Standardized uptake values of (68)Ga-DOTANOC PET: a promising prognostic tool in neuroendocrine tumors.

UNLABELLED: Despite the fact that several studies have been published regarding the prognostic factors of neuroendocrine tumors (NETs), there are some cases in which available data are not sufficient to predict disease progression and to define a correct therapeutic approach. To our knowledge, the role of maximum standardized uptake value (SUVmax) as a prognostic factor has never been studied in NET patients. Therefore, we prospectively investigated whether (68)Ga-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-octreotide ((68)Ga-DOTANOC) PET SUVmax could be used as an accurate noninvasive marker for disease prognosis. METHODS: Forty-seven patients with NETs were studied with (68)Ga-DOTANOC PET. All patients underwent a baseline visit and laboratory and radiologic examinations. Follow-up was performed in all cases. RESULTS: SUVmax was significantly higher in patients with pancreatic NET and in those with well-differentiated NETs. Moreover, SUVmax was significantly higher in patients with an elevated expression of 2A-somatostatin receptor. During the follow-up, the disease was stable or presented a partial response in 25 patients, and in 19 cases the disease progressed. The patients with stable disease or a partial response had an SUVmax significantly higher than did those in the progressive disease group, with the best cutoff ranging from 17.9 to 19.3. At univariate and multivariate analysis, the significant positive prognostic factors were well-differentiated NET, an SUVmax of 19.3 or more, and a combined treatment with long-acting somatostatin analogs and radiolabeled somatostatin analogs. CONCLUSION: We demonstrated, for the first time to our knowledge, that (68)Ga-DOTANOC PET SUVmax correlates with the clinical and pathologic features of NETs and is also an accurate prognostic index.

(68)Ga-DOTA-NOC PET/CT in comparison with CT for the detection of bone metastasis in patients with neuroendocrine tumours.

PURPOSE: To retrospectively evaluate the sensitivity, specificity and accuracy of (68)Ga-DOTA-NOC PET/CT and CT alone for the evaluation of bone metastasis in patients with neuroendocrine tumour (NET). METHODS: From among patients with NET who underwent (68)Ga-DOTA-NOC PET/CT between April 2006 and November 2008 in our centre, 223 were included in the study. Criteria for inclusion were pathological confirmation of NET and a follow-up period of at least 10 months. PET and CT images were retrospectively reviewed by two nuclear medicine specialists and two radiologists, respectively, without knowledge of the patient history or the findings of other imaging modalities. PET data were compared with the CT findings. Interobserver agreement was evaluated in terms of the kappa score. Clinical and imaging follow-up were used as the standard of reference to evaluate the PET findings. RESULTS: PET was performed for staging (49/223), unknown primary tumour detection (24/223), restaging (32/223), restaging before radioimmunotherapy (1/223), evaluation during therapy (12/223), equivocal findings on conventional imaging (4/223 at the bone level; 61/223 at sites other than bone), and follow-up (40/223). A very high interobserver agreement was observed. CT detected at least one bone lesion in only 35 of 44 patients with a positive PET scan. In particular, PET showed more lesions in 20/35 patients, a lower number of lesions in 8/35, and the same number in 7/35. The characteristics of the lesions (sclerotic, lytic, mixed) on the basis of the CT report did not influence PET reading. PET revealed the presence of at least one bone metastasis in nine patients with a negative CT scan. Considering patients with a negative PET scan (179), CT showed equivocal findings at the bone level in three (single small sclerotic abnormality in two at the spine level, and bilateral small sclerotic abnormalities in the humeri, femurs and scapula). Clinical follow-up confirmed the PET findings in all patients; thus there were no false-positive or false-negative findings. Considering all patients, PET detected more lesions than CT (246 vs. 194). As compared to CT, on a patient basis PET showed a higher sensitivity (100% vs. 80%), specificity (100% vs. 98%), positive predictive value (100% vs. 92%), and negative predictive value (100% vs. 95%). CONCLUSION: In conclusion, (68)Ga DOTA-NOC PET was more accurate than CT for the identification of bone lesions and led to a change in clinical management in nine patients with a negative CT scan.

C-11 acetate does not enhance usefulness of F-18 FDG PET/CT in differentiating between focal nodular hyperplasia and hepatic adenoma.

PURPOSE OF THE REPORT: We assessed the usefulness of F-18 fluorodeoxyglucose positron emission tomography (FDG PET) and C-11 acetate PET (AC PET) in distinguishing hepatic lesions due to consequential disease (hepatocellular adenoma and malignant lesions) from focal nodular hyperplasia (FNH) in patients at low risk of malignancy. MATERIALS AND METHODS: Thirty-one patients with 43 lesions were prospectively enrolled. The diagnostic work-up included Doppler and contrast-enhanced ultrasonography, contrast-enhanced computed tomography, and/or magnetic resonance imaging. Fine needle biopsy was performed if the imaging study was inconclusive. The work-up revealed 36 FNH and 7 consequential lesions (5 hepatocellular adenoma, 1 hepatoma, and 1 metastasis). All patients underwent FDG and AC PET. FDG PET with target/background ratio (T/Br) greater than 1.2 and AC PET with T/Br of less than 1.2 were considered positive test for consequential disease. RESULTS: On FDG PET, we had 6 true-positive out of 7 lesions due to consequential diseases, with a sensitivity of 85.7%, and 33 true-negative out of 36 lesions with FNH, with a specificity of 91.7%. Using AC PET, there were 2 true-positive lesions out of 7 caused by neoplasms, with a sensitivity of 28.6%, and 34 true-negative lesions out of 36 FNH, with a specificity of 94.4%. CONCLUSIONS: When the goal is differentiating FNH from liver neoplasms, AC PET offered no additional diagnostic advantage over what is achieved with FDG PET.

Late FDG PET normalization after radioimmunotherapy in a patient with non-Hodgkin lymphoma.

Fluoro-deoxy-glucose positron emission tomography (FDG PET) has largely been used for response assessment after treatment of lymphoma, resulting in a very sensitive and specific imaging technique for the detection of residual disease. For this reason FDG PET has recently been proposed to be integrated in the International Workshop Criteria. In this report, a patient with non-Hodgkin lymphoma was treated with radioimmunotherapy for disease relapse, demonstrated by PET. Post-treatment evaluation was performed 9 weeks after treatment, and PET showed almost complete disappearance of tracer uptake, but with faint persistence of uptake at 1 iliac node and thus was a suspect for residual disease. However, a wait-and-see approach was decided and the patient was rescanned with PET 18 weeks after treatment, and the results were finally negative. This case indicates that after completion of radioimmunotherapy it may be recommended to wait several weeks before performing a PET scan and, in case of minimal findings, to consider a short-term re-evaluation.

Small animal PET in oncology: the road from bench to bedside.

Positron emission tomography (PET) is routinely performed in patients with cancer for disease staging, assessment of relapse, and evaluation of therapy response. In addition to its well-established value in human malignant diseases, the use of special small animal PET (SA-PET) scanners have allowed for accurate assessment of small animals bearing human tumors. This application of PET provides whole-body, noninvasive, functional data of tumor lesions and can be used to assess abnormalities in the metabolic pathways of cancer, such as uncontrolled proliferation, increased apoptosis, and angiogenesis. Several positron-emitting tracers labeled with 18-fluorine and 11-carbon are currently available for PET studies to image abnormal biologic pathways of tumors. Moreover, SA-PET can be used to evaluate tumor-cell-receptor expression, a sign of tumor cells differentiation that is relevant for planning targeted therapies. Another advantage of SA-PET is the quantitation capability: Semiquantitation of the tumor activity can be performed at each scan and compared in the same animal over time to monitor tumor growth or to assess the response to new therapies. This review focuses on the applications of SA-PET for the visualization of the pathophysiologic pathways of tumor cells.

68Ga-DOTA-NOC: a new PET tracer for evaluating patients with bronchial carcinoid.

BACKGROUND: Conventional 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. METHODS: Ten 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. RESULTS: 68Ga-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. CONCLUSION: PET/CT with Ga-DOTA-NOC was useful in BC patients because it led to a better evaluation of the extent of the disease.

The impact of antithrombotic prophylaxis on infectious complications in cancer patients with central venous catheters: an observational study.

Infections in cancer patients after implantation of a central venous device (CVD) are not infrequent and are potentially serious. The possibility of limiting this complication with antithrombotic drugs is still debated. For this observational study, we recorded the routine management of CVD in cancer patients in 18 oncology centers in Lombardy (northern Italy), assessing the effect of antithrombotic prophylaxis on catheter-related infections. Out of 1410 patients enrolled, 451 received antithrombotic prophylaxis continuously after implantation of the central line. During a median follow-up of 30 months, 57 catheter-related infections were reported in the 1390 patients seen at least once at follow-up visits (4.1% of the whole series), giving an overall incidence of 0.10 infections per 1000 catheter days. This complication was significantly more frequent among patients with an indwelling central venous catheter, or peripherally inserted catheter, than among those with a port device, and the group not given antithrombotic prophylaxis had 0.14 infective complications/1000 CVD days compared with 0.05/1000 CVD days (odds ratio 2.4; 95% confidence interval 1.7-5.0) for those treated. Antithrombotic prophylaxis protected against infections at the catheter exit site and track but not against systemic infections. Confirming earlier evidence, this study found a reduction in catheter-related infections in patients given antithrombotic prophylaxis. However, this reduction, reflecting local infections, seems unlikely to be one of the mechanisms explaining the lower mortality among our patients treated with anticoagulants.

18F-FDG PET/CT in myeloma with presumed solitary plasmocytoma of bone.

AIM: To evaluate the value of 18F-fluorodeoxy-glucose (FDG) positron emission tomography with computed tomography (PET/CT) in myeloma in patients presenting with a solitary plasmacytoma of bone (SPB). PATIENTS AND METHODS: Fourteen consecutive patients studied since 2006, all having a diagnosis of SPB before PET/CT imaging took part in this study. In 3 patients PET/CT was performed for staging while in the remaining 11 it was used to monitor therapy. PET/CT was performed using a dedicated tomograph 60-90 minutes after intravenous injection of 53 MBq/kg of 18F-FDG and the results were compared to other diagnostic procedures [radiographs and magnetic resonance imaging (MRI)], biopsy, and other available follow-up data. RESULTS: In 8/14 patients, PET/CT scans showed previously unsuspected sites of increased FDG accumulation. In 6/8 patients, FDG uptake was considered pathologic, depicting myeloma involvement in bone, while in the remaining cases, findings were considered incidental and not related to myeloma. PET findings attributed to myeloma were confirmed (i.e. true positives) in 6/6 cases (100%) and in all patients with findings reported as non-pathologic, myeloma was excluded (100% true negatives). CONCLUSION: Our preliminary data in a small number of cases suggests that there are a group of patients with SPB (local disease) in whom FDG PET/CT may detect other unsuspected sites of bone involvement, upstaging the extent of the disease. In these cases, SPB may be a local manifestation of multiple myeloma where other sites of involvement have eluded detection by other less sensitive imaging modalities (i.e. skeletal surveys) or anatomically restricted imaging (i.e., less than total body MR or CT). Finding other sites of involvement have significant implications for appropriate treatment of myeloma.

Early relapse in a patient with Hodgkin's disease and negative interim FDG-PET.

The role of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the assessment of lymphoma patients is well established, and PET is routinely used for initial staging, early evaluation of treatment response, and identification of disease relapse. The early evaluation of response to therapy (interim PET) has been reported to be an accurate predictor of progression-free survival, and end-treatment PET has been suggested to be unnecessary if interim PET results are negative. We report on a patient with Hodgkin's disease with a positive PET scan at presentation and a negative interim PET (carried out after three cycles of adriamycin, bleomycin, vinblastine, and dacarbazine; ABVD). Despite uncomplicated clinical course, end-treatment PET (following six cycles) was positive, showing a very early relapse. For this reason, patient underwent further treatment; however, a complete remission was not obtained, and a poor prognosis is expected. This case testifies the possibility of early relapse of lymphoma even in the case of negative interim PET; it also supports the usefulness of end-treatment PET scan in lymphoma patients.

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

PURPOSE: (18)F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that (18)F-DOPA and (68)Ga-DOTA-NOC are more accurate for disease assessment and (68)Ga-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. AIM: The aim of this study was to compare (68)Ga-DOTA-NOC and (18)F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. MATERIALS AND METHODS: Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for (18)F-DOPA and (68)Ga-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). RESULTS: The 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. (68)Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while (18)F-DOPA PET was positive in 9/13. On a lesions basis, (68)Ga-DOTA-NOC identified more lesions than (18)F-DOPA (71 vs 45), especially at liver, lung and lymph node level. (68)Ga-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 (18)F-DOPA identified the primary only in two of eight cases. CONCLUSIONS: Although the patients studied are few and heterogeneous, our data show that (68)Ga-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 (18)F-DOPA.

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 patient's 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.

Assessment of a chemically induced model of lung squamous cell carcinoma in mice by 18F-FDG small-animal PET.

BACKGROUND: Small-animal imaging has become a relevant research field in pre-clinical oncology. In particular, metabolic information provided by small-animal positron emission tomography (PET) is very useful to closely monitor tumour growth and assess therapy response in murine models of human disease. There are various murine models for human lung adenocarcinoma, but those for squamous cell lung carcinoma, the most common form of human cancer, are lacking. AIM: To assess the feasibility of 18F-FDG small-animal PET to monitor tumour growth in a chemically induced model of squamous cell carcinoma of the lung. MATERIALS AND METHODS: Nineteen NIH Swiss mice were skin painted by N-nitroso-tris-chloroethylurea (NTCU) twice a week, with a 3 day interval, for 8 months and 10 NIH Swiss mice skin painted with NTCU solvent (acetone) were used as controls. 18F-FDG PET was performed under sevofluorane anaesthesia and oxygen supplementation at 2, 4, 6 and 8 months from initial treatment. Images were assessed by visual analysis and semi-quantitatively. When a diffuse distribution of tumour was noted, the mean of the counts/pixel measured at three lung levels, corrected for the effective dose injected and for decay, was used for comparison between mutagen-painted and control mice. Pathological evaluation was carried out from the time of the first positive PET results in a subgroup of the whole population to assess correlation with PET findings. Small animal CT was performed at 8 months in another subgroup. RESULTS: In both terms of visual analysis and measurement of total lung activity, 18F-FDG PET at 2 and 4 months from initial treatment were comparable in mutagen-painted and controls. At 6 months, PET images showed a faint and diffuse uptake over both lung fields in mutagen-painted mice with multiple focal areas of increased tracer uptake that merged into confluent masses at 8 months and seriously subverting lung architecture on computed tomography. Total lung activity was significantly higher in mutagen-painted versus control mice at 6 (P=0.00000668) and 8 months (P=0.00000043) from initial treatment and paralleled the progressive lung involvement and histological severity. CONCLUSIONS: 18F-FDG PET may be useful in the assessment of this chemically induced murine model of lung squamous cells carcinoma. The total lung activity may be used as a measure of tumour metabolic activity of the tumour-bearing animals and may be useful in new drug testing studies.

11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma.

BACKGROUND: Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. AIM: As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. METHODS: Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. RESULTS: Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). CONCLUSION: According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.

Role of 18F-dopa PET/CT imaging in the management of patients with 111In-pentetreotide negative GEP tumours.

PURPOSE: To assess whether 18F-dopa PET/CT is able to provide information relevant in changing the clinical management of patients with gastro-enteropancreatic (GEP) tumours where there is negative or inconclusive conventional radiological imaging (ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI)) and 111In-pentetreotide scintigraphy. MATERIALS AND METHODS: From January 2005 to October 2006, 84 patients with clinical and biochemical suspicion of GEP tumours were investigated by US and CT scans, MRI and 111In-pentetreotide scintigraphy. In 13/84 (15.4%) both conventional radiological imaging and 111In-pentetreotide scintigraphy provided negative or inconclusive findings, and patients were referred for 18F-dopa PET/CT imaging. Each patient received 5.3 MBq x kg(-1) 18F-dopa intravenously, and imaged 60 min later using a hybrid PET/CT scanner. RESULTS: 18F-dopa PET/CT detected the primary tumour in all 13 patients (size range, 7-26 mm, mean, 18 mm; SUVmax range, 2.3-16.3, mean, 5.7) and further 12 unsuspected lesions (size range, 12-23 mm, mean 17; SUVmax range 2.8-12.7, mean 4.6). Confirmation of the PET/CT findings was obtained in all patients from histopathological analysis of tissue obtained after surgery and/or biopsy. All the 18F-dopa-positive primary lesions were confirmed as being the primary tumour at histology, whereas of the other 12 unsuspected 18F-dopa-positive lesions, 11 were found to be metastatic deposits and one due to unspecific inflammation (one false positive result). Notably, the results of 18F-dopa PET/CT imaging changed the clinical management in 11/13 patients (84%). CONCLUSIONS: Our preliminary results suggest that 18F-dopa PET/CT has a promising role in GEP patients with negative or inconclusive findings at conventional radiological imaging and 111In-pentetreotide scintigraphy. The findings were helpful in biopsy guidance and played a major role in changing the management of those patients.

FDG small animal PET permits early detection of malignant cells in a xenograft murine model.

PURPOSE: The administration of new anticancer drugs in animal models is the first step from in vitro to in vivo pre-clinical protocols. At this stage it is crucial to ensure that cells are in the logarithmic phase of growth and to avoid vascular impairment, which can cause inhomogeneous distribution of the drug within the tumour and thus lead to bias in the final analysis of efficacy. In subcutaneous xenograft murine models, positivity for cancer is visually recognisable 2-3 weeks after inoculation, when a certain amount of necrosis is usually already present. The aim of this study was to evaluate the accuracy of FDG small animal PET for the early detection of malignant masses in a xenograft murine model of human rhabdomyosarcoma. A second goal was to analyse the metabolic behaviour of this xenograft tumour over time. METHODS: We studied 23 nude mice, in which 7 x 10(6) rhabdomyosarcoma cells (RH-30 cell line) were injected in the dorsal subcutaneous tissues. Each animal underwent four FDG PET scans (GE, eXplore Vista DR) under gas anaesthesia. The animals were studied 2, 5, 14 and 20 days after inoculation. We administered 20 MBq of FDG via the tail vein. Uptake time was 60 min, and acquisition time, 20 min. Images were reconstructed with OSEM 2D iterative reconstruction and the target to background ratio (TBR) was calculated for each tumour. Normal subcutaneous tissue had a TBR of 0.3. Necrosis was diagnosed when one or more cold areas were present within the mass. All the animals were sacrificed and histology was available to verify PET results. PET results were concordant with the findings of necropsy and histology in all cases. RESULTS: The incidence of the tumour was 69.6% (16/23 animals); seven animals did not develop a malignant mass. Ten of the 23 animals had a positive PET scan 2 days after inoculation. Nine of these ten animals developed a tumour; the remaining animal became negative, at the third scan. The positive predictive value of the early PET scan was 90% (9/10 animals) while the negative predictive value was 46% (6/13 animals). In the whole group of animals, mean TBR increased scan by scan. There was a statistically significant difference in TBR between 2 and 20 days after inoculation. Necrosis was present at the second scan in two animals, at the third scan in six animals and at the fourth scan in 11 animals. CONCLUSION: The high positive predictive value of FDG PET 2 days after inoculation means that an animal with a first positive scan has a very high likelihood of developing a mass and can be treated at an early stage with an experimental drug. Animals negative at this point in time will never develop a mass or will eventually do so at a late phase. As 2 of the 16 (12.5%) positive animals had necrosis at the second scan, indicating a vascular mismatch, it may be argued that animals should be treated 2 days after inoculation to guarantee homogeneous vascularisation (thereby ensuring a good drug supply within the tumour) in all subjects.

18F-FDG PET in mucosa-associated lymphoid tissue (MALT) lymphoma.

To evaluate the sensitivity of 18-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) in patients with mucosa-associated lymphoid tissue (MALT) lymphoma. A total of 32 patients with a histological diagnosis of extra-nodal MALT lymphoma were referred to the PET Centers in the last 2 years (2003 - 2004) and scanned with 18F-FDG-PET following standard procedures. Overall, the results of 50 18F-FDG-PET scans performed in either active disease state or in complete remission were reviewed. Sites of primary disease included stomach, lung, parotid, skin, orbit, mandible, esophagus and uterus. This study retrospectively enrolled 26 patients with known active disease. 18F-FDG-PET was true positive (TP) in 21/26 patients and false negative (FN) in 5/26. Sensitivity of 18F FDG-PET for extra-nodal MALT was 81%. The data show that 18FDG-PET is a useful diagnostic tool in order to stage, restage or monitor disease in patients with extra-nodal MALT lymphoma.

Role of 18F-FDG-PET and PET/CT imaging in thyroid cancer.

In patients affected by differentiated thyroid cancer (DTC), the lacking of 131Iodine trapping by metastatic tissue does not allow 131Iodine whole body scintigraphy to visualize matastatic spread as well as the use of 131Iodine therapy to cure such metastatic spread. Prognosis of 131Iodine-negative DTC metastasis, so-called non-functioning metastasis, is significantly worst. In these patients an early diagnosis of non-functioning metastasis and their surgical extirpation remains the optimal therapeutic approach. In this view, a high sensitive localizing imaging different form 131Iodine whole body scintigraphy is required. Ultrasonography is characterized by a relatively high sensitivity in these patients but it is highly operator-dependent and, moreover, it can be used to explore neck alone. Computed tomography (CT) scan and magnetic resonance (MR) imaging are characterized by a relatively low sensitivity even if they are useful to provide the surgeon with anatomical information of the operating basin. Various tumor-seeking radiotracers have been proposed, mainly using SPECT as 201Thallium, 99mTc-Sestamibi and 99mTc-Tetrofosmin with good results. Even more favorable results have been reported with some positron radiotracers, mainly the 18F-FDG with PET and more recently with PET/CT tomographs. The typical indication to performing with examination is the DTC patient previously treated by total thyroidectomy and 131Iodine ablative therapy, with increased serum thyroglobulin (Tg) or anti-thyroglobulin (TgAb) antibodies during follow-up but with negative 131Iodine whole body scintigraphy even obtained after high, therapeutic 131Iodine doses. Several studies in literature have reported high sensitivity (up to 85%) and specificity (up to 95%) of FDG-PET in metastatic DTC patients. The integrated PET/CT fusion imaging systems, seem able to provide some additional advantages over PET alone, mainly related to a better anatomical localization of the hypermetabolic metastatic lesions. A change in the management of DTC patients affected by non-functioning metastatic spread not visualized by other imaging techniques has been reported in 30% of patients. Lastly, the role of PET and PET/CT fusion imaging systems seem to be promising also in patients affected by medullary thyroid carcinoma (MTC), especially for the detection of neck and mediastinal lesions, with a sensitivity superior to the other currently available imaging methods, however the data reported on medullary cancer are little and further studies are needed to elucidate the preliminary promising results.

Discordant response to chemotherapy: an unusual pattern of fluoro-deoxy-D-glucose uptake in heavily pre-treated lymphoma patients.

In recent years a number of studies have been published showing strong value of positron emission tomography using 18-Fluorine 2-fluoro-deoxy-D-glucose (FDG-PET) in term of diagnosis, response to treatment, disease recurrence and prognostic indicator in early restaging. This study observed 17 patients who presented contemporary disease progression in some localizations as well as regression in others (PROG + REG pattern); this investigation assessed that this unusual pattern of FDG uptake lead to an unfavorable prognosis. Among 1280 FDG-PET scans performed between August 2003 and December 2004 on patients affected by lymphoma with suspected recurrence, attention was focused on 17 patients presenting a PROG + REG pattern. At follow-up (4 months) only 1/17 (6%) patient was in complete remission after salvage therapy, while 6/17 (35%) had stable disease and 10/17 (59%) had rapid progression of the disease. This study further strengthens the role of FDG-PET in lymphoma patients follow-up, as it can provide useful information to better differentiate those cases who may benefit from conventional treatments from others in whom additional treatment would provide avoidable toxicity.

11C-methionine PET/CT in 99mTc-sestamibi-negative hyperparathyroidism in patients with renal failure on chronic haemodialysis.

PURPOSE: Scintigraphic localisation of parathyroid glands is often unsuccessful in patients with renal failure on chronic haemodialysis who have secondary hyperparathyroidism (HPT). The purpose of this study was to investigate the use of (11)C-methionine PET/CT to detect hyperfunctioning parathyroid glands in patients with renal failure on chronic haemodialysis who had (99m)Tc-sestamibi-negative HPT. METHODS: (11)C-methionine PET/CT was performed in 18 patients (11 women and 7 men, aged 42-79 years; mean age 57.8 years) on haemodialysis for renal failure (2-14 years' duration), with normo-, hypo- or hypercalcaemia and HPT not localised by either dual-tracer (99m)Tc-pertechnetate/(99m)Tc-sestamibi subtraction scans or dual-phase (99m)Tc-sestamibi scans. RESULTS: In three of ten patients with normo- or hypocalcaemic HPT there was increased (11)C-methionine accumulation in one gland. Seven of eight patients with hypercalcaemic HPT showed increased uptake: in five of these patients increased (11)C-methionine accumulation was present in one gland, while in two it was demonstrated in two glands. All patients also had high-resolution ultrasound of the neck and were treated with subtotal parathyroidectomy, leaving a remnant of the smallest of the four glands. Regardless of their size, all glands with abnormal (11)C-methionine parathyroid uptake were removed, and all demonstrated parathyroid hyperplasia. All patients developed post-parathyroidectomy hypoparathyroidism and one patient with normocalcaemic HPT relapsed 8 months after surgery. CONCLUSION: These data suggest that (11)C-methionine PET/CT may be used to identify hyperfunctioning parathyroid glands in non-primary HPT, and especially hypercalcaemic HPT, when conventional (99m)Tc-sestamibi imaging is non-localising.

Detection and localization of prostate cancer: correlation of (11)C-choline PET/CT with histopathologic step-section analysis.

UNLABELLED: This study evaluated the potential usefulness of (11)C-choline PET/CT for detection and localization of tumors within the prostate. We used the results of step-section histopathologic examination as the standard of reference. METHODS: The results were analyzed on a sextant basis. We reviewed the results of the (11)C-choline PET/CT scans of 36 patients with prostate cancer and of 5 control subjects with bladder cancer. All patients underwent (11)C-choline PET/CT and, subsequently, radical prostatectomy with lymph node dissection within 1 mo. (11)C-Choline PET/CT scans were obtained 5-10 min after intravenous injection of 370-555 MBq of (11)C-choline. Images were reviewed visually and semiquantitatively using maximum SUV and tumor-to-background ratio. RESULTS: On a sextant basis, histopathologic analysis detected cancer foci in 143 of 216 sextants; high-grade prostate intraepithelial neoplasm foci were detected in 89 of 216 sextants (in 59 sextants in association with carcinoma, in 30 sextants alone), acute prostatitis was detected in 7 of 216 sextants (in 3 sextants in association with carcinoma, in 4 sextants alone), and 39 of 216 sextants were normal. PET/CT demonstrated focal (11)C-choline uptake in 108 sextants (94 of which involved tumor), and 108 sextants showed no abnormal (11)C-choline uptake (49 of which were false negative). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT were 66%, 81%, 71%, 87%, and 55%, respectively. In the 5 control subjects, high-grade prostate intraepithelial neoplasm was detected at histologic examination in 16 of 30 sextants. PET/CT showed increased (11)C-choline uptake in 5 of 16 sextants. CONCLUSION: This study demonstrated the feasibility of using (11)C-choline PET/CT to identify cancer foci within the prostate. However, we also found that (11)C-choline PET/CT has a relative high rate of false-negative results on a sextant basis and that prostatic disorders other than cancer may accumulate (11)C-choline. Therefore, our data do not support the routine use of PET/CT with (11)C-choline as a first-line screening procedure for prostate cancer in men at high risk.