Marina Hodolic

Gleason Score at Diagnosis Predicts the Rate of Detection of 18F-Choline PET/CT Performed When Biochemical Evidence Indicates Recurrence of Prostate Cancer: Experience with 1,000 Patients

The objective of this study was to explore the ability of the initial Gleason score (GS) to predict the rate of detection of recurrent prostate cancer (PCa) with 18F-choline PET/CT in a large cohort of patients. Methods: Data from 1,000 patients who had undergone 18F-choline PET/CT because of biochemical evidence of relapse of PCa between 2004 and 2013 were retrieved from databases at 4 centers. Continuous data were compared by the Student t test or ANOVA, and categoric variables were compared by the χ2 test. Univariable and multivariable analyses were performed by logistic regression. Results: The GS at diagnosis was less than or equal to 6 in 257 patients, 7 in 347 patients, and greater than 7 in 396 patients. The results of 645 PET/CT scans were positive for PCa recurrence. Eighty-one percent of the positive PET/CT results were found in patients with a PSA level of greater than or equal to 2 ng/mL, 43% were found in patients with a PSA level of 1–2 ng/mL, and 31% were found in patients with a PSA level of less than or equal to 1 ng/mL; 78.8% of patients with positive PET/CT results had a GS of greater than 7. The results of 18F-choline PET/CT scans were negative in 300 patients; 44% had a GS of less than or equal to 6, 35% had a GS of 7, and 17% had a GS of greater than 7. PET/CT results were rated as doubtful in only 5.5% of patients (median PSA, 1.8 ng/mL). When the GS was greater than 7, the rates of detection of 18F-choline PET/CT were 51%, 65%, and 91% for a PSA level of less than 1 ng/mL, 1–2 ng/mL, and greater than 2 ng/mL, respectively. In univariable and multivariable analyses, both a GS of 7 and a GS of greater than 7 were independent predictors for positive 18F-choline PET/CT results (odds ratios, 0.226 and 0.330, respectively; P values for both, <0.001). Conclusion: A high GS at diagnosis is a strong predictive factor for positive 18F-choline PET/CT scan results for recurrent PCa, even when the PSA level is low (i.e., ≤1 ng/mL).

Consequence of the introduction of routine FCH PET/CT imaging for patients with prostate cancer: a dual centre survey

Abstract Background. Fluorocholine(18F) (FCH) was introduced at the beginning of April 2010 in France, Slovenia and three other EU member states for the localisation of bone metastases of prostate cancer with PET. The aim of the study was to compare the evolution of diagnostic imaging in patients with prostate cancer using a new radiopharmaceutical FCH, observed in France and in Slovenia, and to quantify the consequence of the results of new imaging modality on the detection rate of abnormal metastases and recurrences of prostate cancer. Patients and methods. In two centres (France/Slovenia), a survey of the number of nuclear medicine examinations in patients with prostate cancer was performed, covering 5 quarters of the year since the introduction of FCH. For each examination, the clinical and biological circumstances were recorded, as well as the detection of bone or soft tissue foci. Results. Six hundred and eighty-eight nuclear medicine examinations were performed impatients with prostate cancer. Nuclear medicine examinations were performed for therapy monitoring and follow-up in 23% of cases. The number of FCH PET/CT grew rapidly between the 1st and 5th period of the observation (+220%), while the number of bone scintigraphies (BS) and fluoride(18F) PET/CTs decreased (-42% and -23% respectively). Fluorodeoxyglucose(18F) (FDG) PET/CT remained limited to few cases of castrate-resistant or metastatic prostate cancer in Paris. The proportion of negative results was significantly lower with FCH PET/CT (14%) than with BS (49%) or fluoride(18F) PET/CT (54%). For bone metastases, the detection rate was similar, but FCH PET/CT was performed on average at lower prostate-specific antigen (PSA) levels and was less frequently doubtful (4% vs. 28% for BS). FCH PET/CT also showed foci in prostatic bed (53% of cases) or in soft tissue (35% of cases). Conclusions. A rapid development of FCH PET/CT was observed in both centres and led to a higher detection rate of prostate cancer lesions.

Malignant disease as an incidental finding at ¹⁸F-FDG-PET/CT scanning in patients with granulomatous lung disease.

PurposeFluorine-18 fluorodeoxyglucose (18F-FDG)-PET/computed tomography (CT) is used for assessment of the extent and activity of disease in patients with inflammatory granulomatous lung disease, in particular sarcoidosis and tuberculosis. The aim of this retrospective analysis was to assess the value of 18F-FDG-PET/CT in the identification of previously unknown malignant disease during routine investigation of granulomatous lung disease. Materials and methodsFrom July 2008 to December 2013, a total of 122 patients with tuberculosis (76 male and 46 female patients; age range 19.6–88.6 years, mean 52.8±16.6 years) and 85 patients with sarcoidosis (46 male and 39 female patients; age range 17.8–76.5 years, mean 48.6±13.8 years) underwent 18F-FDG-PET/CT. Reports were generated in consensus by both a nuclear medicine physician and a radiologist. Possibly malignant findings underwent biopsies and/or follow-up. Quantitative parameters (maximum standardized uptake value) were pooled and compared from reference lesions in each group. ResultsMalignant disease was suspected in 18 of 122 tuberculosis patients and in eight of 85 sarcoidosis patients. Malignancy was finally confirmed in six patients with tuberculosis and in two patients with sarcoidosis. In one single case a malignant lung tumour had been overlooked on PET/CT. Patients were also analysed according to their age. In the patient group older than 60 years, four malignancies were confirmed in 44 tuberculosis patients and in one in 20 sarcoidosis patients, whereas in patients aged between 30 and 60 years only three of 63 tuberculosis and one of 58 sarcoidosis cases showed malignancy compared with the 18 false-positive findings on a total patient basis. The most common site of malignant disease was the chest. Besides the intrathoracic findings, two cases of malignancy were detected outside the thorax. Quantitative evaluation did not reveal any statistically significant difference between the tuberculosis and sarcoidosis groups. ConclusionDifferentiation between granulomatous inflammation and malignancy is challenging with 18F-FDG-PET/CT because of a large number of false-positive findings. The highest probability of detecting coexistent malignant disease was seen in patients older than 60 years who were suffering from tuberculosis. An important feature for identification of malignant disease, especially in the assessment of intrathoracic findings, has turned out to be the CT pattern; quantitative evaluation, in contrast, seems to have little clinical value.

Metastatic prostate cancer proven by 18F-FCH PET/CT staging scan in patient with normal PSA but high PSA doubling time.

A 59-year-old man presented with frequent urination. Six months ago, his prostate-specific antigen (PSA) was 1.56 ng/mL; currently it is 3.5 ng/mL (PSA doubling time = 6 months; PSA velocity = 0.19 ng/mL/mo). Biopsy revealed aggressive prostate cancer (Gleason score 5 + 5). Staging with (18)F-fluorocholine PET/CT ((18)F-FCH PET/CT) demonstrated lymph node metastasis. After 6 months of hormonal therapy with goserelin, PSA decreased to 0.38 ng/mL. A (18)F-FCH PET/CT restaging scan demonstrated a global reduction of (18)F-FCH lesion uptake with disappearance of some mediastinal and iliac pelvic lymph node activity.

18F-fluorodeoxyglucose and 18F-flumazenil positron emission tomography in patients with refractory epilepsy

Abstract Background Epilepsy is a neurological disorder characterized by epileptic seizures as a result of excessive neuronal activity in the brain. Approximately 65 million people worldwide suffer from epilepsy; 20–40% of them are refractory to medication therapy. Early detection of disease is crucial in the management of patients with epilepsy. Correct localization of the ictal onset zone is associated with a better surgical outcome. The modern non-invasive techniques used for structural-functional localization of the seizure focus includes electroencephalography (EEG) monitoring, magnetic resonance imaging (MRI), single photon emission tomography/computed tomography (SPECT/CT) and positron emission tomography/computed tomography (PET/CT). PET/CT can predict surgical outcome in patients with refractory epilepsy. The aim of the article is to review the current role of routinely used tracer 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) as well as non routinely used 18F-Flumazenil (18F-FMZ) tracers PET/CT in patients with refractory epilepsy. Conclusions Functional information delivered by PET and the morphologic information delivered by CT or MRI are essential in presurgical evaluation of epilepsy. Nowadays 18F-FDG PET/CT is a routinely performed imaging modality in localization of the ictal onset zone in patients with refractory epilepsy who are unresponsive to medication therapy. Unfortunately, 18F-FDG is not an ideal PET tracer regarding the management of patients with epilepsy: areas of glucose hypometabolism do not correlate precisely with the proven degree of change within hippocampal sclerosis, as observed by histopathology or MRI. Benzodiazepine-receptor imaging is a promising alternative in nuclear medicine imaging of epileptogenic focus. The use of 11C-FMZ in clinical practice has been limited by its short half-life and necessitating an on-site cyclotron for production. Therefore, 18F-FMZ might be established as one of the tracers of choice for patients with refractory epilepsy because of better sensitivity and anatomical resolution.

18F-FET and 18F-FCH uptake in human glioblastoma T98G cell lines

Abstract Background Despite complex treatment of surgery, radiotherapy and chemotherapy, high grade gliomas often recur. Differentiation between post-treatment changes and recurrence is difficult. 18F-methyl-choline (18F-FCH) is frequently used in staging and detection of recurrent prostate cancer disease as well as some brain tumours; however accumulation in inflammatory tissue limits its specificity. The 18F-ethyl-tyrosine (18F-FET) shows a specific uptake in malignant cells, resulting from increased expression of amino acid transporters or diffusing through the disrupted blood-brain barrier. 18F-FET exhibits lower uptake in machrophages and other inflammatory cells. Aim of this study was to evaluate 18F-FCH and 18F-FET uptake by human glioblastoma T98G cells. Material and methods Human glioblastoma T98G or human dermal fibroblasts cells, seeded at a density to obtain 2 × 105 cells per flask when radioactive tracers were administered, grew adherent to the plastic surface at 37°C in 5% CO2 in complete medium. Equimolar amounts of radiopharmaceuticals were added to cells for different incubation times (20 to 120 minutes) for 18F-FCH and 18F-FET respectively. The cellular radiotracer uptake was determined with a gamma counter. All experiments were carried out in duplicate and repeated three times. The uptake measurements are expressed as the percentage of the administered dose of tracer per 2 × 105 cells. Data (expressed as mean values of % uptake of radiopharmaceuticals) were compared using parametric or non-parametric tests as appropriate. Differences were regarded as statistically significant when p<0.05. Results A significant uptake of 18F-FCH was seen in T98G cells at 60, 90 and 120 minutes. The percentage uptake of 18F-FET in comparison to 18F-FCH was lower by a factor of more than 3, with different kinetic curves.18F-FET showed a more rapid initial uptake up to 40 minutes and 18F-FCH showed a progressive rise reaching a maximum after 90 minutes. Conclusions 18F-FCH and 18F-FET are candidates for neuro-oncological PET imaging. 18F-FET could be the most useful oncological PET marker in the presence of reparative changes after therapy, where the higher affinity of 18F-FCH to inflammatory cells makes it more difficult to discriminate between tumour persistence and non-neoplastic changes. Additional studies on the influence of inflammatory tissue and radionecrotic cellular components on radiopharmaceutical uptake are necessary.

Uptake of 18F-FET and 18F-FCH in Human Glioblastoma T98G Cell Line after Irradiation with Photons or Carbon Ions

The differential diagnosis between recurrence of gliomas or brain metastases and this phenomenon is important in order to choose the best therapy and predict the prognosis but is still a big problem for physicians. The new emerging MRI, CT, and PET diagnostic modalities still lack sufficient accuracy. Radiolabeled choline and amino acids have been reported to show great tumor specificity. We studied the uptake kinetics of [18F]fluoromethyl-choline (FCH) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) by the T98G human glioblastoma cells from 20 to 120 min after irradiation either with photons at 2-10-20 Gy or with carbon ions at 2 Gy (at the National Centre for Oncological Hadrontherapy (CNAO), Pavia, Italy). We also evaluated the cell death and morphology changes induced by radiation treatment. Both FET and FCH are able to trace tumor behavior in terms of higher uptake for increased doses of radiation treatment, due to the upregulation of cells attempts to repair nonlethal damage. Our data suggest that both FCH and FET could be useful to analyze the metabolic pathways of glioblastoma cells before and after radiotherapy. Physicians will have to consider the different kinetics pathways of uptake concerning the two radiopharmaceuticals.

Importance of Gleason score on 18F-choline PET/CT findings in patients with biochemical relapse of prostate cancer disease (PSA<1.0 ng/ml).

86 Background: Not all tumors show significant increase of metabolic activity on 18F-FDG PET/CT imaging. This is particularly true for prostate cancer, neuroendocrine tumors and hepatic tumors. As a component of cell membrane phospholipids, choline is an excellent biomarker for the malignant transformation and increased proliferation of cells. 18F-choline (18F-FCH) PET/CT is a nuclear medicine procedure that has greater sensitivity and accuracy than 18F-FDG PET/CT to detect prostate malignancy: sensitivity 73% vs. 31% and accuracy 67% vs. 53%, respectively. The efficiency of FCH to detect prostate cancer disease before and after treatment is related to the PSA levels. Evaluation of recurrent disease with 18F-FCH PET/CT imaging in patients with prostate cancer disease is becoming a routine procedure. PURPOSE To investigate the role of Gleason score (GS), as a marker of proliferation, on 18F-FCH PET/CT findings in patients with biochemical relapse of prostate cancer disease defined as increased level of prostate specific antigen (PSA). METHODS 140 patients with biochemical relapse (PSA<1.0 ng/ml) underwent 18F-FCH PET/CT scan after treatment: radical prostatectomy, radiotherapy, hormonal therapy alone or combined treatment. RESULTS 18F-FCH PET/CT detected prostate cancer recurrence in 97% of patients with GS>7, 82% of patients with GS=7 and 63% of patients with GS<7. All patients had PSA between 0.2 and 1.0 ng/ml. Out of 140 patients 43% had recurrence in prostatic bed and 57% patients had local metastasis. CONCLUSIONS Prostate cancer proliferation defined as Gleason score, influence 18F-FCH PET/CT findings in patients with biochemical relapse of prostate cancer disease at any PSA level.

SPECT/CT for tumour imaging

Somatostatine receptor scintigraphy (SRS) with somatostatine analogs is nowadays established as a first-line tool in the detection, staging and evaluation of the response of neuroendocrine tumors (NETs) and some neural crest tumors, yielding much better results than conventional imaging techniques [1] as many subtypes of these tumors overexpress a high density of somatostatine receptors at the cell surface [2, 3]. This overexpression of the somatostatin receptors, however, may also be present in some other tumors, such as differentiated thyroid carcinoma, lung cancer, breast cancer, meningiomas, well-differentiated astrocytomas, pituitary tumors, lymphoma and several others [4–7]. Some benign conditions, mainly related to the presence of inflammatory cells, i.e., in thyroidal oftalmopathy [8], may also show an increased expression of these surface receptors.