Francesco Scopinaro

Technetium-99m sestamibi: an indicator of breast cancer invasiveness

As recently shown, angiogenesis is the most reliable marker of breast cancer invasiveness. Unfortunately it must be assessed by immunohistochemistry on tissue specimens. We have used technetium-99m sestamibi, a marker of regional blood flow in other organs that often but not always images breast cancer, to assess the invasiveness of this tumour. Nineteen patients, ten with nodal metastases and nine without any metastases, were studied with 99mTc-sestamibi scintigraphy before operation. Angiogenesis was quantitatively assessed by immunohistochemical staining of endothelia for factor VIII. All the node-positive (N+) patients at surgical revision showed a positive 99mTc-sestamibi scan of the primary tumour and all the N-patients were negative. Nine out of ten N+ and sestamibi-positive tumours showed more than 135 microvessels/mm2 and one showed 99 microvessels/mm2; by contrast there were 71.6±12.1 microvessels/mm2 in the nine N- and sestamibi-negative tumours. Our study suggests that 99mTc-sestamibi is a marker of breast cancer invasiveness: its uptake is related to angiogenesis and, possibly, to oxidative metabolism of the tumour.

High-resolution scintimammography improves the accuracy of technetium-99m methoxyisobutylisonitrile scintimammography: use of a new dedicated gamma camera

Abstract. The main disadvantage of technetium-99m methoxyisobutylisonitrile (MIBI) prone scintimammography is its limited sensitivity for T1a and T1b cancers with a size of less than 1 cm. We have developed a high-resolution scintimammographic technique using a gamma camera based on a new concept, namely a position-sensitive photo-multiplier tube. The field of view of this camera, previously known as the SPEM (single photon emission mammography) camera, was 10 cm diameter. Scintimammographic images were acquired in the axial view; each breast was compressed to a thickness of 3–6 cm, modal class 4 cm. When the compressed breast was larger than the field of view, more than one study was performed in order to image the entire gland. Fifty-three patients were studied with high-resolution-scintimammography (HRSM) and Anger camera prone scintimammography (ACPSM). HRSM was performed 70 min after i.v. administration of 740 Mbq of 99mTc-MIBI; ACPSM images were acquired 10 and 60 min following the injection. Early 10-min ACPSM images were only evaluated for routine diagnostic purposes, while comparison was carried out between the 60-min ACPSM and 70-min HRSM images. At fine-needle aspiration (FNA) and/or open biopsy, 31 patients showed cancer: 15 T1c, 11 T1b and 5 T1a. In T1a-T1b cancers, the sensitivity of scintimammography was 50% with ACPSM and 81.2% with HRSM (P<0.01). Specificity was 86% with both techniques. HRSM is a promising new technique that improves the sensitivity of 99mTc-MIBI scintimammography in tumours sized less than 1 cm without apparently reducing its specificity. We are now working on a larger field-of-view camera.

Functional and ultrastructural evidence of myocardial stunning after acute carbon monoxide poisoning

OBJECTIVE To study human myocardial ultrastructural changes after carbon monoxide (CO) poisoning inducing reversible cardiac failure. DESIGN CASE REPORT clinical, functional and morphologic findings. SETTINGS Public university-affiliated hospital and electron microscopy laboratory. PATIENT A 25-yr-old woman with functional evidence of cardiac failure after acute CO poisoning. INTERVENTIONS Hyperbaric and intensive care treatment over 10 days. Scintigraphic and cardiac angiography with endomyocardial biopsy. MEASUREMENTS AND MAIN RESULTS Scintigraphy with 99mTc hexakis 2-methoxy-2-isobutyl isonitrile (sestaMIBI) showed an uptake defect in the left anterior descending artery territory. The cardiac angiography demonstrated a slight hypokinesis of the superior two thirds of the anterior wall and of the septal region with completely normal coronary angiograms. Electron microscopy of left ventricular biopsies showed slight ultrastructural changes in the myocytes. In addition, large glycogen deposits were mostly associated with swollen mitochondria. The patient was discharged in good clinical condition on day 10. CONCLUSIONS Presence of glycogen deposits associated with abnormal mitochondria may be signs of the incapability of myocardial cells in utilizing energy substrata. In the presence of normal myocardial perfusion, our findings are consistent with the presence of a stunned myocardium-like syndrome. Early recognition and treatment of this clinical syndrome allow the prevention of myocardial infarction.

Use of the somatostatin analogue octreotide to localise and manage somatostatin-producing tumours

Background—Somatostatin receptor scintigraphy (SRS) and octreotide therapy have both changed the management of gastroenteropancreatic endocrine tumours, but very few data are available on the use of SRS and octreotide to visualise and treat somatostatinomas. Method—The results of SRS and octreotide treatment in three somatostatinoma patients were examined. Results—SRS was able to detect extensive hepatic involvement in patient 1, one hepatic and one pancreatic lesion in patient 2, and one hepatic lesion in patient 3. Octreotide therapy (0.5 mg/day subcutaneously) was effective in decreasing plasma levels of somatostatin in all three patients. Symptoms (diabetes and diarrhoea) were greatly improved in the two patients with “somatostatinoma syndrome”. Conclusion—The study shows that somatostatinoma, like most other gastroenteropancreatic endocrine tumours, possesses functioning somatostatin receptors.

90Y PET-based dosimetry after selective internal radiotherapy treatments

Objectives The decay of 90Y has a minor branch to the O+ first excited state of 89Zr, the de-excitation of which to the fundamental state is followed by a &bgr;+–&bgr;− emission that has been used recently for biodistribution assessment after selective internal radiotherapy (SIRT) treatments. The purpose of the present study is to demonstrate the feasibility of 90Y PET imaging for dose assessment after radioembolization with 90Y microspheres. Methods Activity quantification was validated through preliminary phantom studies using a cylindrical body phantom composed of six inserts of different volumes filled with a calibrated amount of 90Y microspheres. A GE Discovery ST PET/CT scanner provided with bismuth germinate (BGO) crystals was used for image acquisition. Images were reconstructed with an ordered subset expectation–maximization method. The effect of object size and the effect of the number of iterations on dose evaluation and volume recovery were investigated. Microsphere dose distribution was then evaluated on one patient (one lesion) who underwent liver SIRT treatment. Dose calculations were made with a MATLAB-based code developed in our department. Dedicated Monte Carlo calculations were executed to evaluate dose S-values for the 90Y source. The activity distribution derived from 90Y PET acquisitions was convolved with the voxel S-values to obtain a three-dimensional absorbed dose distribution and dose–volume histograms. Results Dosimetry studies carried out on the body phantom with ordered subset expectation–maximization algorithm, three iterations, provided an accuracy of 7.62% in determining the absorbed dose in the largest insert. The dose difference increases as the insert size reduces. Preliminary results on a patient provided a high-resolution absorbed dose distribution map. An average dose of 139.3 Gy was evaluated for the tumor area, with a maximum dose as high as 237.9 Gy. The absorbed dose to the healthy liver was below the tolerance dose of 35 Gy (33.8 Gy). A clear correlation between absorbed dose and tumor response was observed at 18F-fluorodeoxyglucose PET acquired 6 months after treatment. Conclusion According to our experience, 90Y PET is a promising and reliable technique for microsphere dose assessment and might pave the way for a patient-specific PET-based dosimetry after liver SIRT treatments.

99mTc-interleukin-2 scintigraphy for the in vivo imaging of vulnerable atherosclerotic plaques

PurposeSeveral histopathological studies have demonstrated that vulnerable plaques are enriched in inflammatory cells. The aims of this study were: (1a) to test the ability of 99mTc-labelled interleukin-2 (99mTc-IL2) to bind to IL2R-positive (IL2R+) cells in carotid plaques and (1b) to correlate the plaque uptake of 99mTc-IL2, measured in vivo, with the number of IL2R+ cells within the plaque, measured ex vivo by histology (transversal study, TS), and (2) to evaluate changes in 99mTc-IL2 uptake in plaques, before and after treatment with a statin or a hypocholesterolaemic diet (longitudinal study, LS).MethodsUltrasound scan was performed for plaque characterisation and localisation. Fourteen patients (16 plaques) eligible for endoarterectomy were recruited for the TS and underwent 99mTc-IL2 scintigraphy before surgery. Nine patients (13 plaques) were recruited for the LS; these patients received atorvastatin or a standard hypocholesterolaemic diet and 99mTc-IL2 scintigraphy was performed before and after 3 months of treatment.ResultsThe degree of 99mTc-IL2 uptake was expressed as the plaque/background (T/B) ratio. In patients from TS, T/B ratios correlated with the percentage of IL2R+ cells at histology (r=0.707; p=0.002) and the number of IL2R+ cells at flow cytometry (r=0.711; p=0.006). No correlations were observed between ultrasound scores and either scintigraphic or histological findings. In patients from the LS, the mean 99mTc-IL2 uptake decreased in statin-treated patients (1.75±0.50 vs 2.16±0.44; p=0.012), while it was unchanged in the patients on the hypocholesterolaemic diet (2.33±0.45 vs 2.34±0.5).Conclusion99mTc-IL2 accumulates in vulnerable carotid plaques; this accumulation is correlated with the amount of IL2R+ cells and is influenced by lipid-lowering treatment with a statin.

Outcome of endoscopic sphincterotomy in post cholecystectomy patients with sphincter of Oddi dysfunction as predicted by manometry and quantitative choledochoscintigraphy

Background: Sphincter of Oddi dysfunction is diagnosed at manometry and, after cholecystectomy, non-invasively at quantitative choledochoscintigraphy. Patients may benefit from endoscopic sphincterotomy. Aims: The aim of this study was to assess the usefulness of choledochoscintigraphy compared with manometry in predicting outcome of sphincterotomy in post cholecystectomy patients with sphincter of Oddi dysfunction. Patients and methods: Thirty patients with biliary-type pain complying with the Rome diagnostic criteria of sphincter of Oddi dysfunction and belonging to biliary group I and II were subjected to clinical evaluation, choledochoscintigraphic assessment of the hepatic hilum-duodenum transit time, endoscopic retrograde cholangiopancreatography, and perendoscopic manometry. Twenty two biliary group I and II patients with prolonged hepatic hilum-duodenum transit times were invited to undergo sphincterotomy. Fourteen patients underwent sphincterotomy; eight refused. Clinical and scintigraphic assessments were performed at follow up. Results: Hepatic hilum-duodenum transit time was delayed in all patients with manometric evidence of sphincter of Oddi dysfunction, in all biliary group I patients and in 64% of biliary group II patients. At follow up, all patients who underwent sphincterotomy were symptom free and hepatic hilum-duodenum transit time had either normalised or significantly improved. A favourable post sphincterotomy outcome was predicted in 93% of cases at choledochoscintigraphy and in 57% at manometry. Conclusions: Quantitative choledochoscintigraphy is a useful and non-invasive test to diagnose sphincter of Oddi dysfunction as well as a reliable predictor of sphincterotomy outcome in post cholecystectomy biliary group I and II patients, irrespective of clinical classification and manometric findings.

Accuracy and safety of technetium-99m hexakis 2-methoxy-2-isobutyl isonitrile (Sestamibi) myocardial scintigraphy with high dose dipyridamole test in patients with effort angina pectoris: A multicenter study

Clinical and physiologic evidence indicates that maximal coronary vasodilation is not achieved in a large number of patients with use of the standard dose of dipyridamole (0.56 mg/kg body weight over 4 min). The feasibility, safety and accuracy of technetium-99m hexakis 2-methoxy-2-isobutyl isonitrile (Sestamibi) scintigraphy associated with intravenous high dose dipyridamole (0.56 mg/kg over 4 min followed 4 min later by an additional 0.28 mg/kg over 2 min) were evaluated in a multicenter study. Planar myocardial perfusion images were obtained at rest and after dipyridamole in 101 patients with effort chest pain and no prior myocardial infarction. High dose dipyridamole (62 patients) was used when typical chest pain or electrocardiographic (ECG) signs of ischemia, or both, did not occur during or after the standard dose (39 patients). With high dose dipyridamole, 34 patients had pain (18 patients) or ECG signs of ischemia (ST depression greater than or equal to 2 mm) (8 patients), or both (8 patients), whereas the other 28 patients had Sestamibi injection in the absence of symptoms or ECG changes. All patients underwent coronary angiography: 81 had significant coronary artery disease (greater than or equal to 50% reduction of lumen diameter) (affecting one vessel in 38, two vessels in 19 and three vessels in 24 patients) and 20 patients had normal coronary arteries. The overall sensitivity, specificity and predictive accuracy of Sestamibi scintigraphy were 81%, 90% and 83%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

HEPATODUODENAL BILE TRANSIT IN CHOLECYSTECTOMIZED SUBJECTS : RELATIONSHIP WITH SPHINCTER OF ODDI FUNCTION AND DIAGNOSTIC VALUE

The hepatic hilum-duodenum transit time (HHDT) was evaluated in cholecystectomized subjects to assess its relationship with the motor function of the sphincter of Oddi (SO) and its diagnostic accuracy in the detection of SO dysfunction. The study was performed in asymptomatic controls and symptomatic patients with SO dysfunction before and after sphincterotomy. HHDT showed a direct correlation with manometric SO maximal basal pressure (r=0.77;P<0.001) but not with SO phasic activity. In sphincterotomized subjects HHDT did not differ from that of the asymptomatic subjects, and HHDT, which was prolonged before sphincterotomy, normalized after sphincterotomy. HHDT had a 100% specificity and an 83% sensitivity in diagnosing SO dysfunction when compared to SO manometry. In conclusion, the cholescintigraphic HHDT is mainly related to the SO maximal basal pressure, presenting an elevated specificity and a satisfactory sensitivity in the diagnosis of SO dysfunction in cholecystectomized subjects.

SCINTILLATING ARRAY GAMMA CAMERA FOR CLINICAL USE

Abstract Dedicated gamma cameras for specific clinical application are representing a new trend in Nuclear Medicine. They are based on Position Sensitive Photo Multiplier Tubes (PSPMT). The main intrinsic limitation of large area PSPMT (5″ diameter) is the photocathode glass window. Coupling to a planar scintillation crystal strongly affects the useful active area and the intrinsic spatial resolution. To overcome this limitation at University of Rome “La Sapienza” was developed the first 5″ diameter gamma camera consisting of a Hamamatsu R3292 PSPMT coupled to 50 × 50 YAP: Ce scintillating array. The array pixel size is 2 × 2 mm2 and the overall dimension of multi-crystal is 10 × 10 × 1 cm3. Resistive chains were used to calculate the centroid. The scintillating array produces a focused light spot minimising the spread introduced by PSPMT glass window. The intrinsic spatial resolution varied between 2 and 2.7 mm. The position linearity and useful active area resulted in good agreement with intrinsic one obtained by light spot irradiation. The real limitation was the poor energy resolution of an individual crystal (40%) and the poor uniformity response of PSPMT (within ±15%). A correction matrix was then carried out by which a 57% of total energy resolution was obtained for the whole matrix. The camera is currently operating as Single Photon Emission Mammography (SPEM) and it is producing breast functional images for malignant tumour detection using the same geometry as standard X-ray mammography.