Marco Spadafora

Effect of trimetazidine on 99Tcm-tetrofosmin uptake in patients with coronary artery disease.

Myocardial uptake of 99Tcm-tetrofosmin in vivo is determined by a combination of flow and metabolic status of myocytes. The accumulation of tetrofosmin in the mitochondria is related to their ability to transduce metabolic energy into electronegative membrane potential. Trimetazidine (TMZ), an anti-ischaemic drug, appears to have a metabolic cytoprotective effect related to mitochondrial function, since it does not induce systemic or coronary haemodynamic changes. In this study, we evaluated the effects of TMZ on tetrofosmin uptake in hypoperfused myocardial regions in patients with coronary artery disease (CAD). Twenty-two patients, 14 with previous myocardial infarction (group A) and eight with a history of angina (group B), with angiographically documented CAD were studied. All patients underwent two tetrofosmin SPET studies at rest, before (baseline) and 1 week after TMZ administration (post-TMZ). On quantitative analysis, 131 segments showed less tetrofosmin uptake at baseline. In these segments, tetrofosmin uptake was 51±13% at baseline and 55±15% post-TMZ (P<0.001 vs control). In the 86 hypoperfused segments of group A, tetrofosmin uptake was 48±14% at baseline and 52±17% post-TMZ (P<0.001 vs control). In the 45 hypoperfused segments of group B, tetrofosmin uptake was 56±9% at baseline and 60±10% post-TMZ (P<0.001 vs control). In the remaining 309 segments, no significant difference in tetrofosmin uptake before and after TMZ was observed. In conclusion, our results suggest that TMZ administration may increase myocardial uptake of tetrofosmin in hypoperfused regions at rest in patients with CAD, based on its metabolic effect.

Addition of atropine to submaximal exercise stress testing in patients evaluated for suspected ischaemia with SPECT imaging: a randomized, placebo-controlled trial

PurposeTo evaluate the effects of the addition of atropine to exercise testing in patients who failed to achieve their target heart rate (HR) during stress myocardial perfusion imaging with single-photon emission computed tomography (SPECT).MethodsThe study was a prospective, randomized, placebo-controlled design. Patients with suspected or known coronary artery disease who failed to achieve a target HR (≥85% of maximal predicted HR) during exercise SPECT imaging were randomized to receive intravenous atropine (n = 100) or placebo (n = 101).ResultsThe two groups of patients did not differ with respect to demographic or clinical characteristics. A higher proportion of patients in the atropine group achieved the target HR compared to the placebo group (60% versus 3%, p < 0.0001). SPECT imaging was abnormal in a higher proportion of patients in the atropine group as compared to the placebo group (57% versus 42%, p < 0.05). Stress-induced myocardial ischaemia was present in more patients in the atropine group as compared to placebo (47% versus 29%, p < 0.01). In both groups of patients, no major side effects occurred.ConclusionThe addition of atropine at the end of exercise testing is more effective than placebo in raising HR to adequate levels, without additional risks of complications. The use of atropine in patients who initially failed to achieve their maximal predicted HR is associated with a higher probability of achieving a diagnostic myocardial perfusion study.

Segmental 18F-FDG-PET/CT in a single pulmonary nodule: a better cost/effectiveness strategy

A solitary pulmonary nodule (SPN) is one of the most frequent computed tomography (CT) incidental findings. Its characterization is of paramount relevance, since prognosis of malignant pulmonary lesions is strictly related to a tumor’s dimension at diagnosis [1, 2]. Actually, although lung cancer is the leading cause of cancer death worldwide, a favorable 5-year survival rate up to 80 % [3] after surgical resection at an earlier stage, has been observed. Thus, it appears mandatory to define appropriate diagnostic strategies for an early characterization of SPN, and diagnostic imaging plays a major role in this process. In recent years there have been serious concerns about both the rapid increase of cancer risk associated with medical exposure to ionizing radiation, about six fold over a 25-year period [4], and health care costs, particularly for those associated with advanced imaging techniques [5]. These elements, together with the diagnostic accuracy, are fundamental in defining cost-effectiveness of an imaging modality. Although Ffluorodeoxiglucose (FDG) Positron Emission Tomography – Computed Tomography (PET/CT) is integrated into the SPN clinical guidelines [6–8], a different PET/CTcost/effective strategy could affect its position, with a wider and more effective application in clinical flow charts through a cost and dosimetric impact reduction and a better diagnostic accuracy. Diagnostic imaging in SPN

Italian Tailored Assessment of Lung Indeterminate Accidental Nodule by Proposing a Segmental Pet/Computed Tomography (S-Pet/Ct): Rationale And Study Design of a Retrospective, Multicenter Trial

BACKGROUND The Italian Tailored Assessment of Lung Indeterminate Accidental Nodule (ITALIAN) is a retrospective, multicenter trial designed to compare the diagnostic information provided by segmental positron emission tomography (PET)/computed tomography (CT) (s-PET/CT) with those of whole body (wb)-PET/CT in patients with single pulmonary nodules (SPN). This report describes the details and implications of the ITALIAN trial design. METHODS AND RESULTS Between September 2016 and May 2017, 502 consecutive patients (302 men, mean age 67±12 years) with SPN undergoing 18F-fluorodeoxyglucose (FDG) PET/CT were enrolled. PET/CT images will be visually and semiquantitatively evaluated. For visual analysis, a 4-point scoring system (1=absent; 2=mild; 3=moderate and 4=intense) will be used; for semiquantitative analysis, maximum standardized uptake value (SUV) in the SPN and mean SUV in the mediastinal blood pool and in the liver will be computed. CONCLUSION The results of this trial might help to define the role of s-PET/CT in patients with SPN. This trial will also evaluate the impact on radiobiology and costs subsequent the introduction of this alternative imaging acquisition modality.

Alternative imaging strategy of solitary pulmonary nodule by FDG PET/CT: Can be imagined a tailored PET?

OBJECTIVE Patients with solitary pulmonary nodule (SPN) are usually sent to total-body positron emission tomography/computed tomography (PET/CT) examination with 18F-fluorodeoxyglucose (FDG). However, a segmental scan strategy may improve cost/effectiveness in this category of patients. CONCLUSION A segmental PET/CT scan only at the chest level could be performed in patients with indeterminate SPN. Limiting the PET/CT field to the thoracic region would greatly affect on radiobiology, department organization and health-care costs.

The delicate balance between present and future.

Dear Sir, We thank Roland Hustinx [1] for his criticisms of our paper [2], supporting the possibility to avoid a whole-body PET/CT (wb-PET/CT) scan in selected patients with solitary pulmonary nodules (SPN). Hustinx analyzes with clarity and rigor the contraindications and difficulties that may arise on the road from this proposal to its routine implementation. However, while we agree that wb-PET/CT is mandatory in patients with diagnosed T1 lung cancer, we believe that a segmental approach could bemore appropriate in a large number of subjects undergoing to PET/CT to evaluate SPN. Actually, on the basis of clinical guidelines [3, 4] recommending PET/CT to characterize the nodule and according to the ALARA principle, a segmental approach could be suggested in a broad spectrum of intermediate risk patients, from 5 to 10% and up to 65%. The issue of ionizing radiation is delicate, and must be addressed in a balanced way. On the basis of a Biological Effects of Ionizing Radiation VII Phase 2 report [5], the reduction of 6 mSv associated with a segmental approach may avoid one cancer in every 4000 exams in a 60year-old male, and one cancer in every 2466 exams in a 50year-old woman. Also figuring that this estimate occupies the most alarmist side of the spectrum of positions, it is otherwise unlikely that, on the contrary, this significant reduction of radiation should be considered a negligible objective. We also agree with Hustinx that a segmental PET strategy transferred into the current reality may create some organizational and logistical problems. Nevertheless, these aspects may become less relevant in the case the number of segmental studies that have to be further completed with a WB scan will result quite low [6]. Moreover, some procedural critical points are such only if you plan to drop a new approach in the present organizational workflow, without assuming new scenarios and organizational changes that can facilitate its implementation. Although PET/CT is an important tool in metabolic and molecular characterization, it still suffers from reduced flexibility, with negative effects on its larger application. The present diagnostic philosophy requires that the patient has to fit the strict procedural rules of PET/ CT, while we retain that the patient has to be considered the center of the PET/CT universe. We strongly believe that efforts should be made in this direction, confident that a Bsegmental philosophy^ can determine further development of PET indications.

Stress protocol and accuracy of myocardial perfusion imaging: Is it better to start from the end?

The strength of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is mainly due to the prognostic value also related with the choice of optimal therapeutic strategy. In the current era of comparative effectiveness and outcomes research, we are seeing a progressive shift from a diagnostic approach to a riskand care costs-management of coronary artery disease (CAD). Recent technological advances in SPECT hardware and software, new stressors, and clinical protocols have improved the clinical impact and cost effectiveness of MPI. Particularly, the novel cadmium zinc telluride (CZT) SPECT cameras provide fast high-quality MPI and seem to allow for a more accurate evaluation of myocardial ischemia with lower administered doses. In this issue of the Journal, Gimelli et al assessed with a CZT camera the diagnostic accuracy of MPI for both pharmacologic and exercise stress test, also in patients undergoing sub-maximal exercise. They found an elevated accuracy of MPI, independently on both stress protocol and level of exercise stress testing. The topic is important, and the possibility that enhanced accuracy by CZT cameras could help to partially overcome the limitations of exercise level threshold, usually expressed as 85% of age-predicted maximal heart rate (HR), is of clinical relevance, expanding the indication of exercise test over pharmacologic stressor. However, there are some issues that should be taken into account. THE CONCEPT ‘‘START FROM THE END’’

Risk-related 18F-FDG PET/CT and new diagnostic strategies in patients with solitary pulmonary nodule: the ITALIAN multicenter trial

PurposeDiagnosis of solitary pulmonary nodule (SPN) is an important public health issue and 18F-FDG PET/CT has proven to be more effective than CT alone. Pre-test risk stratification and clinical presentation of SPN could affect the diagnostic strategy. A relevant issue is whether thoracic segmental (s)-PET/CT could be implemented in patients with SPN. This retrospective multicenter study compared the results of FDG whole-body (wb)-PET/CT to those of s-PET/CT.Methods18F-FDG PET/CT of 502 patients, stratified for pre-test cancer risk, were retrospectively analyzed. The thoracic part of wb-PET/CT, considered s-PET/CT, was compared to wb-PET/CT. Clinical and PET/CT variables were investigated for SPN characterization as well as for identification of patients in whom s-PET/CT could be performed. Histopathology or follow-up data were used as a reference.ResultsIn the study population, 36% had malignant, 35% benign, and 29% indeterminate SPN. 18F-FDG uptake indicative of thoracic and extra-thoracic lesions was detectable in 13% and 3% of the patients. All patients with extra-thoracic metastases (n = 13) had thoracic lymph node involvement and highest 18F-FDG uptake at level of SPN (negative predictive value 100%). Compared to wb-PET/CT, s-PET/CT could save about 2/3 of 18F-FDG dose, radiation exposure or scan-time, without affecting the clinical impact of PET/CT.ConclusionPre-test probability of malignancy can guide the diagnostic strategy of 18FDG-PET/CT in patients with SPN. In subjects with low-intermediate pretest probability s-PET/CT imaging might be planned in advance, while in those at high risk and with thoracic lymph node involvement a wb-PET/CT is necessary.