Ciro Mainolfi

In vivo detection of multidrug-resistant (MDR1) phenotype by technetium-99m sestamibi scan in untreated breast cancer patients

Technetium-99m sestamibi is a transport substrate recognised by the multidrug-resistant P-glycoprotein (Pgp). To test whether99mTc-sestamibi efflux is enhanced in breast carcinomas overexpressing Pgp, we determined the efflux rates of99mTc-sestamibi and Pgp levels in tumours from 30 patients with untreated breast carcinoma. Patients were intravenously injected with 740 MBq of99mTc-sestamibi and underwent a 15-min dynamic study followed by the acquisition of static planar images at 0.5, 1, 2 and 4 h. Tumour specimens were obtained from each patient 24 h after99mTc-sestamibi scan and Pgp levels were determined using125I-MRK16 monoclonal antibody and in vitro quantitative autoradiography. All breast carcinomas showed high uptake of99mTc-sestamibi and data from region of interest analysis on sequential images were fitted with a monoexponential function. The efflux rates of99mTc-sestamibi, calculated from decay-corrected time-activity curves, ranged between 0.00121 and 0.01690 min−1 and were directly correlated with Pgp levels measured in the same tumours (r=0.62;P<0.001). Ten out of 30 breast carcinomas (33%) contained 5 times more Pgp than benign breast lesions and showed a mean concentration of 5.73±1.63 pmol/g of tumour (group A). The remaining 20 breast carcinomas had a mean Pgp concentration of 1.29±0.64 pmol/g (group B), equivalent to that found in benign breast lesions.99mTc-sestamibi efflux from tumours of group A was 2.7 times higher than that observed in tumours of group B (0.00686±0.00390 min−1 vs 0.00250±0.00090 min−1,P<0.001). The in vivo functional test with99mTc-sestamibi showed a sensitivity and a specificity of 80% and 95%, respectively. In conclusion, the efflux rate of99mTc-sestamibi may be used for the in vivo identification of the multidrug resistant (MDR1) phenotype in untreated breast cancer patients.

Bone mineral density in children, adolescents, and young adults with epilepsy.

Purpose:  The aim of this study was to assess bone mineral density (BMD) in a large population of children, adolescents, and young adults with epilepsy alone or in association with cerebral palsy and/or mental retardation.

Effects of sex steroids on bone in women with subclinical or overt endogenous hypercortisolism

OBJECTIVE Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Nevertheless, limited data are available on bone status in patients with endogenous cortisol excess. This study is aimed at investigating the role of sex steroids and severity of hypercortisolism on bone mineral density (BMD) and prevalence of vertebral fractures in female patients. DESIGN Cross-sectional, case-control study. PATIENTS Seventy-one consecutive women were enrolled: 36 with overt hypercortisolism (26 with ACTH-secreting pituitary adenoma and 10 with cortisol-secreting adrenal tumor) and 35 with subclinical hypercortisolism due to adrenal incidentalomas. They were compared with 71 matched controls. METHODS At diagnosis, we measured serum cortisol, FSH, LH, estradiol, testosterone, androstenedione and DHEAS, and urinary cortisol excretion. BMD was determined by dual energy X-ray absorptiometry at the lumbar spine and femoral neck. Vertebral fractures were investigated by a semiquantitative scoring method. RESULTS Between women with overt and subclinical hypercortisolism BMD values and prevalence of any vertebral (69 vs 57%, P = 0.56), clinical (28 vs 11.4%, P = 0.22), and multiple vertebral fractures (36 vs 31%, P = 0.92) did not differ. Among patients with subclinical hypercortisolism, amenorrhoic women had a lower BMD (P = 0.035) and more frequent vertebral fractures (80 vs 40%; P = 0.043) when compared with the eumenorrhoic ones. Among women with overt hypercortisolism, there was no difference in lumbar BMD (P = 0.37) and prevalence of fractures (81 vs 60%; P = 0.26) between those amenorrhoic and eumenorrhoic. By logistic regression analysis, lumbar spine BMD values and cortisol-to-DHEAS ratio were the best predictors of vertebral fractures (P < 0.01). CONCLUSIONS Vertebral fractures are very common in women with endogenous cortisol excess, regardless of its severity. The deleterious effects of hypercortisolism on the spine may be partly counterbalanced by DHEAS increase at any degree of cortisol excess, and by preserved menstrual cycles in women with subclinical but not in those with overt hypercortisolism.

FGD‐PET in the follow‐up of recurrent colorectal cancer

Objective  The current methods of detection of recurrent colorectal cancer after surgical treatment are inaccurate using conventional imaging. This study set out to detect early recurrence by means of PET in patients treated surgically for colorectal cancer by curative resection.

Excellent prognosis and prevalence of HCV infection of primary hepatic and splenic non-Hodgkin’s lymphoma

Background:  Primary Hepatic (PHL) and Primary Splenic (PSL) non‐Hodgkin’s Lymphoma are rare entities. Small series of PHL and PSL have been reported, suggesting a non‐fortuitous association with Hepatitis C Virus (HCV) infection. The prognosis is believed to be dismal, with early recurrence and short survival.

Combination of docetaxel and cetuximab for penile cancer: A case report and literature review

Guidelines on the treatment of metastatic squamous cell carcinoma of the penis are limited to a few prospective trials. Cisplatin-based regimens represent the standard of treatment with promising activity of taxanes. Recently, epidermal growth factor receptor overexpression has been shown in these patients. We treated an elderly man with a docetaxel–cetuximab combination after failure of the cisplatin regimen. We observed a necrosis of the inguinal lymph nodes and a reduction of 18F-fluorodeoxyglucose uptake at PET/CT scan. Only mild mucositis and skin toxicity had been detected. Our case report, the first in the literature, shows that this combination is active and well tolerated in penile squamous cell carcinoma.

Tc-99m MIBI scintigraphy in patients with lung cancer : Comparison with CT and fluorine-18 FDG PET imaging

Tc-99m MIBI imaging has been used to evaluate patients with different neoplastic disorders, but its role in nuclear oncology has not been definitely established. In this study, we compared the results of Tc-99m MIBI (planar and SPECT imaging) with those of F-18 FDG PET radionuclide studies in 19 patients who had proven lung cancer. One patient was studied in follow-up. All patients underwent chest CT scans. MIBI and FDG images were qualitatively and quantitatively analyzed using region of interest analysis. Quantitative evaluation of MIBI and FDG activities in lung-tumor lesions was performed calculating tumor/nontumor ratios. On CT, 18 lung tumors were detected, while one patient was disease free. For lung lesions, the diagnostic sensitivity of planar MIBI imaging was 83%, while those of MIBI SPECT and FDG PET were both 100%. The quantitative analysis of lung-tumor MIBI and FDG activities showed that FDG uptake was significantly (P < 0.001) higher compared with MIBI uptake (5.5 +/- 3.1 vs 2.1 +/- 0.6); concordant MIBI and FDG images were found in 4 lesions in terms of central activity defect showing central necrotic tumor tissue. For lymph node abnormalities, planar MIBI scan only detected 3 lesions in 3 patients, whereas MIBI SPECT identified 9 lesions in 5 patients. FDG PET showed 13 lymph node abnormalities in 5 patients. This study shows similar results of Tc-99m MIBI SPECT and F-18 FDG PET in the diagnostic evaluation of patients with lung tumors. However, FDG lung tumor uptake was significantly higher compared with MIBI accumulation, suggesting a high glucose tumor metabolism. Thus, MIBI SPECT imaging may be useful to evaluate such patients and may be considered an alternative when PET is not available.

Functional characterization of brain tumors: An overview of the potential clinical value

Early detection and characterization are still challenging issues in the diagnostic approach to brain tumors. Among functional imaging techniques, a clinical role for positron emission tomography studies with [18F]-fluorodeoxyglucose and for single photon emission computed tomography studies with [201Tl]-thallium-chloride has emerged. The clinical role of magnetic resonance spectroscopy is still being defined, whereas functional magnetic resonance imaging seems able to provide useful data for presurgical localization of critical cortical areas. Integration of morphostructural information provided by computed tomography and magnetic resonance imaging, with functional characterization and cyto-histologic evaluation of biologic markers, may assist in answering the open diagnostic questions concerning brain tumors.

Tc-99m tetrofosmin tomography after nitrate administration in patients with ischemic left ventricular dysfunction: Relation to metabolic imaging by PET

Background. In patients with ischemic left ventricular (LV) dysfunction, myocardial perfusion imaging after nitrate administration may improve the identification of dysfunctional but viable myocardium. This study was designed to assess the relationship between tetrofosmin uptake after nitrate administration and metabolic activity as assessed by positron emission tomography (PET) in patients with ischemic LV dysfunction.Methods and Results. Thirty-six patients with chronic myocardial infarction and LV dysfunction (ejection fraction, 35% ± 6%) underwent resting technetium 99m tetrofosmin single photon emission computed tomography (SPECT) imaging under control conditions (baseline) and after sublingual administration of 10 mg isosorbide dinitrate. Within 1 week, all patients underwent metabolic PET imaging with fluorine 18-fluorodeoxyglucose. Tetrofosmin uptake and metabolic activity were measured in 13 segments/patient. Regional LV function was assessed in corresponding segments by echocardiography. On baseline tetrofosmin imaging, 53 (40%) of the 131 akinetic or dyskinetic segments had reduced (<55% of peak activity) tracer uptake. Of these segments, 14 (26%) showed enhanced tetrofosmin uptake after nitrate administration (≥10% vs baseline) and the remaining 38 (74%) did not change. The sensitivity and specificity of baseline tetrofosmin SPECT for detecting preserved metabolic activity were 69% and 86%, respectively. After nitrate administration, the sensitivity was higher (81%, P < .05 vs baseline) whereas the specificity was not different (86%, P = not significant). Concordance between tetrofosmin SPECT and PET in differentiating viable and necrotic myocardium was observed in 94 (72%) of the 131 akinetic or dyskinetic segments at baseline (k = 0.35) and in 108 segments (82%) after nitrate administration (k = 0.53).Conclusions. After nitrate administration, tetrofosmin uptake in dysfunctional segments correlated with metabolic activity as assessed by fluorodeoxyglucose PET imaging better than baseline. Thus tetrofosmin SPECT after nitrate administration may improve the identification of ischemic but still viable myocardium in patients with chronic ischemic LV dysfunction. (J Nucl Cardiol 2003;10:599-606.)

Bone mineral density in a population of children and adolescents with cerebral palsy and mental retardation with or without epilepsy

Purpose:  The present study aimed to assess bone mineral density (BMD) in a population of children and adolescents with cerebral palsy and mental retardation with or without epilepsy.