Cristina Nanni

Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation

We prospectively analyzed the prognostic relevance of positron emission tomography-computed tomography (PET/CT) at diagnosis, after thalidomide-dexamethasone (TD) induction therapy and double autotransplantation (ASCT) in 192 newly diagnosed multiple myeloma (MM) patients. Presence at baseline of at least 3 focal lesions (FLs; 44% of cases), a standardized uptake value (SUV) > 4.2 (46%), and extramedullary disease (EMD; 6%) adversely affected 4-year estimates of progression-free survival (PFS; ≥ 3 FLs: 50%; SUV > 4.2: 43%; presence of EMD: 28%). SUV > 4.2 and EMD were also correlated with shorter overall survival (OS; 4-year rates: 77% and 66%, respectively). Persistence of SUV > 4.2 after TD induction was an early predictor for shorter PFS. Three months after ASCT, PET/CT was negative in 65% of patients whose 4-year rates of PFS and OS were superior to those of PET-positive patients (PFS: 66% and OS: 89%). In a multivariate analysis, both EMD and SUV > 4.2 at baseline and persistence of fluorodeoxyglucose (FDG) uptake after ASCT were independent variables adversely affecting PFS. PET/CT involvement at diagnosis, after novel agent-based induction and subsequent ASCT is a reliable predictor of prognosis in MM patients. This study is registered at www.clinicaltrials.gov as NTC01341262.

Influence of Trigger PSA and PSA Kinetics on 11C-Choline PET/CT Detection Rate in Patients with Biochemical Relapse After Radical Prostatectomy

The purpose of this study was to investigate the effect of total prostate-specific antigen (PSA) at the time of 11C-choline PET/CT (trigger PSA), PSA velocity (PSAvel), and PSA doubling time (PSAdt) on 11C-choline PET/CT detection rate in patients treated with radical prostatectomy for prostate cancer, who showed biochemical failure during follow-up. Methods: A total of 190 patients treated with radical prostatectomy for prostate cancer who showed an increase in PSA (mean, 4.2; median, 2.1; range, 0.2–25.4 ng/mL) were retrospectively enrolled. All patients were studied with 11C-choline PET/CT. Patients were grouped according to trigger PSA (PSA ≤ 1 ng/mL, 1 < PSA ≤ 2 ng/mL, 2 < PSA ≤ 5 ng/mL, and PSA > 5 ng/mL). In 106 patients, data were available for calculation of PSAvel and PSAdt. Logistic regression analysis was used to determine whether there was a relationship between PSA levels and PSA kinetics and the rate of detection of relapse using PET. Results: 11C-choline PET/CT detected disease relapse in 74 of 190 patients (38.9%). The detection rate of 11C-choline PET/CT was 19%, 25%, 41%, and 67% in the 4 subgroups—PSA ≤ 1 ng/mL (51 patients), 1 < PSA ≤ 2 ng/mL (39 patients), 2 < PSA ≤ 5 ng/mL (51 patients), and PSA > 5 ng/mL (49 patients)—respectively. Trigger PSA values were statistically different between PET-positive patients (median PSA, 4.0 ng/mL) and PET-negative patients (median PSA, 1.4 ng/mL) (P = 0.0001). Receiver-operating-characteristic analysis showed an optimal cutoff point for trigger PSA of 2.43 ng/mL (area under the curve, 0.76). In 106 patients, PSAdt and PSAvel values were statistically different between patients with PET-positive and -negative scan findings (P = 0.04 and P = 0.03). The 11C-choline PET/CT detection rate was 12%, 34%, 42%, and 70%, respectively, in patients with PSAvel < 1 ng/mL/y (33 patients), 1 < PSAvel ≤ 2 ng/mL/y (26 patients), 2 < PSAvel ≤ 5 ng/mL/y (19 patients), and PSAvel > 5 ng/mL/y (28 patients). The 11C-choline PET/CT detection rate was 20%, 40%, 48%, and 60%, respectively, in patients with PSAdt > 6 mo (45 patients), 4 < PSAdt ≤ 6 mo (20 patients), 2 < PSAdt ≤ 4 mo (31 patients), and PSAdt ≤ 2 mo (10 patients). There was no statistical difference between PET-positive and -negative scan detection rates according to the Gleason score, pT and N status, patient age, or duration between surgery and biochemical relapse. Trigger PSA and PSAvel were found to be independent predictive factors for a PET-positive result (P = 0.002; P = 0.04) and PSAdt was found to be an independent factor only in patients with trigger PSA less than 2 ng/mL (P = 0.05) using multivariate analysis. Conclusion: The 11C-choline PET/CT detection rate is influenced by trigger PSA, PSAdt, and PSAvel. This finding could be used to improve the selection of patients for scanning by reducing the number of false-negative scans and increasing the detection rate of disease in patients with early relapse and potentially curative disease.

Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours

Purpose18F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that 18F-DOPA and 68Ga-DOTA-NOC are more accurate for disease assessment and 68Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET.AimThe aim of this study was to compare 68Ga-DOTA-NOC and 18F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours.Materials and methodsThirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for 18F-DOPA and 68Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging).ResultsThe most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. 68Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while 18F-DOPA PET was positive in 9/13. On a lesions basis, 68Ga-DOTA-NOC identified more lesions than 18F-DOPA (71 vs 45), especially at liver, lung and lymph node level. 68Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while 18F-DOPA identified the primary only in two of eight cases.ConclusionsAlthough the patients studied are few and heterogeneous, our data show that 68Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over 18F-DOPA.

68Ga-DOTANOC PET/CT clinical impact in patients with neuroendocrine tumors.

Several authors reported the superiority of 68Ga-DOTANOC PET/CT to conventional imaging (CI) for the assessment of neuroendocrine tumors (NET). However, the detection of a higher number of lesions is not necessarily followed by a modification of disease stage or therapeutic approach. The aim of this study was to assess the impact of 68Ga-DOTANOC PET/CT on the clinical management of NET patients. Methods: The study included 90 patients with pathologic confirmation of NET, CT performed within a month of 68Ga-DOTANOC PET/CT, and a follow-up period of at least 1 y. PET/CT results were compared with CI results. As a standard of reference to finally evaluate PET results, clinical and imaging follow-up data were used. To assess the clinical impact of PET findings, all referring physicians were contacted after PET and asked about how patients were managed. Stage or therapy modifications were independently recorded, and the overall impact was evaluated patient by patient if PET results either affected therapy or caused a change in disease stage. Results: Considering PET/CT and CI concordant cases (47/90 [52.2%]), PET findings affected the therapeutic management in 17 of 47 (36.2%) patients. Although PET did not result in modification of disease stage, 68Ga-DOTANOC detected a higher lesion number in most patients. PET/CT and CI findings were discordant in 42 of 90 (46.7%) patients: PET resulted in a modification of stage in 12 patients (28.6%) and affected the treatment plan in 32 patients (76.2%). PET and CT were both equivocal in 1 patient (1/90). Considering all cases, 68Ga-DOTANOC PET/CT affected either stage or therapy in 50 of 90 (55.5%) patients. The most frequent impact on management (27 patients) was the initiation or continuance of peptide receptor radionuclide therapy, followed by the initiation or continuance of somatostatin analog medical treatment (7 patients) and referral to surgery (6 patients). PET prevented unnecessary surgery in 6 patients and excluded from treatment with somatostatin analogs 2 patients with NET lesions that did not express somatostatin receptors. Less frequent impacts on management included the initiation of radiotherapy (1 patient), further diagnostic investigation (1 patient), and liver transplantation (1 patient). Conclusion: 68Ga-DOTANOC PET/CT either affected stage or caused a therapy modification in more than half the patients, thus confirming the clinical role of PET in the management of NET.

CB(1) signaling in forebrain and sympathetic neurons is a key determinant of endocannabinoid actions on energy balance.

The endocannabinoid system (ECS) plays a critical role in obesity development. The pharmacological blockade of cannabinoid receptor type 1 (CB(1)) has been shown to reduce body weight and to alleviate obesity-related metabolic disorders. An unsolved question is at which anatomical level CB(1) modulates energy balance and the mechanisms involved in its action. Here, we demonstrate that CB(1) receptors expressed in forebrain and sympathetic neurons play a key role in the pathophysiological development of diet-induced obesity. Conditional mutant mice lacking CB(1) expression in neurons known to control energy balance, but not in nonneuronal peripheral organs, displayed a lean phenotype and resistance to diet-induced obesity. This phenotype results from an increase in lipid oxidation and thermogenesis as a consequence of an enhanced sympathetic tone and a decrease in energy absorption. In conclusion, CB(1) signaling in the forebrain and sympathetic neurons is a key determinant of the ECS control of energy balance.

Preclinical In vivo Study of New Insulin-Like Growth Factor-I Receptor–Specific Inhibitor in Ewing's Sarcoma

Purpose: Small-molecule insulin-like growth factor-I receptor (IGF-IR)-specific tyrosine kinase inhibitors have been recently proposed as clinically viable approaches to impair IGF-IR functions. NVP-AEW541 seems one of the most promising agents. In this article, we point out its effects against migration, metastasis, vasculogenicity, and angiogenesis of Ewings sarcoma cells. Experimental Design:In vivo NVP-AEW541 effectiveness was analyzed against TC-71 Ewings sarcoma growth and bone metastasis after cell inoculation in athymic mice. Activity of the compound against angiogenesis as well as vasculogenesis properties was also considered both in vitro and in xenografts. Serum glucose, urea, transaminase levels, as well as other signs of distress were checked in mice treated with the IGF-IR inhibitor. Results: Significant inhibition of migration, metastasis, vasculogenicity, and angiogenesis was recorded after treatment of Ewings sarcoma cells with NVP-AEW541. In view of its application and the similarity of insulin receptor and IGF-IR, diabetogenic side effects were considered. We observed a significant decrease of glucose blood serum due to increased glucose uptake at cellular level and an increase in urea concentration. Moreover, an initial weight loss was observed in mice bearing tumors. All these side effects were similarly detected in mice treated with vincristine. After the first days of treatment, all the animals started to grow again. Conclusions: Our results globally reinforce the idea that IGF-IR inhibitor NVP-AEW541 could have a role in future combined therapies and suggest to pursue a thorough molecular analysis of the metabolic activity of IGF-IR to avoid possible side effects of these inhibitors.

Predictive role of positron emission tomography (PET) in the outcome of lymphoma patients

An extensive analysis of the reliability of positron emission tomography (PET) after induction treatment in patients with Hodgkins disease (HD) or aggressive non-Hodgkins lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or aggressive NHL (n=34) were studied with both PET and CT scans following standard chemotherapy induction therapy (ABVD or MACOP-B) with/without radiotherapy. Histopathological analysis was performed when considered necessary. After treatment, four out of five (80%) patients who were PET+/CT− relapsed, as compared with zero out of 29 patients in the PET−/CT− subset. Among the 41 CT+ patients, 10 out of 11 (91%) who were PET+ relapsed, as compared with 0 out of 30 who were PET−. The actuarial relapse-free survival (RFS) rates were 9 and 100% in the PET+ and PET− subsets, respectively (P=0.00001). All five patients who were PET+/CT− underwent a lymph node biopsy: in four (80%) cases, persistent lymphoma and was confirmed at histopathological examination. Two HD patients who were PET−/CT+ (with large residual masses in the mediastinum or lung) were submitted to biopsy, which in both cases revealed only fibrosis. In HD and aggressive NHL patients, PET positivity after induction treatment is highly predictive for the presence of residual disease, with significant differences being observable in terms of RFS. PET negativity at restaging strongly suggests the absence of active disease; histopathological verification is important in patients who show PET positivity.

Role of 11C-choline PET/CT in the re-staging of prostate cancer patients with biochemical relapse and negative results at bone scintigraphy

AIM to evaluate the utility of (11)C-choline PET/CT in prostate cancer (PC) patients who have demonstrated a biochemical recurrence and a negative bone scintigraphy (BS). MATERIALS AND METHODS 123 consecutive PC patients (mean age 67.6 years; range 54-83) with a biochemical relapse (mean PSA value 3.3ng/mL; range 0.2-25.5) after radical prostatectomy (RP) were included in our retrospective study. Patients underwent a BS that resulted negative and a (11)C-choline PET/CT within 4 months from BS (range: 1 day to 4 months; mean: 2.5 months). Validation of results was established by: (1) a positive biopsy, (2) a positive subsequent BS, CT or MR and (3) a normalization of (11)C-choline uptake after systemic therapy or a progression of the disease. RESULTS (11)C-choline PET/CT was positive in 42/123 patients (34.1%). (11)C-choline PET/CT detected lesions in: bone (10 patients), lymph-nodes (20 patients), bone and lymph nodes (7 patients), bone and lung (1 patient), lymph-nodes and lung (1 patient), local relapse (3 patients). Overall, (11)C-choline PET/CT showed a total of 30 unknown bone lesions in 18/123 (14.6%) patients. CONCLUSION (11)C-choline PET/CT showed a better sensitivity than BS in patients with biochemical relapse after RP: (11)C-choline PET/CT detected unknown bone lesions in 18/123 (14.6%) patients.

PET/CT imaging in different types of lung cancer: An overview

Lung cancer (LC) still represents one of the most common tumours in both women and men. PET/CT is a whole-body non-invasive imaging procedure that has been increasingly used for the assessment of LC patients. In particular, PET/CT added value to CT is mainly related to a more accurate staging of nodal and metastatic sites and to the evaluation of the response to therapy. Although the most common PET tracer for LC evaluation is 18F-FDG, new tracers have been proposed for the evaluation of lung neuroendocrine tumours (68Ga-DOTA-peptides, 18F-DOPA) and for the assessment of central nervous system metastasis (11C-methionine). This review focuses on the main clinical applications and accuracy of PET/CT for the detection of non-small cells lung cancer (NSCLC), broncho-alveolar carcinoma (BAC), small cells lung cancer (SCLC), lung neuroendocrine tumours (NET) and solitary pulmonary nodules (SPN).

68Ga-Citrate PET/CT for Evaluating Patients with Infections of the Bone: Preliminary Results

The aim of this work was to preliminarily evaluate the sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of 68Ga-citrate PET/CT in a population of patients with suspected bone infections. Methods: We enrolled 31 patients with suspected osteomyelitis or diskitis who underwent a total of forty 68Ga-citrate PET/CT scans. The results were compared with different combinations of diagnostic procedures (MRI, radiography, CT, or white blood cell scintigraphy), biopsy (when diagnostic), and follow-up data (at least 1 y) to determine the performance of 68Ga-citrate PET/CT. Results: We found a sensitivity of 100%, a specificity of 76%, a positive predictive value of 85%, a negative predictive value of 100%, and an overall accuracy of 90%. Conclusion: Although preliminary, these data confirm a possible role for 68Ga-citrate in the diagnosis of bone infections, especially in consideration of its favorable characteristics.