Cinzia Pettinato

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.

Early Biochemical Relapse After Radical Prostatectomy: Which Prostate Cancer Patients May Benefit from a Restaging 11C-Choline PET/CT Scan Before Salvage Radiation Therapy?

The aim of the study was to assess which factors may influence 11C-choline PET/CT detection rate in a population of recurrent prostate cancer (PCa) patients listed for salvage radiation therapy (S-RT) in an early phase of biochemical relapse, to select which patients could obtain the most benefit by performing restaging 11C-choline PET/CT before S-RT. Methods: The study comprised 605 patients, treated with radical prostatectomy (RP) with curative intent for PCa who showed rising PSA levels after primary therapy and listed for S-RT. Prostate-specific antigen (PSA) values were >0.2 ng/mL and <2 ng/mL (mean, 1.05 ng/mL; median, 1.07 ng/mL; range, 0.2–2 ng/m; SD, ±0.59). All patients were classified as N0 after RP. Seventeen of 605 patients received adjuvant RT together with RP, whereas 148 of 605 patients received androgen-deprivation therapy (ADT) at the time of PET/CT. PSA, PSA kinetics, Gleason score, age, time to biochemical relapse, ADT, and initial tumor stage were statistically analyzed to assess which factor could influence PET/CT positivity and the detection of local versus distant relapse. Results: 11C-choline PET/CT was positive in 28.4% of patients (172/605). Eighty-three of 605 patients were positive in the pelvis (group A), distant metastasis (group B) were detected in 72 of 605 patients, and local and distant sites of relapse were detected in 17 of 605 patients (group C). At multivariate analysis, PSA, PSA doubling time (PSAdt), and ongoing ADT were significant predictors for positive scan results, whereas PSA and PSAdt were significantly related to distant relapse detection (P < 0.05). At the receiver-operating-characteristic analysis, a PSA value of 1.05 ng/mL and PSAdt of 5.95 mo were determined to be the optimal cutoff values in the prediction of a positive 11C-choline PET/CT scan, with an area under the curve (AUC) of 0.625 for PSA and 0.677 for PSAdt. Conclusion: 11C-choline PET/CT may be suggested before S-RT during the early phase of biochemical relapse, to select patients who may benefit from this aggressive treatment. Particularly, patients showing fast PSA kinetics or PSA increasing levels despite ongoing ADT should be studied with 11C-choline PET/CT before S-RT, considering the higher probability to detect positive findings outside the pelvis.

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

BackgroundMultiple 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.AimAs 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.MethodsTen 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.ResultsFour 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).ConclusionAccording 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-FDG PET for Evaluating Malignant Pleural Mesothelioma

Malignant Pleural Mesothelioma (MPM) is a relatively rare neoplasia characterized by a poor prognosis. Recent studies show that new therapeutic approaches can lead to an improvement in life quality and to a prolonged survival; therefore, proper evaluation of MPM before, as well as after, therapy, is needed. The aim of this study was to evaluate the impact of 18F-FDG photon emission tomography (PET) scan compared to computed tomography (CT) findings in patients affected by MPM, whether untreated or already treated. We studied 15 consecutive patients (13 male and 2 female) with a histological diagnosis of MPM, with a mean age of 69.9 years (range: 38-78 years old) and a recent total-body CT scan. Five (5) patients were studied for staging, while 10 patients were studied after therapy. An FDG PET scan was carried out 60 minutes after an intravenous (i.v.) injection of 370 MBq of 18F-FDG. For each patient, we compared the PET stage to the CT stage, and evaluated the role of PET in choosing a therapeutic approach. In 9 of 15 (60%) patients, there was no difference between the PET and the CT stage. In 2 of 15 (13%) patients, PET upstaged the disease, while in 4 of 15 (27%) patients PET downstaged MPM. According to these results, patient management was changed in 3 cases. Specifically, 1 patient was excluded from surgery, and 2 patients had different chemotherapy. These data suggest that PET is useful in the evaluation of MPM, giving additional data that can clarify doubtful CT findings, especially regarding lymph node involvement and distant lesions. In conclusion, FDG PET was found to play a worth-while role in patient management.

Dopamine transporter gene polymorphism, SPECT imaging, and levodopa response in patients with Parkinson disease

Objectives:To assess the potential association between dopamine transporter (DAT) genotype, single photon emission CT (SPECT) measures using [123I]-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([123I]-FP-CIT) of striatal dopaminergic function, and oral levodopa response pattern in a cohort of patients with Parkinson disease. Methods:Thirty-six patients at different disease stages enrolled in the study. Each patient was examined by [123I]-FP-CIT SPECT and a standardized oral levodopa test on 2 separate days in a randomized order within 3 weeks. The main outcome variables were the specific-to-nonspecific tracer uptake ratio in the contralateral putamen for SPECT analysis; latency, duration, and magnitude of the motor effect; and presence of dyskinesias for the levodopa test. The variable number of tandem repeat (VNTR) polymorphisms of the gene coding for DAT were detected for each patient by standard methods. Results:Contralateral putamen [123I]-FP-CIT uptake ratios were similar in the patients carrying the 9-copy allele (n = 20) of the DAT VNTR compared with 10-repeat homozygotes (n = 16). No significant difference was found in levodopa main outcome variables and dyskinesia incidence between the two groups of patients stratified by DAT VNTR polymorphism. Conclusions:The study did not identify clinically relevant in vivo DAT neurochemical function phenotypes or levodopa response patterns associated with the DAT polymorphism.

Retro-orbital injection is an effective route for radiopharmaceutical administration in mice during small-animal PET studies.

Background and aimSmall-animal PET is acquiring importance for pre-clinical studies. In rodents, radiotracers are usually administrated via the tail vein. This procedure can be very difficult and time-consuming as soft tissue extravasations are very frequent and tail scars can prevent repeated injections after initial failure. The aim of our study was to compare the retro-orbital (RO) versus tail vein intravenous (i.v.) administration of 18F-FDG and 11C-choline in mice for small-animal PET studies. MethodsWe evaluated four healthy female ICR CD1 mice according to the following protocol. Day 1: each animal underwent an i.v. injection of 28 MBq of 11C-choline. PET scan was performed after 10 min and 40 min. Day 2: each animal received an RO injection of 28 MBq of 11C-choline. A PET scan was performed after 10 min and 40 min. Day 3: each animal received an i.v. injection of 28 MBq of 18F-FDG. A PET scan was performed after 60 min and 120 min. Day 4: each animal received an RO injection of 28 MBq of 18F-FDG. A PET scan was performed after 60 min and 120 min. Administration and image acquisition were performed under gas anaesthesia. For FDG studies the animals fasted for 2 h and were kept asleep for 20–30 min after injection, to avoid muscular uptake. Images were reconstructed with 2-D OSEM. For each scan ROIs were drawn on liver, kidneys, lung, brain, heart brown fat and muscles, and the SUV was calculated. We finally compared choline i.v. standard acquisition to choline RO standard acquisition; choline i.v. delayed acquisition to choline RO delayed acquisition; FDG i.v. standard acquisition to FDG RO standard acquisition; FDG i.v. delayed acquisition to FDG RO delayed acquisition. ResultsThe RO injections for both 18F-FDG and 11C-choline were comparable to the intravenous injection of 18F-FDG for the standard and delayed acquisitions. ConclusionThe RO administration in mice represents a technical advantage over intravenous administration in being an easier and faster procedure. However, its use requires high specific activity while its value in peptides and other receptor-specific radiopharmaceuticals needs further assessment.

Radioembolization with Yttrium-90 microspheres in hepatocellular carcinoma: Role and perspectives

Transarterial radioembolization (TARE) is a form of brachytherapy in which intra-arterially injected yttrium-90-loaded microspheres serve as a source for internal radiation purposes. On the average, it produces disease control rates exceeding 80% and it is a consolidated therapy for hepatocellular carcinoma (HCC); however, current data are all based on retrospective series or non-controlled prospective studies since randomized controlled trials comparing it with the other liver-directed therapies for intermediate and locally advanced stage HCC are still underway. The data available show that TARE provides similar or even better survival rates when compared to transarterial chemoembolization (TACE). First-line TARE is best indicated for both intermediate-stage patients (staged according to the barcelona clinic liver cancer staging classification) who have lesions which respond poorly to TACE due to multiple tumors or a large tumor burden, and for locally advanced-stage patients with solitary tumors, and segmental or lobar portal vein tumor thrombosis. In addition, emerging data have suggested the use of TARE in patients who are classified slightly beyond the Milan criteria regarding radical treatment for downstaging purposes. As a second-line treatment, TARE can also be applied in patients progressing to TACE or sorafenib; a large number of phase II/III trials are ongoing with the purpose of evaluating the best association with systemic therapies. Transarterial radioembolization is very well tolerated and has a low rate of complications which are mainly related to unintended non-target tissue irradiation, including the surrounding liver parenchyma. The complications can be additionally reduced by accurate patient selection and a strict pre-treatment evaluation including dosimetry and assessment of the vascular anatomy. Since a correct treatment algorithm for potential TARE candidates is not clear and standardized, this comprehensive review analyzes the best selection criteria for patients who really benefit from TARE and also the new advances of this therapy, which can be a very important weapon against HCC.

18F-Fluciclovine PET/CT for the Detection of Prostate Cancer Relapse: A Comparison to 11C-Choline PET/CT.

Purpose In recent years, a new PET compound (anti-3-18F-FACBC or 18F-fluciclovine) was tested for the detection of prostate cancer relapse. Despite very promising results, only preliminary data were available with regard to the comparison to 11C-choline. The aim of this study was to compare the detection rate of 18F-FACBC and 11C-choline in patients presenting a biochemical relapse. Patients and Methods Fifty patients radically treated for prostate cancer and presenting with rising prostate-specific antigen (PSA) levels were consecutively and prospectively enrolled. All the patients were out of hormonal therapy and underwent both 11C-choline PET/CT and 18F-fluciclovine PET/CT within 1 week. The results were compared in terms of detection rate on a patient and lesion basis. Furthermore, a more detailed analysis regarding local, lymph node, and bone relapse was performed. Results On a patient-based analysis, 18F-fluciclovine detection turned out to be significantly superior to 11C-choline (P < 0.000001). This result was also true on lesion, lymph node, bone lesion, and local relapse analysis (P < 0.0001 in all the cases). There was no significant difference in terms of target to background of positive lesions between 11C-choline and 18F-fluciclovine. When the patients were divided into groups with different PSA levels, 18F-fluciclovine had a superior detection rate for low, intermediate, and high PSA levels. Conclusions In our experimental conditions, 18F-fluciclovine provided a statistically significant better performance in terms of lesion detection rate as compared with 11C-choline. However, more studies are required to evaluate the clinical significance of these results in terms of sensitivity, specificity, and accuracy.

Cerebral functions and metabolism after antegrade selective cerebral perfusion in aortic arch surgery.

OBJECTIVES Antegrade selective cerebral perfusion (ASCP) represents the best method of cerebral protection during surgery of the thoracic aorta. However, brain integrity and metabolism after antegrade cerebral perfusion have not yet been investigated. We assessed cerebral positron emission tomography (PET), diffusion-weighted imaging, proton magnetic resonance spectroscopy and cognitive functions in patients undergoing either ASCP or coronary artery bypass grafting (CABG) to elucidate whether cerebral perfusion was associated with postoperative neuronal alterations, metabolic deficit or cognitive decline. METHODS Seventeen patients undergoing aortic arch surgery using ASCP with moderate hypothermia (26 degrees C) (ASCP group) and 15 patients undergoing elective on-pump CABG (CABG group) were prospectively enrolled in the study. Brain PET, diffusion-weighted imaging, proton magnetic resonance spectroscopy and neuropsychometric testing were performed preoperatively, and at 1 week and 6 months postoperatively (T1, T2 and T3, respectively). Patient data were compared for statistic analysis with a normal database made up of healthy subjects. RESULTS One patient in each group was excluded because they refused postoperative evaluation. There were neither strokes nor hospital deaths. Two patients suffered from temporary neurological dysfunction (one in each group). Proton magnetic resonance spectroscopy did not reveal significant alterations in cortical N-acetyl-aspartate (NAA) content within and between the groups at T2 and T3. In the ASCP group, brain diffusion-weighted magnetic resonance showed a significant increase of the apparent diffusion coefficient values, reflecting vasogenic cerebral oedema, at T2, that disappeared at T3. Magnetic resonance detected new focal brain lesions in two CABG group patients. In seven ASCP group patients, PET scan showed glucose hypometabolism in the occipital lobes at T2, which disappeared in five patients at successive examination (T3). Significant cognitive decline was not observed in any patient. Test score changes between and within groups were not significant. CONCLUSIONS There was no evidence of ischaemic brain injury after ASCP even if some degree of reversible brain oedema secondary to cardiopulmonary bypass (CPB) was present. The cognitive outcomes in patients undergoing ASCP were comparable to patients undergoing coronary artery bypass. The lack of left subclavian artery perfusion during cerebral perfusion leads to temporary glucose hypometabolism in the occipital lobes without neuronal injury.

Defining the Diagnosis in Echocardiographically Suspected Senile Systemic Amyloidosis

Senile systemic amyloidosis (SSA) is a cardiomyopathy mainly affecting elderly men due to intramyocardial deposition of wild-type (nonmutant) transthyretin (TTR) ([1][1]). Since the heart is the only involved organ, SSA—which requires endomyocardial biopsy (EMB) for a definite diagnosis—is often