Vincenzo Allegri

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.

68ga-dota-noc: a new Pet tracer for evaluating patients with bronchial carcinoid

BackgroundConventional imaging techniques [computed tomography (CT), ultrasound, magnetic resonance] and somatostatin receptor scintigraphy are often insufficient to make a conclusive diagnosis of bronchial carcinoid (BC). PET is commonly used for the assessment of lung cancer but 18F-fluorodeoxyglucose, the most frequently used PET tracer, presents a low sensitivity for the detection of neuroendocrine tumours (NETs). New PET radiopharmaceuticals such as 68Ga-DOTA peptides, which directly bind to somatostatin receptors and are usually expressed on NET cell surfaces, have been reported to be superior to both morphological and somatostatin receptor scintigraphy imaging for gastroenteropancreatic NETs. However, their role in BC has never been evaluated. Our aim is to evaluate the role of 68Ga-DOTA-NOC (68Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide) PET for the assessment of BC patients. MethodsTen patients with pathologically proven well-differentiated BC and one patient with highly suggestive CT images for BC were studied by 68Ga-DOTA-NOC PET/CT. PET findings were compared with clinical follow-up, pathology and contrast-enhanced CT findings. Results68Ga-DOTA-NOC PET/CT detected at least one lesion in nine of 11 patients and was negative in two. PET/CT and contrast-enhanced CT were discordant in eight of 11 patients, whereas in only three patients both provided similar results. PET/CT detected a higher number of lesions in five patients and excluded malignancy at sites considered positive on CT in three of 11; follow-up confirmed PET/CT findings in all patients. In PET/CT-positive patients, the mean maximal standardized uptake value was 25.9 [4.4–60.5]. On a clinical basis, PET/CT provided additional information in nine of 11 patients leading to the changes in the clinical management of three of nine patients. ConclusionPET/CT with 68Ga-DOTA-NOC was useful in BC patients because it led to a better evaluation of the extent of the disease.

Evaluation of unusual neuroendocrine tumours by means of 68Ga-DOTA-NOC PET

(18)F-FDG PET value for the assessment of neuroendocrine tumours (NET) is limited. Preliminary studies indicate that somatostatin receptor PET using (68)Ga-DOTA-peptides is more accurate for disease assessment and provide additional data on receptor status, that are crucial for targeted radionuclide therapy. At present, however, few papers investigated the role of (68)Ga-DOTA-NOC PET in NET, especially in unusual situations. The purpose of the present study was to evaluate (68)Ga-DOTA-NOC for the evaluation of NET of uncommon presentation. Patients with biopsy-proven NET were scheduled for (68)Ga-DOTA-NOC PET; we excluded from further evaluation cases with most common NET tumours (gastro-entero-pancreatic and pulmonary localization of primary lesion, MEN syndromes, medullary thyroid carcinoma, pheochromocytomas). PET results were compared with findings of conventional imaging, including CT, ultrasonography, MR and somatostatin receptor scintigraphy; finally PET results were compared with follow-up data with respect to the impact on patient management. Fourteen patients were finally enrolled; primary tumours were located at uterine level (3 cases), prostate (3 cases), ovary (1 case), kidney (1 case), breast (1 case), ear (1 case); also 3 cases of paraganglioma (at neck, abdominal and mediastinum level) and 1 case of lymphoma were included. (68)Ga-DOTA-NOC PET was positive, showing at least 1 lesion, in 6/14 cases while 5 cases turned out negative and 2 inconclusive. On a clinical basis, (68)Ga-DOTA-NOC provided additional information in comparison to conventional imaging procedures in 7/14 cases, and was considered useful in 12/14 patients, with 8 patients in which (68)Ga-DOTA-NOC PET was determinant for patients management. Although the number of patients studied is limited, our data show that (68)Ga-DOTA-NOC can be usefully applied for the evaluation of NET of uncommon presentation; in particular very promising results were obtained in paraganglioma. On the other hand, care has to be paid when studying lesions localized at sites of physiological concentration of the tracer, and in presence of inflammation.

FDG-PET/CT in advanced ovarian cancer staging: Value and pitfalls in detecting lesions in different abdominal and pelvic quadrants compared with laparoscopy

INTRODUCTION AND AIM Ovarian carcinoma (OC) is a common cancer in the Western Countries, and an important cause of death in patients suffering with gynaecologic malignancies. The majority of patients present with advanced disease at the time of diagnosis. Treatment with debulking surgery followed by chemotherapy is the standard approach while chemotherapy is contemplated when surgery is not possible. A correct pre-operative staging is important to ensure a most appropriate management. Laparoscopy (LPS) is the standard diagnostic tool for the assessment of intraperitoneal infiltration but is invasive and requires general anaesthesia. FDG-PET/CT is increasingly used for staging different types of cancer, and the aim of this study is to assess the value of FDG-PET/CT in staging advanced OC and its sensitivity to detect lesions in different quadrants of the abdominal-pelvic area compared to laparoscopy. MATERIALS AND METHODS From September 2004 till April 2008, 40 patients with high suspicion of OC were referred to our hospital for diagnostic LPS to explore the possibility of optimal debulking surgery. Those who were not suitable for surgery were referred for chemotherapy. Before chemotherapy, the patients underwent an FDG-PET/CT scan. The findings in 9 quadrants of abdominal-pelvic area (total 360 quadrants) for PET/CT and LPS were recorded and compared. RESULTS In 14/360 areas (3.8%), surgical evaluation was not possible because of presence of adhesions, thus the number of areas explored by laparoscopy was 346. Tumour was found in 308 quadrants (38 quadrants free of disease). PET/CT was positive in all 40 patients with true negative results in 26/346 quadrants (7.5%), and true positives results in 243/346 quadrants (70.2%). False positive and negative PET/CT results were found in 12/346 and 65/346 quadrants, respectively. False positive PET/CT findings were evenly present in all quadrants. False negative PET/CT findings were present in 31/109 (28.4%) upper abdominal quadrants (epigastrium and diaphragmatic areas). Final analysis showed a sensitivity and specificity for PET/TC of 78.9 and 68.4% respectively with a positive predictive value of 95.3%. A significant difference was noted between mean SUVmax associated with lesions smaller or larger than 0.5 cm (p=0.006). CONCLUSION Our results suggest that PET/CT may prove a useful tool for pre-surgical staging of ovarian cancer with a sensitivity and specificity of 78 and 68%, respectively. However, it may be used in combination with laparoscopy for better results. PET/CT showed an adequate correlation between SUVmax values and laparoscopy findings of lesions>5mm, but a high rate of false negative results in lesions<5mm such as in carcinomatosis. PET/CT should be used carefully in early stage disease, with low risk of peritoneal infiltration, because of high rate of false positive results, to avoid unnecessary therapy procedures.

68Ga-DOTANOC PET/CT Allows Somatostatin Receptor Imaging in Idiopathic Pulmonary Fibrosis: Preliminary Results

Interstitial lung diseases include different clinical entities with variable prognoses. Idiopathic pulmonary fibrosis (IPF), the most common, presents the most severe outcome (death within 3–5 y), whereas nonspecific interstitial pneumonia (NSIP) shows a more indolent progression. Preclinical evidence of somatostatin receptor (SSTR) expression on fibroblasts in vitro and in lung fibrosis murine models, coupled with the longer survival of mice with fibrotic lungs treated with agents blocking SSTR, supports the hypothesis of imaging fibroblast activity in vivo by visualization of SSTR with 68Ga-DOTANOC PET/CT. The aim of this study was to evaluate 68Ga-DOTANOC PET/CT in patients with IPF and NSIP. Methods: Seven IPF patients and 7 NSIP patients were included in the study. 68Ga-DOTANOC PET/CT and high-resolution CT (HRCT) were performed in all cases by following a standard procedure. PET/CT results were compared with disease sites and extent on HRCT. Results: In IPF, 68Ga-DOTANOC uptake was peripheral, subpleural, and directly correlated with pathologic areas on HRCT (subpleural/reticular fibrosis, honeycombing). NSIP patients showed fainter tracer uptake, whereas corresponding HRCT showed areas of ground-glass opacity and rare fibrotic changes. Only IPF patients showed a linear correlation between maximal SUV and disease extent quantified both automatically (Q) (IPF: P = 0.002, R = 0.93) and using the visual score (Spearman ρ = 0.46, P = 0.0001). Q directly correlated with percentage carbon monoxide diffusing capacity in IPF (P = 0.03, R = 0.79) and NSIP (P = 0.05, R = 0.94), whereas maximal SUV did not present any correlation with percentage carbon monoxide diffusing capacity. Conclusion: Our preliminary data show that 68Ga-DOTANOC PET/CT demonstrates SSTR overexpression in IPF patients; this may prove interesting for the evaluation of novel treatments with somatostatin analogs.

Prognostic Value of 68Ga-DOTANOC PET/CT SUVmax in Patients with Neuroendocrine Tumors of the Pancreas

This study was performed to investigate the role of 68Ga-DOTANOC SUVmax as a potential prognostic factor in patients with pancreatic neuroendocrine tumor (pNET). Methods: Among the patients who underwent 68Ga-DOTANOC PET/CT, we retrospectively collected the data of those who had G1 or G2 pNET (2010 World Health Organization classification), presented with disease on PET/CT and CT, and had at least 6 mo of follow-up. Patients with multiple endocrine neoplasia were excluded. Results: Overall, 43 patients were included. No significant differences in SUVmax were observed with respect to sex, tumor syndrome, stage, World Health Organization classification, or Ki-67. During follow-up (median, 20 mo), 11 patients (35.6%; median, 33 mo; interquartile range, 20–48 mo) had stable disease and 32 (74.4%; median, 19 mo; interquartile range, 14–26 mo) had progressive disease. SUVmax at 24 mo of follow-up was significantly higher (P = 0.022) in patients with stable disease than in patients with progressive disease. The best SUVmax cutoff ranged from 37.8 to 38.0. The major risk factors for progression included an SUVmax of no more than 37.8 (hazard ratio, 3.09; P = 0.003), a Ki-67 of more than 5% (hazard ratio, 2.89; P = 0.009), and medical therapy alone (hazard ratio, 2.36; P = 0.018). Advanced stage (IV) (P = 0.026), an SUVmax of less than 37.8 (P = 0.043), and medical therapy alone (P = 0.015) were also confirmed at multivariate analysis. Median progression-free survival was 23 mo. Significant differences in progression-free survival were observed in relationship to Ki-67 (median, 45 mo for Ki-67 ≤ 5% and 20 mo for Ki-67 > 5%; P = 0.005), SUVmax (<37.8 vs. >38.0: 16.0 vs. 27.0 mo; P = 0.002), and type of therapy (medical vs. peptide receptor radionuclide therapy: 16.0 vs. 26.0 mo; P = 0.014). Conclusion: 68Ga-DOTANOC SUVmax is a relevant prognostic factor in patients with G1 and G2 pNET, and its routine use will improve disease characterization and management in these patients, who may present with atypical cases showing heterogeneous clinical behavior.

68Ga-DOTA-NOC PET/CT detects somatostatin receptors expression in von hippel-lindau cerebellar disease.

A case of Von-Hippel Lindau (VHL) disease has been studied using 68Ga-DOTA-NOC PET/CT. PET/CT demonstrated the presence of somatostatin receptors within 2 focal areas in the cerebellum corresponding to the lesions detected by MRI. Considering the heterogeneous lesions localizations in VHL disease, PET/CT may be a useful imaging modality for diagnosing lesions of central nervous system and neuroendocrine lesions and for direct demonstration of somatostatin receptors for targeted treatment.

Peptide Receptor Radionuclide Therapy in a Case of Multiple Spinal Canal and Cranial Paragangliomas

Case Report In 2000, a 32-year-old man was admitted to the hospital with lower back pain. Gadolinium-enhanced lumbar (L1-S1) magnetic resonance imaging (MRI) revealed a clearly delimited, ovoid, expansive, intradural mass with a strong contrast enhancement behind the L4 vertebral body, occupying the vertebral foramina, mildly scalloping the vertebral body. MRI findings were interpreted as caudal ependymoma. After radical surgery, the symptoms vanished. The tumor mass measured 3 2.5 2 cm and had a yellowish brown cut surface with hemorrhagic and cystic foci. The specimens were fixed in 10% buffered formalin and embedded in paraffin. Sections (3 m thick) were stainedwithhematoxylinandeosin(Fig1A; 10),Grimelius Masson trichrome (Bio-Optica, Milano, Italy), and periodic acid-Schiff (PAS; Merck, Darmstadt, Germany). Immunohistochemical analyses were carried out by using synaptophysin (Fig 1B; 10; positive stain), CD56 (Fig 1C; 20; positive stain), avidin-biotin complex method for low-molecular-weight cytokeratin (Fig 1D; 10; punctiform expression of anticytokeratin marker [CAM 5.2]), somatostatin, serotonin, neuronspecific enolase, Leu-7, inhibin, and S-100 protein. A positive SDHB immunohistochemistry (Fig 1E; 10) was also reported. At light microscopy, the tumors presented as solid proliferation of round cells with eosinophilic cytoplasm and regular, monomorphic, oval central nuclei in an alveolar arrangement (Zellballen pattern) surrounded by thin capillaries and a flattened layer of sustentacular cells. Pleomorphism, mitotic figures, and bizarre nuclear forms were occasionally seen. Positive expression of chromogranin A and synaptophysin and the presence of chief (type 1) cells were consistent with the neuroendocrine nature of the tumor. Few sustentacular cells were positive for S-100 protein, and immunoreactivity for glial

Pretherapeutic dosimetry in patients affected by metastatic thyroid cancer using 124I PET/CT sequential scans for 131I treatment planning.

Purpose This study evaluates the use of sequential 124I PET/CT for predicting absorbed doses to metastatic lesions in patients with differentiated thyroid cancer undergoing 131I therapy. Methods From July 2011 until July 2013, 30 patients with metastatic differentiated thyroid cancer were enrolled. Each participant underwent PET/CT at 4, 24, 48, and 72 hours with 74 MBq of 124I. Blood samples and whole-body exposure measurements were obtained to calculate blood and red marrow doses. Activity concentrations and lesion volumes obtained from PET/CT were used to evaluate tumor doses with medical internal radiation dose formalism and spheres modeling. Mean administered 131I therapeutic dose was 5994 MBq (range, 1953–11,455 MBq). Results 124I PET/CT demonstrated all lesions detected by posttherapy 131I whole-body scans. Mean dose rates for blood, red marrow, and lesions were as follows: 0.07 ± 0.02 mGy/MBq, 0.05 ± 0.02 mGy/MBq, and 46.5 ± 117 mGy/MBq, respectively. Despite the high level of thyroid-stimulating hormone and CT detectable lesions, 15 of 30 patients did not show any abnormal 124I uptake. Conclusions The quantitative value of 124I PET/CT allows simple and accurate evaluation of lesion dosimetry following medical internal radiation dose formalism. Negative 124I PET/CT predicts absence of iodine avidity, potentially allowing avoidance of therapeutically ineffective 131I administration.

I-123 MIBG scintigraphy and 68Ga-DOTANOC PET/CT negative but F-18 DOPA PET/CT positive pheochromocytoma: a case report.

We observed a 34-year-old man who was incidentally found to have an adrenal mass during surgical follow-up for perforated ulcer. The patient was subjected to I-123 MIBG scintigraphy, 68Ga-DOTANOC PET/CT, and F-18 DOPA PET/CT. Only F-18 DOPA PET/CT showed evidence of an avid adrenal mass. A CT-guided biopsy was performed and it was suggestive for pheochromocytoma. He underwent surgery and a pheochromocytoma, about 40 mm in diameter, was detected. Traditionally, I-123 MIBG scintigraphy has been used in detecting chromaffin cell tumors, but more recently it had been demonstrated that a certain part of pheochromocytoma could be false-negative on scintigraphy.