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Positron emission tomography imaging of constitutive peripheral…
98 Molecular Imaging and Biology, Volume 6, Number 2
with three different coupling conditions along the length of the common interface. The fabrication required considerable effort to apply the different optical coupling schemes. Also, the use of multi-anode PMTs resulted in a relatively high cost per channel for the decoding electronics. Our current efforts are focused at developing a more cost effective fabrication technique along with the use of smaller cross section crystals (1x1x20 mm). The fabrication is based on the use of the 3M polymer used in the MiCE2 module design but laser cut into patterns to control the amount of light shared between adjacent crystals as a function of the long axis length. The crystals and polymer film are then glued together (laminated) to form the final detector module. Thus far, we have reproduced the original 4x4x30 mm crystal data with our new fabrication technique. Experiments with the smaller crystal cross sections are now underway. If we can successfully use this approach with smaller cross section crystals and 6+6 position sensitive photomultiplier tubes, then we will be able to provide a cost effective detector module design for a high resolution, high sensitivity small animal positron emission tomography (PET) scanner. No. 110 LOW DENSITY LIPOPROTEIN TARGETED PHOTODYNAMIC THERAPY H. Li1, Z. Zhang2, M. Zhang3, D. Blessington1, T. M. Busch1, B. Chance1, J. D. Glickson1, G. Zheng1 1University of Pennsylvania, Philadelphia, PA, 2Huazhong University of Science and Technology, Wu Han, CHINA, 3Shang Hai University, Shang Hai, CHINA. Targeted photodynamic therapy (PDT) is a promising new modality for cancer treatment. Many tumors overexpress low-density lipoprotein LDL receptors (LDLrs) due to increased requirement of cholesterol for membrane synthesis, therefore LDL can be used as an anticancer agents carrier. Neutral chlorophyll dye attached to cholesterol fatty acid esters was synthesized and reconstituted into the lipid core of LDL (Pyro-CE-LDL). 3nmol/g of Pyro-CE-LDL was intravenously injected into HepG2 tumorbearing mouse, which was known to overexpress LDLrs. PDT was carried out using a KTP YAG pumped dye module tuned to produce 670nm light. The light was delivered at a fluorescence rate 150mw/cm2 to a total dose of 300J/cm2. Tumor tissue was scanned by 3-D surface fluorometric scanner for oxidized (Fp), reduced (PN) flavoprotein signals and for Pyro-CE fluorescence. We observed increased Fp signal and decreased PN signal in the PDT treated sample, which resulted in the significantly increased redox ratio. The ratio of Fp/(Fp+PN) represents the redox state of the mitochondrial NAD/NADH redox couple, therefore, can be used to evaluate the PDT damage to the tumor mitochondria. Pyro-CE signal matched very well with the increased redox ratio spot. For the light control sample, no Pyro-CE signal could be detected, and no effect on the Fp and PN signals, which clearly indicated that the PDT response was due to Pyro-CE-LDL photosensitization. In conclusion, with 720nm emission, Pyro-CE-LDL can be used as a tumor selective near infrared fluorescence imaging probe and as a specific PDT agent for the LDLrs overexpressed tumor model. No. 111 DIFFERENTIAL 3’-[18F]FLUORO-3’-DEOXYTHYMIDINE AND 2-DEOXY-2-[18F]FLUORO-D-GLUCOSE UPTAKE IN MURINE MODELS OF HUMAN SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK B. J. Lopresti1, S. M. Thomas2, C. A. Mathis1, N. S. Mason1, J. A. Ruszkiewicz1, J. R. Grandis2 1University of Pittsburgh Dept. of Radiology, Pittsburgh, PA, 2University of Pittsburgh Dept. of Otolaryngology, Pittsburgh, PA. Introduction: Imaging squamous cell carcinoma of the head and neck (SCCHN) in animal models with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and 3’-[18F]fluoro-3’-deoxythymidine (FLT) microPET may represent a
valuable investigational tool for evaluating antitumor response to novel therapeutics in terms of tumor metabolism and cell proliferation rates. Methods: SCCHN cell lines 1483 (n = 3) and 22b (n = 4) were injected subcutaneously in athymic nude mice. MicroPET using a Concorde P4 system was performed when tumors grew to be 4-5 mm in diameter. Animals were anesthetized (isoflurane) and injected with 150-200 µCi of either FLT or FDG. Emission data were collected for 90 minutes and standardized uptake value (SUV) in tumors determined. Each animal was scanned twice, once with each radiotracer, on subsequent days. Results: Uptake of FDG was greatest in heart and brain and elevated in other peripheral tissues. No increase in FDG uptake was observed in 22b (SUV = 1.04 ± 0.11) or 1483 (SUV = 0.97 ± 0.08) tumors. No significant increase in FLT uptake in 22b tumors was observed (SUV = 1.09± 0.16), while 1483 cell tumors showed substantially elevated uptake of FLT (SUV = 2.08 ± 0.39; range: 1.8 - 2.8). Time-activity curves following FLT injection show constant accumulation in tumor, negligible uptake in brain, and an otherwise uniform distribution. Conclusion: FDG uptake in 22b and 1483 tumors was relatively low. Uptake of FLT was elevated in 1483 tumors, but not 22b’s. A similar characterization of other xenografted SCCHN cell lines is ongoing. No. 112 POSITRON EMISSION TOMOGRAPHY IMAGING OF CONSTITUTIVE PERIPHERAL BENZODIAZEPINE RECEPTOR EXPRESSION IN RAT BRAIN USING [C-11]DAA1106 : COMPARISON WITH [C-11]PK-11195 B. J. Lopresti1, N. S. Mason1, S. Kendro1, C. A. Mathis1, T. Suhara2, J. Maeda2, S. Venneti3, C. A. Wiley3 1University of Pittsburgh Dept. of Radiology, Pittsburgh, PA, 2National Institute of Radiological Sciences, Chiba, JAPAN, 3University of Pittsburgh Dept. of Pathology, Pittsburgh, PA. Introduction: Neuroinflammatory responses to central nervous system (CNS) insults may trigger significant upregulation of peripheral benzodiazepine receptor (PBDR) expression on intrinsic activated microglia and infiltrated macrophages. in vivo positron emission tomography (PET) investigations using [C-11]1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinoline carboxamide ([C-11]PK-11195) have demonstrated increased binding in several neurodegenerative and autoimmune diseases. However, low brain uptake and high non-displaceable binding have complicated quantitative analyses. DAA1106 (N-(2,5-dimethoxybenzyl)-N-(5fluoro-2-phenoxyphenyl)acetamide) is a potent (KD = 0.12 nM) and selective PBDR agonist which, labeled with carbon-11, is a promising PET PBDR radioligand with many superior imaging properties. The purpose of this study was to demonstrate specific and reversible binding of [C11]DAA1106 to constitutive levels of PBDR sites in rat brain. Methods: Rats (n=3) were anesthetized (isoflurane) and positioned in a microPET P4 scanner to simultaneously image brain and lungs. The lungs contain a high density of PBDR sites and primarily reflect the kinetic behavior of specific binding. Rats were injected with either [C-11]DAA1106 or [C-11]PK11195 (750 -1500 µCi) and emission data collected for 60 minutes. At 15 minutes post-injection, a displacing dose of unlabeled DAA1106 (1.0 mg/kg) was administered for 60 seconds. Results: [C-11]DAA1106 radioactivity was rapidly and effectively displaced for 10 minutes by unlabeled DAA1106 in both lungs (-92%) and brain (- 75%). [C-11]PK-11195 radioactivity was displaced by unlabeled DAA1106 in lung (- 55%), but not brain (+ 24%). Conclusion: [C-11]DAA1106 kinetics in normal rat brain are analogous to those in lung and are dominated by specific binding while [C-11]PK11195 normal brain kinetics are not.
with three different coupling conditions along the length of the common interface. The fabrication required considerable effort to apply the different optical coupling schemes. Also, the use of multi-anode PMTs resulted in a relatively high cost per channel for the decoding electronics. Our current efforts are focused at developing a more cost effective fabrication technique along with the use of smaller cross section crystals (1x1x20 mm). The fabrication is based on the use of the 3M polymer used in the MiCE2 module design but laser cut into patterns to control the amount of light shared between adjacent crystals as a function of the long axis length. The crystals and polymer film are then glued together (laminated) to form the final detector module. Thus far, we have reproduced the original 4x4x30 mm crystal data with our new fabrication technique. Experiments with the smaller crystal cross sections are now underway. If we can successfully use this approach with smaller cross section crystals and 6+6 position sensitive photomultiplier tubes, then we will be able to provide a cost effective detector module design for a high resolution, high sensitivity small animal positron emission tomography (PET) scanner. No. 110 LOW DENSITY LIPOPROTEIN TARGETED PHOTODYNAMIC THERAPY H. Li1, Z. Zhang2, M. Zhang3, D. Blessington1, T. M. Busch1, B. Chance1, J. D. Glickson1, G. Zheng1 1University of Pennsylvania, Philadelphia, PA, 2Huazhong University of Science and Technology, Wu Han, CHINA, 3Shang Hai University, Shang Hai, CHINA. Targeted photodynamic therapy (PDT) is a promising new modality for cancer treatment. Many tumors overexpress low-density lipoprotein LDL receptors (LDLrs) due to increased requirement of cholesterol for membrane synthesis, therefore LDL can be used as an anticancer agents carrier. Neutral chlorophyll dye attached to cholesterol fatty acid esters was synthesized and reconstituted into the lipid core of LDL (Pyro-CE-LDL). 3nmol/g of Pyro-CE-LDL was intravenously injected into HepG2 tumorbearing mouse, which was known to overexpress LDLrs. PDT was carried out using a KTP YAG pumped dye module tuned to produce 670nm light. The light was delivered at a fluorescence rate 150mw/cm2 to a total dose of 300J/cm2. Tumor tissue was scanned by 3-D surface fluorometric scanner for oxidized (Fp), reduced (PN) flavoprotein signals and for Pyro-CE fluorescence. We observed increased Fp signal and decreased PN signal in the PDT treated sample, which resulted in the significantly increased redox ratio. The ratio of Fp/(Fp+PN) represents the redox state of the mitochondrial NAD/NADH redox couple, therefore, can be used to evaluate the PDT damage to the tumor mitochondria. Pyro-CE signal matched very well with the increased redox ratio spot. For the light control sample, no Pyro-CE signal could be detected, and no effect on the Fp and PN signals, which clearly indicated that the PDT response was due to Pyro-CE-LDL photosensitization. In conclusion, with 720nm emission, Pyro-CE-LDL can be used as a tumor selective near infrared fluorescence imaging probe and as a specific PDT agent for the LDLrs overexpressed tumor model. No. 111 DIFFERENTIAL 3’-[18F]FLUORO-3’-DEOXYTHYMIDINE AND 2-DEOXY-2-[18F]FLUORO-D-GLUCOSE UPTAKE IN MURINE MODELS OF HUMAN SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK B. J. Lopresti1, S. M. Thomas2, C. A. Mathis1, N. S. Mason1, J. A. Ruszkiewicz1, J. R. Grandis2 1University of Pittsburgh Dept. of Radiology, Pittsburgh, PA, 2University of Pittsburgh Dept. of Otolaryngology, Pittsburgh, PA. Introduction: Imaging squamous cell carcinoma of the head and neck (SCCHN) in animal models with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and 3’-[18F]fluoro-3’-deoxythymidine (FLT) microPET may represent a
valuable investigational tool for evaluating antitumor response to novel therapeutics in terms of tumor metabolism and cell proliferation rates. Methods: SCCHN cell lines 1483 (n = 3) and 22b (n = 4) were injected subcutaneously in athymic nude mice. MicroPET using a Concorde P4 system was performed when tumors grew to be 4-5 mm in diameter. Animals were anesthetized (isoflurane) and injected with 150-200 µCi of either FLT or FDG. Emission data were collected for 90 minutes and standardized uptake value (SUV) in tumors determined. Each animal was scanned twice, once with each radiotracer, on subsequent days. Results: Uptake of FDG was greatest in heart and brain and elevated in other peripheral tissues. No increase in FDG uptake was observed in 22b (SUV = 1.04 ± 0.11) or 1483 (SUV = 0.97 ± 0.08) tumors. No significant increase in FLT uptake in 22b tumors was observed (SUV = 1.09± 0.16), while 1483 cell tumors showed substantially elevated uptake of FLT (SUV = 2.08 ± 0.39; range: 1.8 - 2.8). Time-activity curves following FLT injection show constant accumulation in tumor, negligible uptake in brain, and an otherwise uniform distribution. Conclusion: FDG uptake in 22b and 1483 tumors was relatively low. Uptake of FLT was elevated in 1483 tumors, but not 22b’s. A similar characterization of other xenografted SCCHN cell lines is ongoing. No. 112 POSITRON EMISSION TOMOGRAPHY IMAGING OF CONSTITUTIVE PERIPHERAL BENZODIAZEPINE RECEPTOR EXPRESSION IN RAT BRAIN USING [C-11]DAA1106 : COMPARISON WITH [C-11]PK-11195 B. J. Lopresti1, N. S. Mason1, S. Kendro1, C. A. Mathis1, T. Suhara2, J. Maeda2, S. Venneti3, C. A. Wiley3 1University of Pittsburgh Dept. of Radiology, Pittsburgh, PA, 2National Institute of Radiological Sciences, Chiba, JAPAN, 3University of Pittsburgh Dept. of Pathology, Pittsburgh, PA. Introduction: Neuroinflammatory responses to central nervous system (CNS) insults may trigger significant upregulation of peripheral benzodiazepine receptor (PBDR) expression on intrinsic activated microglia and infiltrated macrophages. in vivo positron emission tomography (PET) investigations using [C-11]1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinoline carboxamide ([C-11]PK-11195) have demonstrated increased binding in several neurodegenerative and autoimmune diseases. However, low brain uptake and high non-displaceable binding have complicated quantitative analyses. DAA1106 (N-(2,5-dimethoxybenzyl)-N-(5fluoro-2-phenoxyphenyl)acetamide) is a potent (KD = 0.12 nM) and selective PBDR agonist which, labeled with carbon-11, is a promising PET PBDR radioligand with many superior imaging properties. The purpose of this study was to demonstrate specific and reversible binding of [C11]DAA1106 to constitutive levels of PBDR sites in rat brain. Methods: Rats (n=3) were anesthetized (isoflurane) and positioned in a microPET P4 scanner to simultaneously image brain and lungs. The lungs contain a high density of PBDR sites and primarily reflect the kinetic behavior of specific binding. Rats were injected with either [C-11]DAA1106 or [C-11]PK11195 (750 -1500 µCi) and emission data collected for 60 minutes. At 15 minutes post-injection, a displacing dose of unlabeled DAA1106 (1.0 mg/kg) was administered for 60 seconds. Results: [C-11]DAA1106 radioactivity was rapidly and effectively displaced for 10 minutes by unlabeled DAA1106 in both lungs (-92%) and brain (- 75%). [C-11]PK-11195 radioactivity was displaced by unlabeled DAA1106 in lung (- 55%), but not brain (+ 24%). Conclusion: [C-11]DAA1106 kinetics in normal rat brain are analogous to those in lung and are dominated by specific binding while [C-11]PK11195 normal brain kinetics are not.