M Pourdehnad

University of Pennsylvania, Filadelfia, Pennsylvania, United States

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Publications (13)39.05 Total impact

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    Full-text · Article · Feb 2005 · Nuclear Medicine and Biology
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    ABSTRACT: Glyburide is a prescribed hypoglycemic drug for the treatment of type 2 diabetic patients. We have synthesized two of its analogs, namely N-[4-[beta-(2-(2'-fluoroethoxy)-5-chlorobenzenecarboxamido)ethyl]benzenesulfonyl]-N'-cyclohexylurea (2-fluoroethoxyglyburide, 8b) and N-[4-[beta-(2-(2'-fluoroethoxy)-5-iodobenzenecarboxamido)ethyl]benzenesulfonyl]-N'-cyclohexylurea (2-fluoroethoxy-5-deschloro-5-iodoglyburide, 8a), and their fluorine-18 labeled analogs as beta-cell imaging agents. Both F-18 labeled compound 8a and compound 8b were synthesized by alkylation of the corresponding multistep synthesized hydroxy precursor 4a and 4b with 2-[(18)F]fluoroethyl tosylate in DMSO at 120 degrees C for 20 minutes followed by HPLC purification in an overall radiochemical yield of 5-10% with a synthesis time of 100 minutes from EOB. The octanol/water partition coefficients of compounds 8a and 8b were 141.21 +/- 27.77 (n = 8) and 124.33 +/- 21.61 (n = 8), respectively. Insulin secretion experiments of compounds 8a and 8b on rat islets showed that both compounds have a similar stimulating effect on insulin secretion as that of glyburide. In vitro binding studies showed that approximately 2% of compounds 8a and 8b bound to beta TC3 and Min6 cells and that the binding was saturable. Preliminary biodistribution studies in mice showed that the uptake of both compounds 8a and 8b in liver and small intestine were high, whereas the uptake in other organs studied including pancreas were low. Additionally, the uptake of compound 8b in vivo was nonsaturable. These results tend to suggest that compounds 8a and 8b may not be the ideal beta-cell imaging agents.
    No preview · Article · Jun 2004 · Nuclear Medicine and Biology
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    ABSTRACT: The association of hyperglycaemia with reduced fluorodeoxyglucose (FDG) uptake by tumour cells is well established. Therefore, it is standard practice that all patients must fast for at least several hours prior to FDG positron emission tomography (PET) imaging. However, the effect of hyperglycaemia on FDG uptake by inflammatory and infectious lesions is unknown. The aim of this study was to investigate this important issue. For in vitro studies human mononuclear cells were isolated from 12 normal volunteers and FDG uptake was determined in medium containing differing concentrations of glucose. FDG uptake by human mesothelioma cells was also measured for comparison. For studies involving patients, 416 FDG PET scans of patients with confirmed malignancy (n=321) or benign lesions (n=95) were reviewed retrospectively. The relationship between serum glucose level and FDG uptake by the lesions was assessed utilizing the standardized uptake value (SUV) technique. In the in vitro studies, while FDG uptake by mesothelioma cells decreased as glucose concentration increased, there was no differential uptake of FDG uptake by mononuclear cells at glucose concentrations less than 250 mg x dl(-1). In clinical patients, FDG uptake by malignant lesions was slightly, but negatively affected by serum glucose level (r= -0.21, P<0.01) (glucose range 49-187 mg x dl(-1)). In contrast, FDG uptake by inflammatory lesions was positively associated with serum glucose level (r=0.43, P<0.01) (glucose range 54-215 mg x dl(-1)). While the degree of FDG uptake is primarily influenced by the nature of the underlying lesion, serum glucose concentration appears to have a small effect on FDG uptake, which differs between malignant disorders and inflammatory processes. Our data suggest that below a certain level, elevated glucose concentration might not have a negative effect on FDG uptake in inflammatory cells, contrary to that observed in malignant disorders.
    No preview · Article · Oct 2001 · Nuclear Medicine Communications
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    ABSTRACT: The aim of this study was to investigate the difference in the rates of FDG uptake between malignant and inflammatory cells and processes. In vitro studies: (18)F-FDG uptake by different tumor cell lines (human mesothelioma [REN]; rat mesothelioma [II45]; mice melanoma [B18F10]; mice mesothelioma [AB12]; human myeloma [GM1500]; and human ovarian cancer [SKOV3]) and peripheral blood mononuclear cells isolated from 8 healthy human volunteers was measured 20 and 60 min after FDG was added into growth medium. Animal studies: II45 cells were implanted into the left flank of rats (n = 5) and a focal inflammatory reaction (mechanical irritation) was generated in the right flank. PET images at 45 and 90 min after injection of FDG were obtained and standardized uptake values (SUVs) were determined. Patient studies: Seventy-six patients who had dual time FDG PET scans were retrospectively analyzed. All results were expressed as the percentage change in SUV of the later time image from that of the earlier time (mean +/- SD). In vitro studies: Except for the SKOV3 cell line, which had only minimally increased FDG uptake (+10% +/- 26%; P > 0.3), all other tumor cell lines tested showed significantly increased FDG uptake over time (GM1500, +59% +/- 19%; B18F10, +81% +/- 15%; AB12, 93% +/- 21%; II45, +161% +/- 21%; REN, +198% +/- 48%; P < 0.01 for all). By contrast, FDG uptake in mononuclear cells was decreased in 7 of 8 donors. Animal studies: SUVs of tumors from 90-min images were significantly higher than those from 45-min images (+18% +/- 8%; P < 0.01), whereas the SUVs of inflammatory lesions decreased over time (-17% +/- 13% of the early images; P < 0.05). Clinical studies: The SUVs of delayed images from the known malignant lesions compared with those of earlier scans increased over time (+19.18% +/- 9.58%; n = 31; P < 0.001; 95% confidence interval, 15.8%-22.6%). By contrast, the SUVs of benign lung nodules decreased slightly over time (-6.3% +/- 8.1%; n = 12; P < 0.05; 95% confidence interval, -10.9% to -1.7%). The SUV of inflammatory lesions caused by radiation therapy (+1.16% +/- 7.23%; n = 8; P > 0.05; 95% confidence interval, -3.9%-6.2%) and the lesions of painful lower limb prostheses (+4.03% +/- 11.32%; n = 25; P > 0.05; 95% confidence interval, -0.4%-8.5%) remained stable over time. These preliminary data show that dual time imaging appears to be useful in distinguishing malignant from benign lesions. Further research is necessary to confirm these results.
    Full-text · Article · Sep 2001 · Journal of Nuclear Medicine
  • F Ponzo · HM Zhuang · FM Liu · M Pourdehnad · NV Ghesani · A Alavi

    No preview · Conference Paper · Aug 2001
  • H Zhuang · M Pourdehnad · A J Yamamoto · M D Rossman · A Alavi
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    ABSTRACT: Fluorine-18 fluorodeoxyglucose (F-18 Fdg) positron emission tomographic (PET) imaging in a 28-year-old immunocompetent man with fever and acute dyspnea showed diffusely increased uptake in both lungs with a maximum standardized uptake value of 8.1. A thoracic computed tomogram showed diffuse ground-glass changes, suggesting either hypersensitivity pneumonitis or pneumocystis infection. Open lung biopsy revealed interstitial infiltrate with noncaseating granulomas, and staining was negative for fungi, acid-fast bacilli, and pneumocystis. The patient was treated with steroids for hypersensitivity pneumonitis and initially improved. One month later, the lung tissue culture grew Mycobacterium avium intracellulare and treatment for that was started.
    No preview · Article · Jun 2001 · Clinical Nuclear Medicine

  • No preview · Article · May 2001 · Journal of Labelled Compounds and Radiopharmaceuticals
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    ABSTRACT: The purpose of this study was to evaluate the feasibility of using 18F-FDG and PET for the detection of infection associated with lower limb arthroplasty. Seventy-four prostheses in 62 patients in whom infection was suspected after artificial hip or knee placement were studied with this technique. Images were obtained 60 min after an intravenous injection of FDG. The images were interpreted as positive for infection if tracer uptake was increased at the bone-prosthesis interface. A final diagnosis was made by surgical exploration or clinical follow-up for 1 y. PET results were compared with the follow-up outcome in all patients. The sensitivity, specificity, and accuracy of PET for detecting infection associated with knee prostheses were 90.9%, 72.0%, and 77.8%, respectively. The sensitivity, specificity, and accuracy of PET for detecting infection associated with hip prostheses were 90%, 89.3%, and 89.5%, respectively. Overall, the sensitivity was 90.5% and the specificity was 81.1% for detection of lower limb infections. FDG PET is a useful imaging modality for detecting infections associated with lower limb arthroplasty and is more accurate for detecting infections associated with hip prostheses than for detecting infections associated with knee prostheses.
    Full-text · Article · Feb 2001 · Journal of Nuclear Medicine
  • H Zhuang · P Sinha · M Pourdehnad · P S Duarte · AJ Yamamoto · A Alavi
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    ABSTRACT: Liver metastasis is a common consequence of colorectal carcinoma. Early and accurate detection of liver metastasis is crucial for a decision about partial hepatectomy, which is considered a standard and potentially curative therapy in such a setting. The presence of extrahepatic metastases will exclude surgical resection as a therapeutic option. Positron emission tomography with fluorine-18-deoxyglucose (FDG-PET) has been successful in detecting and staging a variety of malignancies. The purpose of this study was to assess the utility of FDG-PET in the accurate detection of liver and distal metastases from colorectal cancer. The results of 80 PET and computed tomography (CT) scans were compared with surgical pathology and clinical outcome. FDG-PET detected liver metastases in 28 patients, with a sensitivity of 100%. CT detected metastasis in 20 patients, giving a sensitivity of 71.4%. In addition, in one patient with negative CT findings, PET detected a focus of hypermetabolism in the region adjacent to liver, which was proven to be a second focus of primary colon carcinoma. In six patients with liver metastases, PET correctly detected extrahepatic lesions, while CT only detected hepatic lesions. In conclusion, FDG-PET is an excellent imaging modality for the detection and staging of liver metastases in patients with colorectal carcinomas.
    No preview · Article · Oct 2000 · Nuclear Medicine Communications
  • HM Zhuang · P Duarte · M Pourdehnad · AJ Yamamoto · JC Loman · P Sinha · A Alavi
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    ABSTRACT: Background: In cost-effective analysis regarding to utilization of FDG-PET on lung nodules, most studies focused on lung lesions themselves (benign vs. malignant) and possible metastases if primary lesion is malignant. However, in a patient with pulmonary nodules, abnormal sites of increased FDG uptake on a whole-body PET scan may either the primary tumor or lesions unrelated to lung malignancy. The incidence of detection of the unsuspected lesions, which often changes the management of these patients, should also be included in the cost-effective analysis.Methods: We retrospectively analyzed 213 cases referred for evaluation of pulmonary nodules. 89 of them proved to have lung malignancy and were excluded in our study. None of the remaining 124 patients had prior clinical or radiographic evidence of other abnormalities before undergoing FDG-PET. All unsuspected lesions were verified either histologically or by the clinical course of the disease.Results: Among the 124 patients without lung cancer, FDG-PET revealed unsuspected abnormality in eight patients. These include other malignancy (colon cancer x 3, lymphoma x 1) and benign lesions (sarcoidosis x 3, cystic kidney x 1). None of the 124 patients studied had additional pathology found during follow-up.Conclusion: The routine uses of FDG-PET for characterizing the lung lesions significantly increases the chances detecting unexpected other pathology. The incidental FDG-PET findings of unsuspected lesions, especially those unrelated to lung cancers, no doubt have a major impact on the management of these patients and may prove to be cost-effective.
    No preview · Article · Aug 2000 · Clinical Positron Imaging
  • O Couturier · C Le Rest · J Gournay · M Pourdehnad · B Bridji · A Turzo · Y Bizais
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    ABSTRACT: There is no consensus regarding the best way to estimate the lag phase time (Tlag) and the constant emptying time (TRE) of the gastric emptying of solids. Furthermore, biphasic gastric emptying is usually described by the modified power exponential function of either Elashoff or Siegel. In an attempt to test the validity of the power exponential functions and to identify relevant parameters of biphasic gastric emptying, we followed an approach which consists of describing the power exponential function by two straight lines. The first line is horizontal and represents Tlag. The second line is tangential to the constant emptying [tangent at the maximum slope (MS) or at the half-emptying value]. Scintigraphic data of 132 patients and 15 controls were fitted by both power exponential functions. Each corresponding half-emptying time, Tlag and TRE estimated from the Elashof and Siegel power exponential functions were strongly correlated (0.93 < r < 1, P < 0.0001). The Bland and Altman statistical method demonstrated good agreement (<5% outliers). The half-emptying tangent method sometimes gave negative Tlag and should be abandoned. Tlag(MS) and TRE(MS) did not correlate and therefore were independent parameters. We conclude that the Elashoff and Siegel functions are equivalent and that the maximum slope tangent method allows a reliable description of the two independent phases of gastric emptying.
    No preview · Article · Jul 2000 · Nuclear Medicine Communications
  • K L Teff · A Alavi · JG Chen · M Pourdehnad · R R Townsend
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    ABSTRACT: We compared the vagal contribution to gastric emptying in lean and obese subjects by monitoring gastric emptying of a meal during muscarinic blockade. Lean (n = 6) and obese subjects (n = 6) underwent two treatments: 1) saline infusion and 2) atropine infusion [0.4 mg/m2 bolus, 0.4 mg. (m2)-1. h-1] for 2 h, initiated 30 min before ingestion of a 600-kcal breakfast (64% carbohydrate, 23% fat, 13% protein) composed of orange juice (labeled with Indium-111), egg sandwich (labeled with Technetium-99m), cereal, milk, and banana. Anterior and posterior images were taken every 90 s for 90 min using a dual-headed camera. Atropine significantly delayed emptying of both solid (P < 0.007) and liquid (P < 0.002). Obese subjects exhibited a greater delay in liquid emptying during muscarinic blockade compared with lean subjects (P < 0.02). Female subjects exhibited a slower rate of gastric emptying and were less sensitive to atropine. These data suggest that obese subjects exhibit altered gastric cholinergic activity compared with lean subjects and that gender differences in gastric emptying rate may be due to differences in autonomic tone.
    No preview · Article · Mar 1999 · The American journal of physiology
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    ABSTRACT: The human MHC non-restricted cytotoxic T cell line TALL-104 has potent anti-tumor effects in dogs with spontaneous tumors. This study was designed to examine the effects of the development of host immune responses on the baseline organ distribution of TALL-104 cells in healthy dogs. 111In-oxine labeled TALL-104 cells (107 cells/kg) were infused systemically in three dogs, either on day 1, 3, or 5 of a 5-day injection cycle; two dogs received two more injections of the labeled cells at monthly intervals, whereas the third dog received free 111In-oxine, 3 months after the first 5-day infusion. Analysis of blood and plasma cell clearances and imaging studies indicated a progressively faster clearance of the cells from the blood and organs after multiple daily injections as well as at the time of each monthly boost when host immune responses against the xenogeneic cells had developed. These findings have important therapeutic implications for the design of effective TALL-104 cell administration schedules in clinical trials.
    No preview · Article · Mar 1999 · International Journal of Oncology