M Pourdehnad

University of Pennsylvania, Filadelfia, Pennsylvania, United States

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Publications (15)44.93 Total impact

  • Nuclear Medicine and Biology 02/2005; 32(2):209-209. DOI:10.1016/j.nucmedbio.2004.12.002 · 2.41 Impact Factor
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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.
    Nuclear Medicine and Biology 06/2004; 31(4):483-91. DOI:10.1016/j.nucmedbio.2003.12.003 · 2.41 Impact Factor
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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.
    Nuclear Medicine Communications 10/2001; 22(10):1123-8. DOI:10.1097/00006231-200110000-00011 · 1.37 Impact Factor
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    ABSTRACT: Anterior temporal lobectomy offers a high chance of seizure-free outcome in patients suffering from drug-refractory complex partial seizure (CPS) originating from the temporal lobe. Other than EEG, several functional and morphologic imaging methods are used to define the spatial seizure origin. The present study was undertaken to compare the merits of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), magnetic resonance imaging (MRI) and single-voxel proton MR spectroscopy (MRS) for the lateralization of temporal lobe seizure foci. The clinical charts and imaging data of 43 consecutive CPS patients were reviewed. Based on surface EEG, 31 patients were classified with temporal lobe epilepsy (TLE; 25 lateralized, 6 not lateralized) and 12 with non-temporal lobe epilepsy. All were examined by FDG-PET, MRS and MRI within 6 weeks. FDG-PET and MRI were interpreted visually, while the N-acetyl-aspartate to creatine ratio was used for MRS interpretation. One FDG-PET scan was invalid due to seizure activity post injection. The MR spectra could not be evaluated in five cases bilaterally and three cases unilaterally for technical reasons. A total of 15 patients underwent anterior temporal lobectomy. All showed a beneficial postoperative outcome. When the proportions of agreement between FDG-PET (0.77), MRI (0.58) and MRS (0.56) and surface EEG in TLE cases were compared, there were no significant differences (P>0.10). However, FDG-PET showed a significantly higher agreement (0.93) than MRI (0.60; P=0.03) with the side of successful temporal lobectomy. The concordance of MRS with the side of successful temporal lobectomy was intermediate (0.75). When the results of functional and morphologic imaging were combined, no significant differences were found between the rates of agreement of FDG-PET/MRI and MRS/MRI with EEG (0.80 vs 0.68; P=0.50) and with the side of successful temporal lobectomy (0.87 vs 0.92; P=0.50) in TLE cases. However, MRS/MRI showed significantly more lateralized temporal lobe abnormalities in non-temporal lobe epilepsy cases than FDG-PET/MRI (0.90 vs. 0.17; P<0.01). Although FDG-PET seems to be the most reliable and stable method for this purpose, we conclude that in TLE cases it may be justified to perform MRS, which is less expensive, faster and has no radiation exposure, in combination with MRI before FDG-PET, since FDG-PET offers little additional diagnostic information if MRS and MRI indicate the same seizure focus lateralization.
    European Journal of Nuclear Medicine 10/2001; 28(10):1529-40. DOI:10.1007/s002590100602 · 5.22 Impact Factor
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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.
    Journal of Nuclear Medicine 09/2001; 42(9):1412-7. · 5.56 Impact Factor
  • Congress of the european association of nuclear medicine, Napoli, Italy; 08/2001
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    ABSTRACT: Fluorodeoxyglucose positron emission tomography (FDG PET) has been used extensively to detect and stage various cancers. However, normal variation and inflammatory lesions may lead to false-positive interpretations of PET findings. The authors report three cases of increased pelvic FDG uptake with differing origins. Although the findings are similar, a postpartum uterus, lymphoma, and a bleeding uterus caused pelvic FDG uptake in these patients. Interestingly, of these three patients, the patient with lymphoma had the lowest level of FDG uptake. Clinical correlation is needed for the accurate interpretation of FDG-PET findings.
    Clinical Nuclear Medicine 07/2001; 26(6):515-7. DOI:10.1097/00003072-200106000-00007 · 2.86 Impact Factor
  • Clinical Nuclear Medicine 06/2001; 26(5):458. · 2.86 Impact Factor
  • Journal of Labelled Compounds and Radiopharmaceuticals 05/2001; 44. DOI:10.1002/jlcr.2580440139 · 1.19 Impact Factor
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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.
    Journal of Nuclear Medicine 02/2001; 42(1):44-8. · 5.56 Impact Factor
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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.
    Nuclear Medicine Communications 10/2000; 21(9):793-8. DOI:10.1097/00006231-200009000-00002 · 1.37 Impact Factor
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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.
    Clinical Positron Imaging 08/2000; 3(4):180. DOI:10.1016/S1095-0397(00)00092-3
  • HM Zhuang, P S Duarte, M Pourdehnad, PY Li, A Alavi
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    ABSTRACT: Fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography has been used extensively in the diagnosis of malignant conditions with high rates of sensitivity and specificity. However, increased FDG uptake is not limited to malignant tissue. In general, lesions with a mild degree of FDG uptake as measured by standardized uptake values less than 2.0 are considered benign, whereas those with values greater than 2.5 are usually regarded as malignant. Standardized uptake values in the kidney can be as high as 22 as a result of excretion of FDG through urine. Two cases are reported in which renal abnormalities could not be distinguished from urine based on standard uptake values alone.
    Clinical Nuclear Medicine 06/2000; 25(5):358-60. DOI:10.1097/00003072-200005000-00008 · 2.86 Impact Factor
  • K L Teff, A Alavi, J 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.
    The American journal of physiology 03/1999; 276(3 Pt 2):R707-14. · 3.28 Impact Factor
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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.
    International Journal of Oncology 03/1999; 14(2):233-44. DOI:10.3892/ijo.14.2.233 · 3.03 Impact Factor