Giancarlo Montini

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.

Role of [18F]Fluorodeoxyglucose Positron Emission Tomography Scan in the Follow-Up of Lymphoma

PURPOSE In lymphoma, [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) is routinely used for initial staging, early evaluation of treatment response, and identification of disease relapse. However, there are no prospective studies investigating the value of serial FDG-PET over time in patients in complete remission. PATIENTS AND METHODS All patients with lymphoma who achieved the first complete remission were prospectively enrolled onto the study and scheduled for serial FDG-PET scans at 6, 12, 18, and 24 months; further scans were then carried out on an annual basis. Overall, the population included 421 patients (160 patients with Hodgkins lymphoma [HL], 183 patients with aggressive non-Hodgkins lymphoma [NHL], and 78 patients with indolent follicular NHL). All patients had a regular follow-up evaluation, including complete clinical and laboratory evaluation, and final assessment of any suspect FDG-PET findings using other imaging procedures (computed tomography [CT] scan) and/or biopsy and/or clinical evolution. FDG-PET findings were reported as positive for relapse, inconclusive (when equivocal), or negative for relapse. RESULTS PET enabled documentation of lymphoma relapse in 41 cases at 6 months, in 30 cases at 12 months, in 26 cases at 18 months, in 10 cases at 24 months, and in 11 cases at more than 36 months. All 36 patients with inconclusive positive PET underwent biopsy; only 12 (33%) of 36 patients had a concomitant suggestion of positivity on CT. A lymphoma relapse was diagnosed in 24 (66%) of 36 patients. CONCLUSION Our results confirm FDG-PET as a valid tool for follow-up of patients with HL and NHL. In patients with inconclusive positive results, histologic confirmation plays an important role in identifying true relapse.

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.

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

PurposeTo 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 methodsFrom 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 · kg−1 18F-dopa intravenously, and imaged 60 min later using a hybrid PET/CT scanner. Results18F-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%). ConclusionsOur 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.

A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by 90Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma

BACKGROUND A prospective, single-arm, open-label, multicenter, nonrandomised phase II trial to evaluate efficacy and safety of short fludarabine, mitoxantrone, and rituximab (FMR) induction followed by radioimmunotherapy, in untreated, intermediate/high-risk follicular non-Hodgkins lymphoma (NHL) patients. PATIENTS AND METHODS Fifty-five patients were treated using a sequential treatment schedule of four induction cycles of FMR chemoimmunotherapy, and a subsequent consolidating single administration of (90)Y-ibritumomab tiuxetan ((90)Y-IT), 8-14 weeks later. Patients were eligible for radioimmunotherapy if at least in partial response (PR) after induction, with normal platelet and granulocyte counts and a bone marrow infiltration ≤ 25%. Primary study end points were response rate and hematologic toxic effects; secondary end points were overall survival (OS) and progression-free survival (PFS). RESULTS All the 55 patients received four induction cycles with an overall response rate of 96% (38 complete responses [CR] and 15 PR). Fifty-one patients (38 in CR and 13 in PR) received (90)Y-IT. By the end of the treatment, 49/55 patients achieved a CR. With a median follow-up of 21 months, the estimated 3-year PFS was 81% and the 3-year OS 100%. CONCLUSIONS This study has established feasibility, tolerability, and efficacy of a regimen composed by short FMR induction with (90)Y-IT consolidation in untreated intermediate/high-risk follicular NHL patients.

Radiation emission dose from patients administered 90Y-labelled radiopharmaceuticals: comparison of experimental measurements versus Monte Carlo simulation.

AimTo estimate the radiation dose delivered from patients injected with yttrium-90 (90Y)-labelled tiuxetan (Zevalin) to parents and the general population, comparing different techniques. MethodsThe radiation dose delivered from a group of eight patients injected with 90Y-Zevalin to treat recurrent lymphoma was measured. The data obtained with the Monte Carlo simulation test were compared with the experimental measurements obtained with an ionization chamber detector and with a crystal NaI(Tl) detector. ResultsA good correlation was found between the Monte Carlo simulation test and the ionization chamber detector results: the air kerma dose rate was 4.2±0.1 and 4.4±0.8 μGy/h, respectively (r=0.9, P<0.01). Moreover, more than 99.7% of the air kerma dose rate measured with the ionization chamber detector was because of the contribution of electrons, whereas the contribution of photons was less than 0.3%. In contrast, the air kerma dose rate measured with the crystal NaI(Tl) detector was significantly lower (0.76+0.12 μGy/h) in comparison with the Monte Carlo simulation test. This underestimation was related to the limited crystal NaI(Tl) detector response to low energy rates at variance with the ionization chamber detector. The effective radiation dose released by patients treated with 90Y-labelled tiuxetan to parents and the general population was approximately 0.1 mSv per treatment cycle. ConclusionUsing the Monte Carlo model as a benchmark to compare the experimental measurements obtained by the two different detectors, we found that the ionizing chamber detector was more accurate than the crystal Na(Tl) detector for measuring the exposure radiation dose delivered from patients administered with 90Y-labelled radiopharmaceuticals. Moreover, the effective radiation dose released by these patients to their parents and the general population is significantly lower than the value recommended by international reports and regulations.

C-Methionine PET/CT in Central Nervous System Tumours: A Review

Central nervous system (CNS) malignant tumors are usually treated with different combinations of surgery, radiotherapy and chemotherapy to achieve a radical treatment. After therapy, conventional imaging procedures (CT and MR) are useful to detect disease relapse but a correct differential diagnosis in presence post-surgical fibrosis, radionecrosis or oedema (benign conditions) may sometime be difficult. CNS shows physiologically an intense uptake of FDG and consequently, small and/or hypo/isometabolic malignant lesions are very difficult to detect, as they may be masked by the hypermetabolic surrounding tissue. 11C-Methionine is a radiolabeled aminoacid that physiologically do not accumulate into the brain, nor in case of benign conditions such as fibrosis, necrosis or oedema. On the other side, malignant lesions (although low grade) present an increased 11C-Methionine uptake due to an increased proteic metabolism and vascular permeability. Therefore 11CMethionine has optimal tumor-to-background ratio, making this radiotracer very useful to study CNS malignant tumors. The most appropriate indication for 11C-Methionine PET is the presence of non conclusive conventional imaging procedures, not allowing to discriminate between benign conditions and disease relapse. Other applications of 11C-Methionine PET are the definition of the radiotherapy field, the localization of the most metabolic area inside a mass to guide the biopsy and the early evaluation of radiotherapy effect, but all these applications are marginal and not yet validated.

PET/CT in Neuroendocrine Tumors

Neuroendocrine tumors (NETs) are a rare group of neoplasms that originate from pluripotent stem cells or differentiated neuroendocrine cells, mostly localized in the bronchus, lungs, or gastroenteropancreatic tract. This issue reviews the results achieved with PET. The potential applications of the most commonly used receptor or metabolic positron-emitter radiopharmaceuticals in the field of NET to stage or restage disease, to detect unknown primary tumor, and to assess and monitor therapy response to different kind of treatments are analyzed.

Somatostatin Receptor PET-CT

Somatostatin receptor PET-CThemploys positron emitting tracers (68Ga-DOTA-peptides) that specifically bind to somatostatin receptors (ssr) expressed on tumor cell surface and has been used mainly for the assessment of neuroendocrine tumors (NETs). NETs derive from neuroendocrine cells widely dispersed in the human body and present an increased expression of ssr, particularly of ssr2. 68Ga-DOTA-peptides are very accurate for the assessment of well-differentiated NETs, since being slow-growing tumors, they are not clearly visualized on 18F-FDG PET-CT scans.