Publications

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    ABSTRACT: Objective: The aim of our study was to determine the role of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) and indium-111 Octreotide single photon emission tomography ((111)In-Octreotide SPECT) in the evaluation of metastatic medullary thyroid carcinoma (MMTC). Methods: Twenty-five MMTC patients were retrospectively evaluated. All patients had undergone whole-body (18)F-FDG-PET/CT including 20 who had also undergone (111)In-Octreotide SPECT within a maximum interval of 6 weeks. Diagnostic contrast-enhanced computed tomography (CT) alone or as part of (18)F-FDG-PET/CT examination was performed in all patients. Results: Contrast-enhanced CT detected a total of 131 lesions including 79 enlarged lymph nodes and 14 bone lesions. (18)F-FDG-PET/CT visualized a total of 92 true positive lesions (SUVmax range 1.1-10.0, mean 4.0 ± 1.7) including 66 lymph nodes, 7 of which were not enlarged on CT, and 8 bone metastases. In the 20 patients studied with both techniques, a total of 64 and 46 true positive lesions were detected by (18)F-FDG-PET/CT and (111)In-Octreotide SPECT, respectively. In particular, (18)F-FDG uptake was found in 43 lymph nodes and in 7 bone metastases whereas (111)In-Octreotide uptake was detected in 27 lymph nodes and in 10 bone metastases. Conclusions: In MMTC patients, (18)F-FDG-PET/CT provides a useful contribution mainly in evaluating lymph node involvement whereas (111)In-Octreotide SPECT can contribute to the detection and somatostatin receptor characterization especially of bone lesions.
    Full-text · Article · Jan 2016 · Annals of Nuclear Medicine
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    ABSTRACT: Leptomeningeal infiltration of the brain or spinal cord by neoplastic cells may occur as complication of solid or hematopoietic tumors such as non-Hodgkin lymphoma. Previously rare, this event is becoming increasingly common as newer therapies can prolong survival but may not achieve therapeutic concentration in the central nervous system. Although prognosis is poor, early diagnosis and aggressive treatment may lead to prolonged survival and/or improvement of quality of life. We report a case of a 69-year-old man with leptomeningeal infiltration by non-Hodgkin lymphoma revealed by F-FDG-PET/CT and confirmed by subsequent spinal MRI and cerebrospinal fluid cytology.
    No preview · Article · Nov 2015 · Clinical nuclear medicine
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    ABSTRACT: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome predisposing to many endocrine and neuroendocrine tumors (NET). Conventional imaging (CI) cannot provide satisfactory results for all the different types of MEN1-related tumors. Objective of this prospective observational study was to evaluate the role of (68)Ga-DOTATATE PET/CT in MEN1 compared to CI. Diagnostic performance of (68)Ga-DOTATATE PET/CT for the detection of NET was evaluated as well as the prognostic role of SUVmax. Eighteen patients with genetically confirmed MEN1 were evaluated by (68)Ga-DOTATATE PET/CT, endoscopic ultrasounds, multidetector-row computed tomography, magnetic resonance imaging, and hormone/markers serum measurements. Four MEN1-related tumor sites (pancreas, pituitary, parathyroids, adrenals) were considered. Sensitivity and specificity of (68)Ga-DOTATATE PET/CT for the detection of NET were calculated. There was (68)Ga-DOTATATE PET/CT uptake in 11/11 patients with pancreatic lesions, in 9/12 with pituitary adenoma, in 5/15 with parathyroid enlargements, and in 5/7 with adrenal lesions. (68)Ga-DOTATATE PET/CT showed sensitivity and specificity of 100 and 100 % in pancreas, 75 and 83 % in pituitary, 28 and 100 % in parathyroids, and 62.5 and 100 % in adrenals, respectively. Compared with CI, no significant difference in sensitivity for pancreas, pituitary, and adrenals was found, while CI had a better sensitivity for parathyroids (p = 0.002). On the ROC analysis, progression of pancreatic lesions was significantly associated to SUVmax <12.3 (p < 0.05). (68)Ga-DOTATATE PET/CT is greatly helpful in the work-up of MEN1 providing a panoramic view of MEN1-related lesions. There is also a prognostic role of (68)Ga-PET in patients with MEN1-pancreatic lesions.
    Full-text · Article · Aug 2015 · Endocrine
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    ABSTRACT: One of the hallmarks of cancer cells is the excessive conversion of glucose to lactate under normoxic conditions, also known as Warburg effect. Here we tested whether the targeted inhibition of EGFR may revert this effect and reactivate mitochondrial oxidative phosphorylation in non-small cell lung cancer (NSCLC). Sensitive (HCC827) and resistant (H1975 and H1993) NSCLC cells were treated with a panel of EGFR or MET inhibitors and then tested for changes of EGFR signaling, glycolytic cascade and mitochondrial function. Silencing of key glycolytic enzymes was then performed with targeted siRNAs. Furthermore, tumor-bearing nude mice treated with EGFR inhibitors were evaluated with 18F-FDG PET/CT and tumors were analyzed for glycolytic and mitochondrial proteins. Effective inhibition of EGFR signaling in NSCLC cells induced a dramatic reduction of hexokinase II (HKII) and phospho-pyruvate kinase M2 (p-PKM2, Tyr105) levels as well as an upregulation of mitochondrial complexes subunits (OXPHOS). Accordingly, a decreased lactate secretion and increased intracellular ATP levels were also observed in response to EGFR inhibitors. Down-regulation of HKII and PKM2 by targeted siRNA transfection did not cause upregulation of OXPHOS but enhanced the effects of EGFR TKIs. Conversely, selective inhibition of AKT and ERK1/2 caused OXPHOS upregulation and glycolysis inhibition, respectively. Similar findings were obtained in tumors from animals treated with appropriate EGFR inhibitors. Our findings indicate that EGFR inhibitors may reactivate oxidative phosphorylation of cancer cells and provide a mechanistic clue for the rational combination of agents targeting EGFR-dependent proliferation and glucose metabolism in cancer therapy. Copyright © 2015, American Association for Cancer Research.
    No preview · Article · Jul 2015 · Clinical Cancer Research
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    ABSTRACT: To assess whether performing routinely 2-deoxy-2-[(18)F]fluoro-D-glucose PET/CT ((18)FDG PET/CT) scan from the upper thigh to the vertex of skull is clinically relevant. 3502 (1634 female; mean-age 60+16) consecutive patients undergoing (18)FDG PET/CT were retrospectively analyzed. Patients were divided in 10 groups according to primary malignancy. Chi-square analysis was used to assess differences among proportions. A p value < 0.05 was considered significant. (18)FDG PET/CT was positive in head district in 130/3502 (3,7%) patients. In all patients lesions were unknown before PET/CT examination. PET/CT showed 158 positive brain/head uptake in the 130 patients. The 158 lesions were localized in: brain (43/158; 27%), bone (52/158; 33%), lymph node (1/158; 0,6%), soft tissue (55/158; 35%) and other sites (7/158; 4,4%). According to each group, patients were positive in the head district in 1.0% for Gastrointestinal Cancer (7/690), 3.0 % for Genitourinary Cancer (3/101), 3.7 % for Haemathologic Cancer (59/1590), 2.7 % for Gynaecologic Cancer (3/112), 7.8% for Head-Neck-Thyroid and Parathyroid Cancer (26/331), 3.5% for Breast Cancer (7/200), 2.6% for Lung Cancer (7/271), 3.4% for Melanoma (2/59), 7.4% for Sarcoma (2/27), 11.6% for Unknown Primary Tumour (14/121). Our data show a relatively high incidence of brain/head lesion in patients with Unknown Primary Tumour.
    Full-text · Article · Feb 2015
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    ABSTRACT: The aim of this study was to compare the relative contribution of F-FDG PET/CT, Tc-MIBI, and MRI in predicting progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM) patients. Thirty-three newly diagnosed MM patients had been evaluated in a previous study by F-FDG PET/CT, Tc-MIBI, and spine and pelvis MRI reporting focal lesions and diffuse bone marrow involvement. Twenty-seven patients were then subjected to a mean follow-up period of 58 months, whereas 6 patients were lost. F-FDG PET/CT, Tc-MIBI, and MRI were positive in 26, 24, and 22 patients, respectively, showing diffuse bone marrow involvement in 12, 21, and 17 patients and a total of 185, 56, and 39 focal lesions, respectively. At follow-up, 18 patients showed complete or partial remission, whereas 9 patients developed progressive disease, 7 of which died of myeloma. Univariate and subsequent multivariate analysis showed that F-FDG PET/CT focal uptake and Tc-MIBI focal and diffuse uptake predicted PFS (P = 0.0006), whereas F-FDG PET/CT focal uptake and Tc-MIBI focal uptake predicted OS (P = 0.0010). Although MRI diffuse pattern predicted PFS at univariate analysis (P = 0.0376), it was not retained in the model at multivariate analysis. Receiver operating characteristic curve analysis showed that the number of focal lesions best discriminating for PFS and OS prediction was 4 and 11 for F-FDG PET/CT and 2 in both cases for Tc-MIBI, respectively. By Kaplan-Meier analysis and log-rank testing, PFS and OS at follow-up were significantly better in patients showing a number of focal lesions at F-FDG PET/CT or Tc-MIBI lower than the respective cutoff (P = 0.03, P = 0.004, and P < 0.0001, respectively). Finally, PFS was significantly better in patients showing absent/faint diffuse Tc-MIBI uptake than in those having moderate/intense diffuse uptake (P = 0.0012). F-FDG PET/CT and Tc-MIBI may be useful in predicting PFS and OS in myeloma patients.
    Full-text · Article · Jan 2015 · Clinical Nuclear Medicine
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    ABSTRACT: The aim of this study was to evaluate the role of F-FDG PET/CT performed after surgery but before radioiodine therapy in patients with differentiated thyroid cancer. FDG PET/CT was performed off L-thyroxine in 60 newly diagnosed differentiated thyroid cancer patients. Clinical and hematological evaluation as well as high-resolution neck ultrasound were performed. All patients underwent a complete follow-up (range, 6-67 months; mean [SD], 31.7 [20.6] months). The date of recurrence or the most recent office visit was recorded. Progression-free survival (PFS) is the primary end point of this study. Analysis was performed by Cox proportional hazards model. Survival curves were generated using Kaplan-Meier estimates, and the log-rank test was used to assess significance. FDG PET/CT was negative in 63% of patients, 20% had FDG thyroid bed uptake, 5% distant metastases, and 12% lymph node FDG uptake. In patients with positive FDG PET/CT scan (ie, those with distant metastases or lymph node uptake), a higher rate of recurrence was observed (50% vs 6%, P < 0.05). Thyroglobulin, neck ultrasound, stage, and FDG PET/CT correlated with PFS at univariate analysis. At multivariate analysis, only thyroglobulin and FDG PET/CT continued to be predictors of PFS. Patients with a negative FDG PET/CT scan have a better PFS either in the whole group or in those with elevated thyroglobulin level (both >2 ng/mL and >10 ng/mL). FDG PET/CT was abnormal in 17% of patients. Moreover, FDG PET/CT has an independent prognostic role, with a better PFS in patients with a negative scan.
    Full-text · Article · Dec 2014 · Clinical Nuclear Medicine
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    ABSTRACT: Purpose: MET amplification is one of the mechanisms underlying acquired resistance to EGFR tyrosine kinase inhibitors (TKI) in non-small cell lung cancer (NSCLC). Here, we tested whether 3'-deoxy-3'-[(18)F]-fluorothymidine ([(18)F]FLT) positron emission tomography/computerized tomography (PET/CT) can detect MET-mediated resistance to EGFR TKIs and monitor the effects of MET inhibitors in NSCLC. Experimental design: H1993 and H820 NSCLC cells with high and low levels of MET amplification, respectively, and HCC827-expressing MET, but without gene amplification, were tested for the effects of MET inhibitors on the EGFR pathway and proliferation both in vitro and in vivo. Nude mice bearing NSCLCs with and without MET amplification were subjected to [(18)F]FLT PET/CT before and after treatment with crizotinib or erlotinib (50 mg/kg and 100 mg/kg p.o. for 3 days). Results: H1993 cells showed high responsiveness to MET inhibitors and were resistant to erlotinib. Conversely, HCC827 cells showed high sensitivity to erlotinib and were resistant to MET inhibitors. Accordingly, H1993 tumors bearing MET amplification showed a mean reduction in [(18)F]FLT uptake of 28% and 41% after low- and high-dose treatment with crizotinib for 3 days, whereas no posttherapy changes of [(18)F]FLT uptake were observed in HCC827 tumors lacking MET amplification. Furthermore, a persistently high [(18)F]FLT uptake was observed in H1993 tumors after treatment with erlotinib, whereas HCC827 tumors showed up to 39% reduction of [(18)F]FLT uptake following erlotinib treatment. Imaging findings were confirmed by Ki67 immunostaining of tumor sections. Conclusions: [(18)F]FLT PET/CT can detect MET-mediated resistance to EGFR TKIs and its reversal by MET inhibitors in NSCLC.
    Full-text · Article · Jul 2014 · Clinical Cancer Research
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    ABSTRACT: Advancing knowledge of non-small cell lung cancer (NSCLC) has provided new treatment options based on the specific gene alterations found in individual tumors. The presence of activating mutations in the epidermal growth factor receptor (EGFR) in NSCLC is strongly associated with a high sensitivity to EGFR tyrosine kinase inhibitors (TKIs) and is also a criterion used to identify candidates for first-line therapy with these drugs among patients with advanced disease. However, acquired resistance to EGFR TKIs invariably emerges over time due in part to secondary mutations in EGFR or redundant lateral signaling. Molecular imaging, allowing the visualization of cellular processes and their modulation by both conventional anticancer drugs and molecularly targeted agents, may be effectively used in NSCLC patients during treatment with EGFR TKIs. In particular, positron emission tomography with 18F-FDG and 18F-FLT has been performed in both preclinical and clinical settings to distinguish treatment-sensitive from treatment-resistant NSCLCs. Here we provide a short overview of the mechanisms underlying sensitivity and resistance of NSCLCs to EGFR TKIs and then focus on the contribution that molecular imaging can make to the development of tailored therapy in NSCLC patients.
    Full-text · Article · Feb 2014

  • No preview · Conference Paper · Oct 2013
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    ABSTRACT: Purpose: This study aimed to test the role of combined imaging with 18F-FDG-PET/CT and 111In-octreotide SPECT in characterizing thymic epithelial tumors (TETs). Methods: We evaluated 20 patients with newly diagnosed TETs who had undergone concomitant 18F-FDG-PET/CT and 111In-octreotide SPECT. Thymic epithelial tumors were classified by World Health Organization (WHO) as low-risk thymomas (5), high-risk thymomas (4), and thymic carcinomas (11, among which 6 neuroendocrine tumors). Patients were staged according to Masaoka system. 18F-FDG-PET/CT was performed and SUV(max) of primary tumors was recorded. 111In-octreotide SPECT of the thorax was performed, and tumor-to-background ratio was determined on the 24-hour coronal sections. Results: All patients showed increased 18F-FDG uptake in mediastinal lesions. SUV(max) were significantly correlated with WHO classification (r = 0.66, P < 0.01) and with Masaoka stage (r = 0.60, P < 0.01). SUV(max) of low-risk thymomas (mean [SD], 2.87 [0.83]) were significantly lower than those of high-risk thymomas (mean [SD], 7.21 [1.73], P < 0.01) and of thymic carcinomas (mean [SD], 9.39 [5.80], P < 0.05), whereas no significant difference was found between high-risk thymomas and thymic carcinomas. SUV(max) of all high-risk thymomas and thymic carcinomas was 4.5 or greater. All primary tumors were detected by In-octreotide SPECT, and tumor-to-background ratios ranged between 1.67 and 10.10. No statistically significant correlation was found between tumor-to-background ratios and WHO classification (r = 0.24, P = 0.36) and Masaoka stages (r = 0.31, P = 0.23). However tumor-to-background ratios of thymic neuroendocrine tumors (mean [SD], 5.71 [3.09]) were significantly higher than those of all other TETs with SUV(max) of 4.5 or greater (mean [SD], 2.41 [0.56]; P < 0.05). Conclusions: 18F-FDG-PET/CT scan allows to differentiate high-risk epithelial tumors and thymic carcinomas from low-risk thymomas, whereas 111In-octreotide SPECT may identify neuroendocrine tumors among those showing high 18F-FDG uptake.
    Full-text · Article · Mar 2013 · Clinical nuclear medicine
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    ABSTRACT: Background: Brown adipose tissue (BAT) was considered essentially nonexistent in adults until recent evidence obtained using 18-fluorodeoxyglucose (18-FDG) positron emission tomography/computed tomography. It seems to play a role in whole body metabolism, but it has not been evaluated in underweight conditions, such as in young females with constitutional leanness (CL) or anorexia nervosa (AN). Subjects and methods: Thirty-eight subjects were evaluated from October 2011 to March 2012 : 7 CL (21.7 ± 3.6 y, body mass index [BMI] 16.2 ± 1.0 kg/m(2)), 7 AN (23.4 ± 4.5 y, BMI 15.5 ± 0.8), 3 of the 7 AN after stable refeeding (R-AN, 21.3 ± 1.5 y, BMI 18.8 ± 1.1), and 24 normal weight (NW) women (25.6 ± 3.9 y, BMI 22.2 ± 1.5). Fasting resting metabolic rate and respiratory quotient were measured by indirect calorimetry, body composition by bioimpedentiometry (only in CL, AN, and refed AN), and BAT activity by 18-FDG positron emission tomography/computed tomography scan, all in standardized conditions. Results: All CL (100%), none of the AN and refed AN (0%), and 3 of the 24 NW (12%) subjects showed FDG uptake. Average FDG maximum standardized uptake value was 11.4 + 6.7 g/mL in CL and 5.5 ± 1.2 g/mL (min 3.7, max 8.3) in the 3 NW subjects. In CL, the maximum standardized uptake value was directly correlated to resting metabolic rate, corrected for fat-free mass, and inversely correlated with respiratory quotient. Conclusion: BAT activity has been shown in CL in resting thermoneutral conditions and may exert a role against adipose tissue deposition.
    Full-text · Article · Feb 2013 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Unlabelled: (18)F-FDG PET/CT allows the direct measurement of metabolic tumor burden in a variety of different malignancies. The aim of this study was to assess whether metabolic tumor volume (MTV) determined by (18)F-FDG PET/CT could be used in the prediction of progression-free and overall survival in multiple myeloma patients. Methods: Forty-seven patients (18 women, 29 men; mean age ± SD, 63 ± 11 y) with stage IIIA disease who had undergone whole-body (18)F-FDG PET/CT were retrospectively evaluated. Images underwent a 3-dimensional region-of-interest analysis including all focal lesions with a maximum standardized uptake value > 2.5. The MTV of each lesion was calculated using an automated contouring program based on the standardized uptake value and developed with a threshold of 40% of the maximum standardized uptake value. The total MTV of each patient was defined as the sum of metabolic volume of all focal lesions. Patients were treated and then subjected to a mean follow-up period of 24 mo. Results: In the 47 patients studied, MTV range was 1.3-316.3 mL, with a median of 23.7 mL. A direct, significant correlation was found between MTV and the percentage of diffuse infiltration of bone marrow by plasma cells (r = 0.46, P = 0.006), whereas hemoglobin levels were inversely correlated with MTV (r = -0.56, P = 0.0001). At follow-up, patients who developed progressive disease (n = 18) showed a significantly higher MTV (74.7 ± 19.3 vs. 29.8 ± 5.1 mL, P = 0.009) than patients without progressive disease (n = 29). Furthermore, patients who died of myeloma (n = 9) had a significantly higher MTV (123.2 ± 30.6 vs. 28.9 ± 4.2 mL, P = 0.0001) than survivors (n = 38). No differences in age, plasma cell infiltration, M protein, albumin, β2-microglobulin, performance status, International Staging System score, and presence or absence of a bone marrow transplant were found between groups. The MTV cutoff level was determined by receiver-operating-characteristic curve analysis, and the best discriminative value found for predicting progression-free and overall survival was 42.2 and 77.6 mL, respectively. By Kaplan-Meier analysis and log-rank testing, progression-free and overall survival at follow-up were significantly better in patients showing an MTV lower than the cutoff than in those having an MTV higher than the cutoff (χ(2) = 3.9, P = 0.04, and χ(2) = 56.3, P < 0.0001, respectively). Conclusion: The direct measurement of tumor burden obtained by calculating MTV on (18)F-FDG PET/CT images may be used in the prediction of progression-free and overall survival in myeloma patients.
    Full-text · Article · Oct 2012 · Journal of Nuclear Medicine
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    ABSTRACT: Context: Radioactive iodine is a crucial tool for treatment of differentiated thyroid cancer (DTC). In 5% of cases, DTCs lose I-131 avidity and assume an aggressive behaviour. Treatment options for iodine-refractory DTC are limited. We report the experience of off-label use of the tyrosine kinase inhibitor sorafenib for treatment of advanced iodine-refractory DTC. Design: Patients with progressive DTC refractory to radioactive iodine were treated with sorafenib used off-label independently from their performance status. Primary study end-points were radiological response, progression-free survival (PFS) and safety. Secondary end-points were site-specific radiological response and overall survival (OS). An exploratory analysis of the role of serum thyroglobulin (Tg) and fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed. Results: A total of 17 patients were included in the study. Median follow-up was 15·5 months. Clinical benefit was obtained in 71% of subjects (30% partial response and 41% stable disease). Sorafenib was mostly well tolerated, but a high incidence of fatal events was reported (three patients died from severe bleeding events and two from cardiac arrest). Median PFS was 9 months. Median OS was 10 months. The best responses were observed in lymph nodes and lung. Baseline Tg levels and the Tg response to treatment were correlated to both radiological response and PFS. Baseline FDG-PET assessment and early FDG-PET response were correlated to radiological response. Conclusions: Sorafenib allows morphological disease control in the majority of patients with iodine-refractory DTC. Progression-free survival and overall survival were lower than in previous studies as a consequence of the worse clinical condition of our patients. Sorafenib is mostly well tolerated but could have been responsible for the reported fatal events. Baseline Tg and the Tg response to treatment could be useful for predicting morphological response and clinical outcome. Early FDG-PET response could be helpful for the timely identification of nonresponding patients.
    Full-text · Article · Sep 2012 · Clinical Endocrinology
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    ABSTRACT: The identification of genetic and biochemical mechanisms underlying tumor growth and progression along with the unraveling of human genoma provided a plethora of new targets for cancer detection, treatment and monitoring. Simultaneously, the extraordinary development of a number of imaging technologies, including hybrid systems, allowed the visualization of biochemical, molecular and physiological aberrations linked to underlying mutations in a given tumor. In vivo evaluation of complex biological processes such as proliferation, apoptosis, angiogenesis, metastasis, gene expression, receptor-ligand interactions, transport of substrates and metabolism of nutrients in human cancers is feasible using PET/CT and radiolabeled molecular probes. Some of these compounds are in preclinical phases of evaluation whereas others have been already applied in clinical settings. Here we provide prominent examples on how some biological processes and target expression can be visualized by PET/CT in animal tumor models and cancer patients for the noninvasive detection of well-known markers of tumor aggressiveness, invasiveness and resistance to treatment and for the evaluation of tumor response to therapy.
    No preview · Article · Jul 2010 · Contrast Media & Molecular Imaging
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    Preview · Article · Sep 2009 · Journal of Nuclear Medicine
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    ABSTRACT: Multidrug resistance remains the primary cause of treatment failure in cancer patients. Among the multiple cellular mechanisms underlying the resistant phenotype, the enhanced efflux of anticancer drugs mediated by members of the ATP-binding cassette family of transporters such as P-glycoprotein (Pgp) and the reduced apoptosis due to dysregulation of the process are the most common causes of drug resistance. Here we report the results of our studies on the possibility to detect in vivo and non-invasively malignant tumors that will become resistant to subsequent therapy using single-photon emission tomography and 99mTc-Sestamibi, a tumor-seeking agent currently used in clinical practice. This tracer is a lipophilic cation that accumulates in mitochondria in response to plasma membrane e mitochondrial membrane potentials. In addition, the tracer is subjected to Pgp-mediated outward transport thus mimicking the kinetic behaviour of anticancer drugs in resistant cells. Our studies showed that both the uptake and efflux mechanisms of 99mTc-Sestamibi can be helpful for the non-invasive assessment of drug resistance in cancer. While an enhanced tracer clearance is an index of Pgp-function, an altered pattern of tracer uptake is associated with an impaired apoptosis due to Bcl-2/Bcl-xL overexpression or unopposed action. In conclusion, molecular imaging of drug resistance is suitable and may provide biological information that can improve the efficacy of individual-tailored therapeutic strategies.
    No preview · Article · Mar 2009 · Minerva Biotecnologica

  • No preview · Article · Oct 2008 · European journal of nuclear medicine and molecular imaging
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    ABSTRACT: To test whether epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) induce detectable signals in tumor cells and whether such signals may reveal alterations of the apoptotic program. Tumor cells were treated with gefitinib or erlotinib and tested for their ability to accumulate 99mTc-Sestamibi, a radiolabeled lipophilic cation that localizes in mitochondria. Then we tested whether Bcl-2 and Bcl-xL alter the pattern of drug-dependent tracer accumulation while reducing tumor cell sensitivity to EGFR TKIs. The mechanism underlying the pattern of tracer accumulation was elucidated. Finally, imaging studies were done in animal models and lung cancer patients before and after treatment with EGFR TKIs using single-photon emission computed tomography and 99mTc-Sestamibi. Gefitinib increases accumulation of 99mTc-Sestamibi in Bcl-2-overexpressing cells and enhances the physical interaction of phosphorylated Bcl-2 with inositol trisphosphate receptor type 3 (IP3R3). Consequently, a relative increase of cytosolic and mitochondrial calcium levels occurs. Similarly, lung cancer cells showed an increase of tracer uptake and an enhanced interaction of Bcl-xL with IP3R3 on exposure to erlotinib concentrations achievable in plasma. The occurrence of these interactions was associated with an enhanced EGFR TKI-induced apoptosis resistance. Posttreatment imaging studies in nude mice bearing control and Bcl-2-overexpressing breast carcinomas showed a high tumor uptake of the tracer whereas baseline studies failed to visualize tumors. Similarly, an enhancement of tracer uptake could be detected in patients with lung cancer treated with erlotinib. EGFR TKIs generate detectable signals by Bcl-2/Bcl-xL modulation of IP3R3 in tumor cells.
    Preview · Article · Sep 2008 · Clinical Cancer Research
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    ABSTRACT: New imaging techniques have been introduced to assess the extent and severity of disease in multiple myeloma (MM) patients. The aim of our study was to compare newer imaging modalities-such as (18)F-FDG PET/CT, (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintigraphy, and MRI-to assess their relative contribution in the evaluation of MM patients at diagnosis. Thirty-three newly diagnosed patients with MM were prospectively studied. Diagnosis and staging were made according to standard criteria. All patients underwent whole-body (18)F-FDG PET/CT, whole-body (99m)Tc-MIBI, and MRI of the spine and pelvis within 10 d, and imaging findings were compared. (18)F-FDG PET/CT was positive in 32 patients (16 focal uptake, 3 diffuse uptake, 13 focal and diffuse uptake), (99m)Tc-MIBI was positive in 30 patients (6 focal, 11 diffuse, 13 focal and diffuse uptake), and MRI of the spine and pelvis was positive in 27 patients (6 focal, 13 diffuse, 8 focal and diffuse uptake). (18)F-FDG PET/CT showed a total of 196 focal lesions (178 in bones and 18 in soft tissues), of which 121 were in districts other than the spine and pelvis, whereas (99m)Tc-MIBI visualized 63 focal lesions (60 in bones and 3 in soft tissues), of which 53 were in districts other than the spine and pelvis. In the spinal and pelvic regions, (18)F-FDG PET/CT detected 75 focal lesions (35 in spine and 40 in pelvis), (99m)Tc-MIBI visualized 10 focal lesions (1 in spine and 9 in pelvis), and MRI detected 51 focal lesions (40 in spine and 11 in pelvis). In whole-body analysis, (18)F-FDG PET/CT performed better than (99m)Tc-MIBI in the detection of focal lesions, whereas (99m)Tc-MIBI was superior in the visualization of diffuse disease. In the spine and pelvis, MRI was comparable to (18)F-FDG PET/CT and (99m)Tc-MIBI in the detection of focal and diffuse disease, respectively. Because myelomatous lesions may often occur out of spinal and pelvic regions, MRI should be reserved to the evaluation of bone marrow involvement of these districts, whereas (18)F-FDG PET/CT can significantly contribute to an accurate whole-body evaluation of MM patients. Finally, whole-body (99m)Tc-MIBI, despite its limited capacity in detecting focal lesions, may be an alternative option when a PET facility is not available.
    Full-text · Article · Mar 2008 · Journal of Nuclear Medicine

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