Orazio Schillaci

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.

Hybrid SPECT/CT: a new era for SPECT imaging?

In recent years the use of medical images in healthcare has grown considerably, mainly due to the rapid evolution of imaging techniques. Now, it is usual for patients to be imaged several times, and a great number of imaging studies are generated. For physicians, it is essential to relate one image to another before rendering an interpretation. Medical images allow the assessment of both the anatomical condition and the functional status of the patient; fusion imaging combines morphological studies with functional ones, thereby overcoming the drawbacks of both modalities and emphasising their individual strengths. In many clinical scenarios, images from different studies are compared by visual analysis, with the observer mentally synthesising the various findings. This intellectual process is very important, but it has been greatly facilitated by the recent development of dual-modality integrated imaging systems (SPECT/CT and PET/CT), which provide functional and anatomical images in the same scanning session, with the acquired images co-registered by means of the hardware [1]. While integrated SPECT/CT applications are not yet so important as those of PET/CT, the first published studies have demonstrated that SPECT/CT can be very useful, because it is able to provide further information of clinical value in several circumstances, and especially in the imaging of tumours. In fact, despite the growing applications of PETand PET/CT in oncology, there is still much that can be done using single-photon emitting radiopharmaceuticals. Currently, more potent SPECT/CT systems are being introduced, incorporating state-of-the-art SPECT with multi-slice CT (up to 16 slices), which allows the acquisition of diagnostic CT images. Until recently, however, only one commercial system with SPECT/CT capability has been available. This hybrid imaging device combines a dual-detector, variable angle gamma camera with a lowdose X-ray tube, attached to the same gantry. This system enables, in a sequential interchangeable sequence, the acquisition, together with SPECT data, of cross-sectional X-ray transmission images, which accurately locate the anatomical sites of radiotracer uptake. The CT data can also be used for attenuation and scatter correction of the emission images [2]. After acquisition, matching emission and transmission data are quickly fused, generating images of SPECT data superimposed on the corresponding anatomical planes. The main drawback of the above-described hybrid device is its low-dose CT scan, which provides low-resolution images that are useful for spatial localisation and fusion with SPECT data but cannot substitute for high-resolution diagnostic CT. Nevertheless, this system is able to provide adequate information for the precise assessment of SPECT findings in most studies. In those cases with insufficient information to permit localisation of a site of radiopharmaceutical uptake, the low-resolution CT images are still useful to define more precisely the appropriate slices to review from a diagnostic quality CT or MR scan, i.e. those slices that match up with the area of interest. Moreover, it is worth noting that the radiation burden due to CT in this device is only about 0.5 mSv, because the X-ray tube operates at 2.5 mA [3]; this aspect is particularly important when a patient has formerly been submitted to a diagnostic CT scan, and it should be taken into due account. When we started working with our SPECT/CT system in 2001, the first question we asked ourselves was whether this hybrid device could be really useful in improving SPECT interpretation. Therefore, to investigate the additional value of SPECT/CT imaging compared with SPECT alone, we began to analyse SPECT images in isolation and then re-evaluated them with the addition of fused images. Based on the results of the first studies performed, we concluded that this new technology can be routinely employed, facilitating the interpretation of SPECT imaging. In fact, in a series of 81 consecutive patients evaluated for various clinical situations, using different radiopharmaceuticals, SPECT/CT improved upon SPECT analysis alone in 41% of cases: it provided correct localisation of SPECT findings in 23 patients, allowed the exclusion of disease at sites of physiological radiotracer uptake in eight cases and defined the functional significance of CT lesions in two patients [4]. These preliminary findings were in accordance with the results of the first clinical paper published on the use of SPECT/CT, which reported a similar improvement in Editorial

18F-choline PET/CT physiological distribution and pitfalls in image interpretation: experience in 80 patients with prostate cancer.

Objectives18F-choline positron emission tomography (PET)/computed tomography (CT) is an integral part in restaging of patients with prostate cancer (PC). The aim of this study was to describe the whole-body physiologic distribution of 18F-choline and to discuss some abnormal sites of uptake not related to PC we observed. Materials and methodsEighty consecutive patients submitted to 18F-choline PET/CT imaging for primary staging or biochemical recurrence (prostate specific antigen rising) after treatment of PC was considered. Whole-body PET/CT was acquired approximately 40 min after 18F-choline injection. ResultsWe observed physiological 18F-choline uptake in liver, pancreas, spleen, salivary and lachrymal glands and also, owing to renal excretion, in urinary tract. Other sites of less intense tracer uptake were bone marrow and intestines. We found abnormal and unexpected PET findings in 15 patients (18.7%), not owing to PC localizations. The majority of these findings were owing to inflammation (12 of 15); a case of low grade lymphoma was detected; two patients showed focal brain uptake of 18F-choline and were subsequently submitted to magnetic resonance: in one a meningioma and in the other a low-grade brain tumour were diagnosed. ConclusionAccurate knowledge of the biodistribution of 18F-choline is essential for the correct interpretation of PET/CT imaging. CT enables differentiation of physiological bowel activity and 18F-choline excretion in the ureters. In our series, 18F-choline uptake in benign pathological conditions mainly included sites of inflammation; nevertheless, accumulation in tumour deposits not because PC cannot be excluded, particularly in the brain, where correlative imaging with magnetic resonance is of the utmost importance.

Sentinel node in breast cancer procedural guidelines.

ContentProcedure guidelines for scintigraphic detection of sentinel node in breast cancer are presented.AuthorsThe paper was written by several experts in this field on behalf of the European Association of Nuclear Medicine Oncology and Dosimetry committees and approved by the Executive Committee.

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.

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.

123I-FP-CIT semi-quantitative SPECT detects preclinical bilateral dopaminergic deficit in early Parkinson's disease with unilateral symptoms.

Background and aim123I-FP-CIT SPECT has been successfully used to detect the loss of dopaminergic nigrostriatal neurons in Parkinsons disease at an early stage. In this study we evaluated the capacity of 123I-FP-CIT SPECT to assess bilateral dopamine transporter (DAT) loss in de-novo hemi-Parkinsons disease (PD) patients with one-sided clinical symptoms. Patients and methodsTwenty-nine de-novo hemi-PD patients at an early stage (Hoehn & Yahr stage 1) and 18 gender and age matched healthy subjects were studied. SPECT imaging was always performed at 4 h post-injection. The ratios of striatal (S) to non-specific occipital (O) binding for the entire striatum (S/O), caudate nuclei (C/O), putamina (Pput/O), and the putamen to caudate nucleus index (Pput/C) were calculated in both the basal ganglia. ResultsIn PD patients S/O, C/O and Pput/O ratio values contralateral to the clinically affected side were significantly lower (P<0.001) than in the control group (−38%, −34% and −42%, respectively). A significant reduction (P<0.001) of the striatal binding ratios was also found ipsilaterally (S/O, −31%; C/O, −28%; Pput/O, −33%). The Pput/C index was also bilaterally significantly reduced (P<0.01). DAT loss was significantly greater (P<0.001) in the contralateral than in the ipsilateral S; and putamen bilaterally presented a higher dopaminergic deficit than did caudate. ConclusionOur results indicate that semi-quantitative 123I-FP-CIT SPECT detects a bilateral dopaminergic deficit in early PD with unilateral symptoms and preclinical DAT loss in the ipsilateral striatal binding, corresponding to the side not yet affected by motor signs. Semi-quantitative analysis may thus be used to diagnose PD at an early stage as well as to identify individuals developing bilateral dopaminergic damage.

Diabetic Foot Infection: Usefulness of SPECT/CT for 99mTc-HMPAO-Labeled Leukocyte Imaging

Our aim was to evaluate the role of SPECT/CT for the diagnosis of diabetic foot infection by labeled leukocytes. Methods: Seventeen patients with 19 clinically suspected sites of infection were included. After leukocyte labeling and administration, planar scans were acquired at 30 min, 4 h, and 24 h for 18 consecutive patients. SPECT/CT was obtained at 6 h. The final diagnosis was established by clinical follow-up (24 mo) in all cases and by bone biopsy for 14 sites. Results: Leukocyte scanning was positive in 16 of 19 lesions and negative in 3. SPECT/CT changed the interpretation of the planar and SPECT images for 10 of 19 suspected sites (52.6%): it excluded osteomyelitis in 6 cases, revealed bone infection in 1 case, and revealed both bone and soft-tissue infection in 3 cases. The hybrid device did not significantly contribute to the evaluation of patients with negative scan results. Conclusion: SPECT/CT can be useful for a more accurate diagnosis of diabetic foot infection by labeled leukocyte imaging.

18F-choline PET/CT pitfalls in image interpretation: An update on 300 examined patients with prostate cancer

Objectives 18F-choline PET/CT is an important diagnostic tool in the management of patients with prostate cancer (PC). The aim of this study was to describe and discuss some abnormal sites of uptake that we observed, not due to PC recurrence. Patients and Methods Three hundred patients were submitted to 18F-choline PET/CT for staging or restaging of PC. Whole-body PET/CT was acquired 40 minutes after the 18F-choline administration. Results We found abnormal uptake of the tracer, not related to PC, in 48/300 patients (16%). Most of these findings were due to inflammatory processes. Furthermore, some malignant conditions, such as a case of colon cancer, a case of bladder carcinoma, and a multiple myeloma, were diagnosed. Mild uptake was also detected in some benign diseases, such as thymoma, adrenal adenoma, and sarcoidosis. Six patients showed focal brain uptake in correspondence to a meningioma. Conclusions It is necessary for nuclear physicians, during clinical practice, to consider the possibility of 18F-choline uptake in some benign or malignant conditions for the intrinsic pharmacologic property of the tracer. An accurate medical investigation, correlative imaging with CT and/or MRI with contrast agents, laboratory data, and above all, histologic examination are often necessary for correct diagnosis.