increases tumor hypoxia and represents an important method to improve antitumor efficacy of hypoxia-targeted agents, without increasing toxicity to oxygenated normal tissue.

Topics: Animals; Cell Hypoxia; Cell Line, Tumor; Dose-Response Relationship, Drug; Fluorine Radioisotopes; Humans; Mice; Mice, Nude; Mitochondria; Neoplasm Transplantation; Neoplasms; Nitrogen Mustard Compounds; Nitroimidazoles; Oxygen Consumption; Positron-Emission Tomography; Radiopharmaceuticals

Tumour hypoxia and elevated glycolysis (Warburg effect) predict poor prognosis. Each parameter is assessable separately with positron emission tomography, but they are linked through anaerobic glycolysis (Pasteur effect). Here, we compare the oxygenation-dependent retention of fluoroazomycin arabinoside ([(18)F]FAZA), a promising but not well-characterised hypoxia-specific tracer, and fluorodeoxyglucose ([(18)F]FDG) in four carcinoma cell lines.. Cells seeded on coverslips were positioned in modified Petri dishes that allow physically separated cells to share the same tracer-containing medium pool. Following oxic, hypoxic or anoxic tracer incubation, coverslips were analysed for radioactivity ([(18)F]FDG + [(18)F]FAZA) or re-incubated in tracer-free oxygenated medium and then measured ([(18)F]FAZA). Next, we tested the reliability of [(18)F]FDG as a relative measure of glucose metabolic rate. Finally, from two cell lines, xenografts were established in mice, and the tracer distribution between hypoxic and well-oxygenated areas were deduced from tissue sections.. Three hours of anoxia strongly stimulated [(18)F]FAZA retention with anoxic-to-oxic uptake ratios typically above 30. Three out of four cell lines displayed similar selectivity of [(18)F]FDG versus glucose, but oxic uptake and anoxic-to-oxic uptake ratio of [(18)F]FDG varied considerably. Although less pronounced, [(18)F]FAZA also showed superior in vivo hypoxia specificity compared with [(18)F]FDG.. [(18)F]FAZA displays excellent in vitro characteristics for hypoxia imaging including modest cell-to-cell line variability and no binding in oxic cells. In contrast, the usability of [(18)F]FDG as a surrogate marker for hypoxia is questionable due to large variations in baseline (oxic) glucose metabolism and magnitudes of the Pasteur effects.

Topics: Animals; Binding, Competitive; Biological Transport; Cell Count; Cell Line, Tumor; Female; Fluorodeoxyglucose F18; Glucose; Humans; Hypoxia; Mice; Neoplasms; Nitroimidazoles; Oxygen; Positron-Emission Tomography; Time Factors

Topics: Autoradiography; Cell Hypoxia; Glucosides; Humans; Neoplasms; Neovascularization, Pathologic; Nitroimidazoles; Oligopeptides; Positron-Emission Tomography

The study was performed to compare the (18)F-labeled nitroimidazole compound fluoroazomycin arabinoside ((18)F-FAZA) with the standard hypoxia tracer fluoromisonidazole ((18)F-FMISO) in detection of tumor tissue hypoxia and to verify the oxygenation dependency of (18)F-FAZA uptake.. Biodistribution of (18)F-FAZA was studied at various time points in EMT6 tumor-bearing BALB/c mice and in AR42J and A431 tumor-bearing nude mice and compared with that of (18)F-FMISO. The presence of tumor tissue hypoxia was verified in 5 EMT6 and 5 AR42J tumors using an oxygen-sensing needle electrode system. To evaluate the oxygenation dependency of (18)F-FAZA uptake, using the Munich prototype animal PET scanner, 2 serial PET scans were performed in 13 A431 tumor-bearing nude mice breathing pure oxygen or room air on 1 d and then selecting the other oxygen breathing condition on the following day. In addition, digital autoradiography was performed with EMT6 tumor-bearing (18)F-FAZA-dosed, nude mice breathing either room air (n = 8) or carbogen (n = 9).. Tissue partial pressure of oxygen (Po(2)) electrode measurements revealed that tumor hypoxia was present under room air breathing in EMT6 (tissue Po(2) = 2.9 +/- 2.6) and AR42J tumors (tissue Po(2) = 0.4 +/- 0.2), which was significantly lower compared with that of reference tissue (tissue Po(2) = 25.8 +/- 6.7 and tissue Po(2) = 29.0 +/- 3.0 [mean +/- SD], respectively; P < 0.01). In all tumor models, (18)F-FAZA displayed significantly higher tumor-to-muscle and tumor-to-blood ratios compared with (18)F-FMISO, indicating a faster clearance of (18)F-FAZA from normal tissues. In AR42J tumors, (18)F-FAZA tumor-to-normal ratios were found to increase over time. Serial animal (18)F-FAZA PET studies showed that the tumor-to-background ratio was significantly higher in animals breathing room air compared with that of animals breathing pure oxygen (7.3 +/- 2.3 vs. 4.2 +/- 1.2, respectively; P < 0.001). Similarly, autoradiography showed significantly higher tumor-to-muscle ratios in mice breathing room air compared with those of animals breathing carbogen (5.3 +/- 0.8 vs. 2.2 +/- 0.8; respectively; P < 0.02).. (18)F-FAZA shows superior biokinetics and is, thus, a promising PET tracer for the visualization of tumor hypoxia. This study also verified a hypoxia-specific uptake mechanism for (18)F-FAZA in murine tumor models.

Topics: Animals; Cell Hypoxia; Disease Models, Animal; Female; Metabolic Clearance Rate; Mice; Mice, Inbred BALB C; Mice, Nude; Misonidazole; Neoplasms; Nitroimidazoles; Organ Specificity; Oxidation-Reduction; Oxygen; Radionuclide Imaging; Radiopharmaceuticals; Tissue Distribution