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T J McCarthy

Publications and source records attributed to T J McCarthy.

At least 19 recordsLinked to original sources
PubMed2007

Positron emission tomography imaging as a key enabling technology in drug development.

The use of positron emission tomography (PET) in drug development has become more common in the pharmaceutical industry in recent years. One of the biggest challenges to gaining acceptance of this technology is for project teams to understand when to use PET. This chapter reviews the usage of PET in drug development in the context of target, mechanism and efficacy biomarkers. Examples are drawn from a number of therapeutic areas, but we also show that the relative penetration of this technology beyond CNS and oncology applications has been relatively small. However, with the increasing availability of PET and development of novel radiotracers it is expected that the utilization will be much broader in future years, with the additional expectation that the use of PET as an efficacy biomarker will also become more evident.

Animals↗
PubMed2002

Positron emission tomography shows that intrathecal leptin reaches the hypothalamus in baboons.

Human obesity may be caused by a resistance to circulating leptin. Evidence from rodents and humans suggests that a major component of this resistance is an impairment in the ability of the blood-brain barrier (BBB) to transport leptin from the blood to the brain. One potential way to bypass the BBB is by administering leptin into the intrathecal (i.t.) space. To be effective, i.t. leptin would have to move caudally from the site of injection, enter the cranium, and reach the hypothalamic arcuate nucleus at the base of the pituitary fossa. However, many substances, especially small, lipid-soluble molecules, do not diffuse far from the site of i.t. injection but are resorbed back into blood. To determine whether i.t. leptin can move caudally, we injected leptin conjugated to diethylenetriaminepentaacetic acid (DTPA) and labeled with (68)Ga (G-Ob) into the lumbar space of three baboons. We also studied unconjugated DTPA labeled with (68)Ga, which did not move up the spinal cord but rapidly appeared in blood after i.t. injection. In contrast, G-Ob steadily moved toward the cranium and had reached the hypothalamus 91 and 139 min after i.t. injection in two baboons. We estimated the concentration of leptin in the hypothalamic region to be at least 8 ng/ml, which is about 40 times higher than cerebrospinal fluid levels in normal weight humans and about 4 times higher than the highest level ever recorded after the peripheral administration of leptin. In a third baboon, the leptin neither moved caudally nor appeared in the blood. We conclude that leptin administered i.t. can reach the hypothalamus in therapeutic concentrations, although there is considerable individual variation.

Animals↗
PubMed2001

Endobronchial transfection of naked viral interleukin-10 gene in rat lung allotransplantation.

BACKGROUND: Recent studies suggest that viral interleukin-10 (vIL-10) suppresses alloimmune response in transplantation. Tissue mRNA expression of inducible nitric oxide synthase (iNOS) and exhaled nitric oxide (NO) levels have been observed to increase in lung allograft rejection. The aims of this study were to examine the feasibility of vIL-10 gene transfer into rat lung allografts and to investigate its effect on subsequent allograft rejection. METHODS: Male Lewis rats (RT1l) underwent left lung transplantation with allografts from Brown Norway rats (RT1n). The donor rats were endobronchially transfected 2 minutes before harvest with 400 microg (group I, n = 5), 600 microg (group II, n = 5), or 800 microg (group III, n = 5) of naked pCMVievIL-10. Group IV (n = 5) animals, serving as control, received 400 microg of naked pCF1-CAT. All recipients were sacrificed on postoperative day 5. Transgene expression of vIL-10 was assessed by both reverse transcriptase-polymerase chain reaction and immunohistochemistry. Allograft gas exchange, exhaled NO level, histologic rejection score, and mRNA expression of graft cyokines were also assessed. RESULTS: Transgene expression of lung graft vIL-10 was detected by both reverse transcriptase-polymerase chain reaction and immunohistochemistry. The iNOS mRNA expression in groups I, II, and III was significantly lower than that of group IV (p < 0.05, analysis of variance). Exhaled NO levels in groups I, II, and III were significantly lower than in group IV (p < 0.01, analysis of variance). There was no significant difference between groups with respect to gas exchange, peak airway pressure, or histologic rejection score. CONCLUSIONS: It appears that endobronchial transfection of naked vIL-10 plasmid in a rat lung allotransplant model is feasible and suppresses lung iNOS mRNA expression and exhaled NO levels. An association between iNOS upregulation and high exhaled NO levels in lung allograft resection was also noted.

Analysis of Variance↗
PubMed2001

Lipid-mediated ex vivo gene transfer of viral interleukin 10 in rat lung allotransplantation.

BACKGROUND: Recent studies suggest that viral interleukin 10 suppresses alloimmune response in transplantation and that cationic lipids are one of the most promising nonviral vehicles for gene therapy. The aim of this study was to examine the effect of ex vivo lipid-mediated viral IL10 gene transfer into rat lung allografts on subsequent rejection. METHODS: Male F344 rats (RT1lvl) underwent left lung transplantation with allografts from Brown Norway rats (RT1n). Allografts were transvascularly transfected 15 minutes after harvest with 5 mL of 1:20-diluted (group 1, n = 7) or 1:40-diluted (group 2, n = 6) GL67-pCMVievIL-10 complex. Group 3 (n = 7), serving as the control group, received 1:40-diluted GL67-pCF1-chloramphenicol acetyltransferase complex. All allografts were preserved for 3 hours at 10 degrees C before transplantation. In all groups recipients were killed on postoperative day 5. Transgene expression of viral interleukin 10 was assessed by means of both reverse transcriptase-polymerase chain reaction and immunohistochemistry. Histologic rejection score, allograft gas exchange, exhaled nitric oxide level, and allograft cytokine mRNA expression were also assessed. RESULTS: Dose-dependent transgene expression of viral interleukin 10 was detected by means of both reverse transcriptase-polymerase chain reaction and immunohistochemistry. Allograft gas exchange (PaO2) in groups 1 (114.06 +/- 61.1 mm Hg) and 2 (108.58 +/- 35.7 mm Hg) was significantly better than that in group 3 (66.4 +/- 8.22 mm Hg; P =.020 and P =.023, respectively). The vascular rejection score in group 1 was significantly lower than that in group 3 (P =.032, Kruskal-Wallis test). Exhaled nitric oxide levels in group 2 (5.150 +/- 6.38 ppb) were significantly lower than those in group 3 (13.517 +/- 10.4 ppb; P =.039). Allograft interleukin 2 mRNA expression levels in group 1 (1.123 +/- 0.23 relative units) were significantly lower than those in group 3 (1.753 +/- 0.71 relative units; P =.038 vs group 3). CONCLUSIONS: Lipid-mediated ex vivo viral IL10 gene transfer into rat lung allografts improved graft gas exchange, reduced histologic rejection scores, downregulated graft interleukin 2 mRNA expression, and reduced exhaled nitric oxide levels by postoperative day 5. These results suggest a therapeutic potential of graft viral IL10 gene transfer as an effective immunosuppressive strategy against lung allograft rejection.

Animals↗
PubMed2000

Exhaled nitric oxide correlates with experimental lung transplant rejection.

BACKGROUND: Increased nitric oxide production accompanies acute lung allograft rejection. Transforming growth factor-beta1 is an immunosuppressive cytokine capable of ameliorating acute rejection. The purpose of this study was to determine whether exhaled nitric oxide (eNO) concentrations correlated with the degree of acute rejection. METHODS: A model of acute lung transplant rejection in the rat was developed, and concentrations of eNO were measured at the time of animal sacrifice. In group 1 (partial immunosuppression), donor lungs were pretreated with transforming growth factor-beta1 before implantation. In group 2 (fulminant acute rejection), no immunosuppression was used. In group 3 (full immunosuppression), recipients received cyclosporine. Group 4 were normal rats. RESULTS: When measured from both lungs, eNO concentrations were 4.97+/-0.68 versus 6.73+/-2.90 ppb for groups 1 and 2, respectively (p = 0.58). When measured selectively from transplanted left lungs, eNO concentrations were 8.61+/-0.97 versus 42.14+/-7.27 ppb, respectively (p<0.001). In groups 3 and 4, eNO concentrations were 1.02+/-0.21 and 1.51+/-0.74 ppb, respectively. CONCLUSIONS: Exhaled nitric oxide is elevated in fulminant acute rejection, is reduced after partial immunosuppression using transforming growth factor-beta1 gene therapy, and is in the normal range in cyclosporine-treated animals. The measurement of eNO correlates with the degree of acute lung allograft rejection and may serve as a noninvasive measure of acute lung transplant rejection in the clinical setting.

Acute Disease↗
PubMed2000

Adenovirus-mediated gene transfer of human interleukin 10 ameliorates reperfusion injury of rat lung isografts.

OBJECTIVE: The objective of this study was to examine the feasibility of human interleukin 10 gene transfer into rat lung isografts and to investigate the effect of gene transfer on subsequent ischemia-reperfusion injury. METHODS: Male F344 rats were divided into 4 groups and underwent left lung isotransplantation. Twenty-four hours before harvest, 5 x 10E9 pfu (group I, n = 6) or 1 x 10E10 pfu (group II, n = 7) of AdRSVhIL-10 was intravenously administered to donor rats. In group I-C (n = 6) and group II-C (n = 6), serving as controls, 5 x 10E9 pfu and 1 x 10E10 pfu of AdCMVLacZ were administered, respectively. Grafts were preserved for 18 hours at 4 degrees C before implantation and assessed 24 hours after reperfusion. Transgene expression of human interleukin 10 was assessed by both reverse transcriptase-polymerase chain reaction and immunohistochemistry. Graft inducible nitric oxide synthase, tumor necrosis factor alpha, intercellular adhesion molecule-1, growth-regulated gene product/cytokine-induced neutrophil chemoattractant-1, and monocyte chemotactic protein-1 mRNA expression were assessed by reverse transcriptase-polymerase chain reaction. Isograft gas exchange, exhaled nitric oxide, and myeloperoxidase activity were also analyzed. RESULTS: Dose-dependent transgene expression was detected by reverse transcriptase-polymerase chain reaction and immunohistochemistry. Arterial PO (2) in groups I (164.72 +/- 85.3 mm Hg) and II (153.19 +/- 113 mm Hg) was significantly higher than in groups I-C (82.37 +/- 19.1 mm Hg) and II-C (77.95 +/- 33.4 mm Hg) (P =.022 and P =.031, respectively). Arterial PCO (2) in group I (33.40 +/- 6.80 mm Hg) was significantly lower than in group I-C (51.23 +/- 11.9 mm Hg) (P =.0096). Myeloperoxidase activity in group II (0.083 +/- 0.031 DeltaOD. min(-1). mg(-1)) was significantly lower than in group II-C (0.117 +/- 0.028 DeltaOD. min(-1). mg(-1)) (P =.044). The inducible nitric oxide synthase mRNA expression in group II (0.627 +/- 0.28) was significantly lower than in group II-C (1.125 +/- 0.63) (P =. 039). CONCLUSION: Adenovirus-mediated human interleukin 10 gene transfer in vivo into lung isografts ameliorates subsequent ischemia-reperfusion injury. This results in improved graft gas exchange, reduced neutrophil sequestration, and down-regulation of graft inducible nitric oxide synthase mRNA expression.

Adenoviridae↗
PubMed2000

Pulmonary angiotensin-converting enzyme (ACE) binding and inhibition in humans. A positron emission tomography study.

Angiotensin-converting enzyme (ACE) inhibition attenuates pulmonary hypertension and delays the development of pulmonary vascular remodeling in animal models. Thus, ACE inhibition might be a useful treatment for primary pulmonary hypertension (PPH). To determine the dose of ACE inhibitor required to specifically block pulmonary ACE in humans, we measured the combined forward rate constant (CFRC) for [(18)F]-fluorocaptopril, which is proportional to the mass of ACE in the lung, using positron emission tomography (PET). In five normal subjects, CFRC was measured twice, 1 wk apart, to assess measurement reproducibility. The CFRC was 0.151 +/- 0.067 for the first measurement and 0.140 +/- 0.060 for the second measurement (p = not significant [NS]). In five normals, CFRC decreased on average 84%, from 0.177 +/- 0.053/s to 0.028 +/- 0.017/s (p < 0.05), after 1 wk ingestion of 5 mg enalapril orally once a day (the scans were performed 24 h after the last medication). Similarly, in five patients with PPH, CFRC decreased on average 76%, from 0.052 +/- 0. 020/s to 0.012 +/- 0.003 (p < 0.01), after 1 wk enalapril, despite much lower baseline values. We conclude that the total mass of pulmonary ACE appears to be significantly reduced in PPH and that only low doses of ACE inhibitors may be needed to block the effects of ACE on vascular remodeling in PPH.

Adult↗
PubMed1999

Response to inhaled nitric oxide in acute lung injury depends on distribution of pulmonary blood flow prior to its administration.

Responses to inhaled nitric oxide (iNO) in acute lung injury (ALI), as evidenced by improvements in oxygenation, are variable. We hypothesized that the effect of iNO may be related to the pre-iNO distribution of pulmonary blood flow (PBF). In the present study we evaluated the effect of iNO on PBF in normal healthy dogs and in a canine model of ALI induced by oleic acid (OA). In Group "OA only" (n = 5), ALI was induced by central venous injection of 0.08 ml/kg OA. In Group "E+OA" (n = 5), hypoxic pulmonary vasoconstriction after ALI was blocked with low-dose endotoxin (15 microg/kg of Escherichia coli endotoxin) administered 30 min before giving the same dose of OA. Measurements of regional PBF and lung water concentration (LWC) using positron emission tomography (PET) and H215O were performed before and after OA or placebo, and then again at concentrations of 10, 40, and 0 ppm iNO. One hundred twenty minutes after OA injury, PaO2/FIO2 fell significantly in Group OA only, from 567 +/- 32 to 437 +/- 67 mm Hg. In these animals, PBF redistributed from the dorsal edematous regions of the lungs to the nondependent zones, thus partially preserving normal ventilation/ perfusion relationships. As in the normal animals, in Group OA only, iNO did not significantly change either PBF or oxygenation. In Group E+OA, the administration of low-dose endotoxin eliminated perfusion redistribution from the dorsal edematous lung regions. As a result, PaO2/FIO2 fell from 558 +/- 70 to 119 +/- 53 mm Hg, a decrease that was significantly greater than that in Group OA only. In Group E+OA, administration of iNO restored perfusion redistribution to a similar level as in Group OA only, which was associated with a significant improvement in PaO2/FIO2, from 119 +/- 53 to 251 +/- 159 (10 ppm iNO), and 259 +/- 165 mm Hg (40 ppm iNO). We conclude that the effect of iNO on oxygenation after ALI depends on the pre-iNO perfusion pattern, which may help explain the variable response to iNO often observed in patients with acute respiratory distress syndrome.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

90-day subchronic toxicity study in rats and mice fed N-methylpyrrolidone (NMP) including neurotoxicity evaluation in rats.

In mice, there were no effects on body weight or food consumption. As observed in rats, mice fed 2,500 or 7,500 ppm exhibited a change in urine coloration which was not associated with morphological changes in cholesterol, triglycerides, calcium, and alkaline phosphatase occurred at 28 days but not 90 days. These changes are thus assessed as being of minor toxicological relevance. Liver weights were elevated in males fed 2,500 or 7,500 ppm and centrilobular hypertrophy was seen in both sexes fed 7,500 ppm. These changes may be regarded as an adaptation process but are clearly related to NMP exposure. Other toxicological endpoints examined were unaffected by NMP. The NOAEL was 3,000 ppm for both sexes of rats based on body weight effects and changes in 3 neurobehavioral parameters (males only) at higher feeding levels. In mice, the NOAEL was 1,000 ppm based on liver responses to higher concentrations.

Animals↗
PubMed1999

Evaluation of 64Cu-ATSM in vitro and in vivo in a hypoxic tumor model.

UNLABELLED: We have evaluated Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM), an effective marker for the delineation of hypoxic but viable tissue, in vitro in the EMT6 carcinoma cell line under varying degrees of hypoxia and compared it with the flow tracer 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (Cu-PTSM) and the hypoxic tracer 18F-fluoromisonidazole (MISO). We have also compared the uptake of Cu-ATSM and Cu-PTSM in vivo and ex vivo in a murine animal model bearing the EMT6 tumor. METHODS: Uptake of 64Cu-ATSM, 64Cu-PTSM and 18F-MISO in vitro into EMT6 cells was investigated at the dissolved oxygen concentrations of 0, 1 x 10(3), 5 x 10(3), 5 x 10(4) and 2 x 10(5) ppm. Biodistribution performed at 1, 5, 10, 20 and 40 min compared 64Cu-ATSM with 64Cu-PTSM in BALB/c mice bearing EMT6 tumors. To determine long-term retention of 64Cu-ATSM, biodistribution was also performed at 1, 2 and 4 h. Ex vivo autoradiography of tumor slices after co-injection of 60Cu-PTSM (60Cu, T1/2 = 23.7 min) and 64Cu-ATSM (64Cu, t1/2 = 12.7 h) into the same animal was performed. RESULTS: After 1 h, 64Cu-ATSM was taken up by EMT6 cells: 90% at 0 ppm, 77% at 1 x 10(3) ppm, 38% at 5 x 10(3) ppm, 35% at 5 x 10(4) ppm and 31% at 2 x 10(5) ppm. 18F-MISO also showed oxygen concentration dependent uptake, but with lower percentages than 64Cu-ATSM. 64Cu-PTSM showed 83%-85% uptake into the cells after 1 h, independent of oxygen concentration. Biodistribution data of 64Cu-ATSM and 64Cu-PTSM showed optimal tumor uptake after 5 and 10 min, respectively (0.76% injected dose (ID)/organ for 64Cu-ATSM and 1.11%ID/organ for 64Cu-PTSM). Ex vivo imaging experiments showed 60Cu-PTSM uniform throughout the EMT6 tumor, but heterogeneous uptake of 64Cu-ATSM, indicative of selective trapping of 64Cu-ATSM into the hypoxic tumor cells. CONCLUSION: Cu-ATSM exhibits selectivity for hypoxic tumor tissue both in vivo and in vitro and may provide a successful diagnostic modality for the detection of tumor ischemia.

Animals↗
PubMed1998

The state of positron emitting radionuclide production in 1997.

Thirty years ago Michel M. Ter-Pogossian and Henry N. Wagner, Jr. wrote an article that was published in Nucleonics on the cyclotron production of isotopes for biomedical research. In this report we use the Nucleonics paper as the framework to relate their predictions to the current state of the art, we have broken this into four key areas; commercially available cyclotrons, costs of operating cyclotron facilities, the emergence of compact accelerators, and the cyclotron production of long-lived radionuclides for therapeutic applications. Companies producing cyclotrons commercially are; General Electric Medical Systems, CTI Cyclotron Systems, EBCO, IBA, NNK/Oxford Instruments, and Japan Steel Works. The majority of these machines are now negative ion systems, which allows the option of dual irradiation of two targets. All have a modular design, which allows the system to be customed to a particular facility's need. Cyclotron facility costs have increased dramatically since 1966. We have determined that the bulk of the increase lies in the costs to establish and staff the facility. Increased regulation by Federal and State organizations has severely impacted operational expenses. The growing demand for PET radiopharmaceuticals in the clinical arena has increased the staffing requirements of the facility. Surprisingly, the costs of cyclotrons have not increased (in terms of real dollars) especially when one considers the much greater sophistication in target design, automation, and computer control that has occurred during this time. Innovative approaches are being taken to develop low energy accelerators that are capable of producing PET isotopes. These are easier to operate and less expensive than commercially available cyclotrons. Although many of these systems have been developed, none have as yet gained commercial recognition. A number of groups have begun to address the production of longer lived isotopes on biomedical cyclotrons. Development of this technology may well help to further progress in targeted radiotherapy. We present an overview of potentially useful isotopes.

Costs and Cost Analysis↗
PubMed1998

Effects of copper and zinc ions on the germicidal properties of two popular pharmaceutical antiseptic agents cetylpyridinium chloride and povidone-iodine.

The effects of copper and zinc ions on the rate of killing of Gram-negative bacterium Pseudomonas aeruginosa, Gram-positive bacterium Staphylococcus aureus and fungal yeast Candida albicans by antiseptic agents cetylpyridinium chloride and povidone-iodine (Betadine) were investigated. In the 48 test cases copper and zinc ions clearly potentiated the antiseptic agents in 28 (58.3%) cases and exhibited an improved (not clear potentiation) activity in 15 (31.3%) cases. In five (10.4%) cases there was no change in the antiseptics' antimicrobial activity. In general zinc potentiated the antiseptic agents more than copper. If an 'improved activity' was the only criterion for this study, then a more rapid antimicrobial effect was observed in 43 out of the 48 test cases, i.e., 90%.

Anti-Infective Agents, Local↗
PubMed1998

Evaluation of in vivo models for studying calcification behavior of commercially available bovine pericardium.

BACKGROUND AND AIM OF THE STUDY: A common frame of reference is essential when attempting to determine if new treatments intended to reduce calcification of bioprostheses are superior to existing processes and products. The aim of this study was to examine calcification behavior for a commercially available pericardial bioprosthesis in subcutaneous and sheep valve models, and to evaluate the importance of appropriate control treatments in comparative studies with proposed new treatments. METHODS: Samples of bovine pericardium were placed subcutaneously under the dorsal skin of weanling rats and juvenile rabbits for 30-, 60- and 90-day intervals. Samples were either commercially available pericardial tissue or tissue processed with phosphate-buffered glutaraldehyde alone. Commercially available pericardial valves were also implanted in the mitral position in juvenile sheep, with elective sacrifice at 20 weeks. Retrieved samples underwent X-ray, histologic and elemental analysis. RESULTS: Commercial samples retrieved from the subcutaneous and sheep models showed similar, minimal calcification behavior on X-ray and histologic slides, whereas pericardium exposed to glutaraldehyde alone demonstrated rapid calcification. CONCLUSIONS: The 90-day subcutaneous rabbit model produced patterns of calcification similar to those in valves explanted from juvenile sheep after 20 weeks. A statistically significant decrease (p < 10(-8)) in calcification was demonstrated for clinical pericardium when compared with pericardium exposed to glutaraldehyde alone in the subcutaneous model. This suggests that subcutaneous models may be a cost-effective, time-efficient means of evaluating and comparing various tissue treatment methods. The rabbit methodology may provide a more accurate prediction of clinical performance, offering a greater degree of sensitivity. These studies also indicate that the commercially available process shows minimal calcification in the commonly used 30-day weanling rat subcutaneous model, contradicting other reported studies that may not accurately represent commercially available processes.

Animals↗
PubMed1997

Structure-activity relationships in the hydrolysis of acrylate and methacrylate esters by carboxylesterase in vitro.

Acrylate esters are important chemicals in the plastics industry, whose toxicity is theorized to involve alkylation of critical cellular nucleophiles via the Michael addition. Carboxylesterase-mediated hydrolysis of acrylates may be a detoxification mechanism as the unsaturated acid produced is not electrophilic under physiological conditions. Using purified porcine liver carboxylesterase, the enzymatic hydrolysis of several acrylate esters was characterized to determine Km and Vmax values for each ester. The Km (microM) and Vmax (nmol/min) values observed for ethyl acrylate were 134 +/- 16 (S.D.) and 8.9 +/- 2.0, respectively. While the Km for ethyl methacrylate was not significantly different, the Vmax 5.5 +/- 2.5, was significantly lower compared with the corresponding value for ethyl acrylate. The Km and Vmax for butyl acrylate were 33.3 +/- 8.5 microM and 1.49 +/- 0.83 nmol/min, respectively, and the corresponding values for its alpha-methyl analog were not significantly different. The Km and Vmax for tetraethyleneglycol dimethacrylate were 39 +/- 15 microM and 2.9 +/- 1.0 nmol/min, respectively. The Vmax for ethyleneglycol dimethacrylate, 6.9 +/- 2.4 nmol/min, was significantly higher than that of the larger bifunctional ester tetraethyleneglycol dimethacrylate, but the Km was not significantly different. These results indicate that alpha-methyl substitution appears to have a minor effect in the enzymatic hydrolysis of acrylates, and suggest that the relative toxicity of acrylates is not due to differences in carboxylesterase-mediated hydrolysis.

Acrylates↗
PubMed1997

Measurement of upregulation of inducible nitric oxide synthase in the experimental autoimmune encephalomyelitis model using a positron emitting radiopharmaceutical.

Excess nitric oxide has been implicated in the pathogenosis of experimental autoimmune encephalomyelitis (EAE) which is an animal model for multiple sclerosis. Positron emission tomography (PET) is an imaging technique that has shown utility for studying enzyme systems in vivo. A positron-labeled inducible nitric oxide synthetase (iNOS) inhibitor has been studied in EAE-affected mice as well as controls. Greater uptake of the radiolabeled inhibitor was observed in the spinal cord of the affected mice than of control mice. Increased uptake was also observed in other organs not previously implicated in this experimental model. The increased uptake of the radiopharmaceutical in this model suggests that this tracer may have the potential for measuring increased levels of iNOS in humans by PET.

Animals↗
PubMed1997

Reactivity of p-[18F]fluorophenacyl bromide for radiolabeling of proteins and peptides.

Radiolabeling of the somatostatin analog octreotide was attempted with p-[18F]fluorophenacyl bromide ([18F]FPB). Following these unsuccessful trials, the reactivity of FPB was studied using benzyl mercaptan, phenyl acetic acid, benzyl alcohol, and benzyl amine as model compounds for amino acid functional groups. Structure and purity of products, relative reactivity of FPB in competition reactions, and radiolabeling experiments are described. In addition, improvement in labeling efficiency of HSA using [18F]FPB was achieved by pretreatment with 2-iminothiolane.

Acetophenones↗
PubMed1997

Application of a novel phenylpiperazine formation reaction to the radiosynthesis of a model fluorine-18-labeled radiopharmaceutical (18FTFMPP).

The labeled serotonin agonist 3-[18F]fluoro-N-(alpha,alpha,alpha-trifluoro-m-tolyl)piperazine (18FTFMPP) was prepared rapidly using the labeling procedure for trifluorotoluenes, [18F]fluoro-for-nitro exchange, followed by an alumina-supported bis-alkylation. After normal-phase HPLC purification, the labeled product was obtained in 20-32% (n = 20) decay-corrected radiochemical yield with a radiochemical purity > 98% and a specific activity of 100 GBq/mumol. The synthesis time including purification was 3 h. The receptor binding affinity of FTFMPP to rat brain membranes was found to be similar to that of the nonfluorinated parent compound (TFMPP). Although TFMPP has been proposed by others as an agent for the imaging of serotonin receptors, only minimal receptor-mediated uptake was observed.

Animals↗