Impact of [64Cu][Cu(ATSM)] PET/CT in the evaluation of hypoxia in a patient with Glioblastoma: a case report.

BACKGROUND: Glioblastoma multiform (GBM), a malignant brain tumour, has a very often poor prognosis. The therapeutic approach is represented by surgery followed by radiotherapy and chemotherapy. Hypoxia is a factor that causes a reduction of both radiotherapy and chemotherapy effectiveness in GBM and other cancers. Through the use of [64Cu][Cu(ATSM)], a hypoxia-targeting positron emission tomography (PET) radiotracer, is possible to identify the presence of hypoxic areas within a lesion and therefore modulate the therapeutic approach according to the findings. CASE PRESENTATION: In this case report, we observed an increase of radiotracer uptake from early acquisition to late acquisition in hypoxia sites and high correlation between [64Cu][Cu(ATSM) PET/CT results and expression of the hypoxia marker HIF-1α. CONCLUSIONS: [64Cu][Cu(ATSM) PET/CT represents a valid opportunity to reveal in vivo hypoxic areas in GBM lesion which can guide clinicians on selecting GMB patient's therapeutic scheme.

Molecular imaging of brain tumors with radiolabeled choline PET.

Several positron emission tomography (PET) radiopharmaceuticals have been emerged in the last decade as feasible in the management of brain lesions, due to the low performance in this field of the 18F-fluoro-deoxyglucose (18F-FDG), for its high physiological gradient of distribution in the brain. Beyond its usefulness in prostate cancer imaging, the radiolabeled choline is becoming a promising tool in diagnosing benign and malignant lesions of the brain, due to a very low rate of distribution in normal white and grey matters. The aim of our review was to assess the real impact of the radiolabeled choline PET/CT in the management of brain benign lesions, brain tumors, and metastases. Furthermore, emphasis was given to the comparison between the radiolabeled choline and the other radiopharmaceuticals in this field. A literature review was performed. The radiolabeled choline is useful in the management of patients with suspected brain tumor relapse, especially in association with magnetic resonance imaging (MRI), with caution regarding its intrinsic characteristic of non-tumor-specific tracer. For the same reason, it is not useful in the early evaluation of brain lesions. Similar results are reported for other radiopharmaceuticals. The inclusion of the head in the whole-body scans for somatic tumors is necessary to ensure metastases in the brain or choline-avid benign lesions.

The SGK1 Kinase Inhibitor SI113 Sensitizes Theranostic Effects of the 64CuCl2 in Human Glioblastoma Multiforme Cells.

BACKGROUND/AIMS: The importance of copper in the metabolism of cancer cells has been widely studied in the last 20 years and a clear-cut association between copper levels and cancer deregulation has been established. Copper-64, emitting positrons and ß-radiations, is indicated for the labeling of a large number of molecules suitable for radionuclide imaging as well as radionuclide therapy. Glioblastoma multiforme (GBM) is the CNS tumor with the worse prognosis, characterized by high number of recurrences and strong resistance to chemo-radio therapy, strongly affecting patients survival. We have recently discovered and studied the small molecule SI113, as inhibitor of SGK1, a serine/threonine protein kinase, that affects several neoplastic phenotypes and signaling cascades. The SI113-dependent SGK1 inhibition induces cell death, blocks proliferation, perturbs cell cycle progression and restores chemo-radio sensibility by modulating SGK1-related substrates. In the present paper we aim to characterize the combined effects of 64CuCl2 and SI113 on human GBM cell lines with variable p53 expression. METHODS: Cell viability, cell death and stress/authopagic related pathways were then analyzed by FACS and WB-based assays, after exposure to SI113 and/or 64CuCl2. RESULTS: We demonstrate here, that i) 64CuCl2 is able to induce a time and dose dependent modulation of cell viability (with different IC50 values) in highly malignant gliomas and that the co-treatment with SI113 leads to ii) additive/synergistic effects in terms of cell death; iii) enhancement of the effects of ionizing radiations, probably by a TRC1 modulation; iv) modulation of the autophagic response. CONCLUSIONS: Evidence reported here underlines the therapeutic potential of the combined treatment with SI113 and 64CuCl2 in GBM cells.

Current status and future challenges of brain imaging with (18)F-DOPA PET for movement disorders.

OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disorder (ND) due to progressive loss of dopaminergic neurons in the basal ganglia. The correct differential diagnosis of this disease with parkinsonian syndromes (PS) or with essential tremor (ET) is a diagnostic dilemma, considering that only PD is responsive to treatment with levodopa. Traditional imaging fails to diagnose PD because morphological alterations in the brain are usually detectable only at advanced stages. Single photon emission tomography (SPET) with cocaine analogues has recently been used in the early detection of PD. The fluoro-18-deoxyphenyl-alanine ((18)F-DOPA) is a positron emission tomography (PET) tracer with selective in vivo affinity to the basal ganglia, due to the specific metabolism of substantia nigra. We assessed the effective use of (18)F-DOPA PET in brain imaging in order to describe the function of presynaptic disorders of PD, PS, ET and other movement disorders compared to SPET imaging and also discussed novel radiopharmaceuticals. The role of magnetic resonance imaging (MRI) was also discussed. CONCLUSION: (18)F-DOPA PET imaging is still the best diagnostic tool for the diagnosis of PD and other movement disorders. Fluorine-18-FDG PET can play a role in the differential diagnosis between PD and other PS. The hybrid (18)F-DOPA PET/MRI seems to be able to play an important additional role in early diagnosis of the above syndromes.

Comparison Between 64Cu-PSMA-617 PET/CT and 18F-Choline PET/CT Imaging in Early Diagnosis of Prostate Cancer Biochemical Recurrence.

PURPOSE: To evaluate the diagnostic performance of 64Cu-PSMA-617 positron emission tomography (PET) with computed tomography (CT) for restaging prostate cancer after biochemical recurrence (BCR) and to compare it with 18F-choline PET/CT in a per-patient analysis. PATIENTS AND METHODS: An observational study was performed of 43 patients with BCR after laparoscopic radical prostatectomy who underwent 64Cu-PSMA-617 PET/CT and subsequently 18F-choline PET/CT for restaging. The detection rates (DR) of 64Cu-PSMA-617 PET/CT and of 18F-choline PET/CT were calculated by standardized maximum uptake value (SUVmax) at 4 hours and SUVmax at 1 hour as reference, respectively. Furthermore, univariate logistic regression analysis was carried out to identify independent predictive factors of positivity with 64Cu-PSMA-617 PET/CT. RESULTS: An overall positivity with 64Cu-PSMA-617 PET/CT was found in 32 patients (74.4%) versus 19 (44.2%) with 18F-choline PET/CT. Specifically, after stratifying for prostate-specific antigen (PSA) values, we found a good performance of 64Cu-PSMA-617 PET/CT at low PSA levels compared to 18F-choline PET/CT, with a DR of 57.1% versus 14.3% for PSA 0.2-0.5 ng/mL (P = .031), and of 60% versus 30% with PSA 0.5-1 ng/mL. At univariate binary logistic regression analysis, PSA level was the only independent predictor of 64Cu-PSMA-617 PET/CT positivity. No significant difference in terms of DR for both 64Cu-PSMA-617 PET/CT and 18F-choline PET/CT was found according to different Gleason score subgroups. CONCLUSION: In our study cohort, a better performance was observed for 64Cu-PSMA-617 PET/CT compared to 18F-choline PET/CT in restaging after BCR, especially in patients with low PSA values.

11C-Choline PET/CT based Helical Tomotherapy as Treatment Approach for Bone Metastases in Recurrent Prostate Cancer Patients.

BACKGROUND: To evaluate the efficacy of 11C-choline PET/CT (CHO-PET/CT) based helical tomotherapy (HTT) as a therapeutic approach for bone metastases in recurrent prostate cancer (PCa) patients. METHODS: This retrospective study includes 20 PCa patients (median age: 67; range: 51-80 years) presenting biochemical relapse after primary treatment who underwent CHO-PET/CT based HTT on positive bone metastases from December 2007 to June 2014. The effectiveness of HTT has been assessed with biochemical response at 3/6/12 months, biochemical relapse free survival (bRFS) and overall survival (OS) at 2 years. Toxicity has also been considered and assessed according to Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: All patients presented a relapse at the time of CHO-PET/CT at bone level. In addition 15/20 (75%) also at lymph nodes (LNs) level (total lesions= 54). All patients underwent HTT on bone metastases and 19/20 concomitantly on prostatic bed and LNs. The median follow-up from CHO-PET/CT was 2 years (range: 1-7 years). At 3 months after the beginning of HTT treatment complete or partial biochemical response occurred in 79% of patients, at 6 months in 82% and at 12 months in 63% of patients. bRFS and OS at 2 years were 50% and 55% of patients, respectively. Patients presented mostly grade 1 or 2 toxicity according to CTCAE. The only grade 3 late toxicity has been observed in one patient. CONCLUSION: CHO-PET/CT based HTT is a suitable therapeutic approach in patients with recurrent PCa presenting bone metastases with a medium-low toxicity.

PET/CT with 18F-choline: Physiological whole bio-distribution in male and female subjects and diagnostic pitfalls on 1000 prostate cancer patients: 18F-choline PET/CT bio-distribution and pitfalls. A southern Italian experience.

INTRODUCTION: The 11C/18F-choline is a PET/CT radiopharmaceutical useful in detecting tumors with high lipogenesis. 11C/18F-choline uptake can occur in physiological conditions or tumors. The knowledge of its bio-distribution is essential to recognize physiologic variants or diagnostic pitfalls. Moreover, few information are available on the bio-distribution of this tracer in female patients. Our aim was to discuss some documented 18F-choline PET/CT pitfalls in prostate cancer patients. Our secondary aim was to describe the 18F-choline bio-distribution in the female body. METHODS: We collected diagnostic pitfalls in three PET centers examining 1000 prostate cancer by 18F-choline PET/CT. All pitfalls were ensured by follow-up, imaging and/or histology. We also performed whole body 18F-choline PET/CT in 5 female patients. RESULTS: 169/1000 (16.9%) patients showed pitfalls not owing to prostate cancer. These findings were due to inflammation, benign tumors while, in 1% of examined patients, a concomitant neoplasm was found. In the female body, the breast showed low physiological uptake. CONCLUSIONS: The accurate knowledge of 18F-choline PET/CT bio-distribution and diagnostic pitfalls is essential. Correlative imaging and histological exam are often necessary to depict pitfalls. In women, the uptake in the breast is due to the physiological gradient of 18F-choline uptake in the exocrine glands. ADVANCES IN KNOWLEDGE: Our results confirm the possibility of 18F-choline uptake in several diseases other than prostate cancer. However, our experience was acquired on a large population and shows that a conspicuous amount of 18F-choline diagnostic pitfalls are easily recognizable and attributable to inflammation. A new advance in knowledge is the minimal difference in terms of physiological tracer bio-distribution between male and female patients. IMPLICATIONS FOR PATIENT CARE: The knowledge of the physiological bio-distribution and of the potential pitfalls linked of a tracer could help physicians to choose the best diagnostic and therapeutic approaches for a better patient quality of life.

Diagnostic Accuracy of 64Copper Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Primary Lymph Node Staging of Intermediate- to High-risk Prostate Cancer: Our Preliminary Experience.

OBJECTIVE: To assess the diagnostic accuracy of 64Copper prostate-specific membrane antigen (64Cu-PSMA) positron emission tomography/computed tomography (PET/CT) in the primary lymph node (LN) staging of a selected cohort of intermediate- to high-risk prostate cancer (PCa) patients. MATERIALS AND METHODS: An observational prospective study was performed in 23 patients with intermediate- to high-risk PCa, who underwent 64Cu-PSMA PET/CT for local and lymph nodal staging before laparoscopic radical prostatectomy with an extended pelvic LN dissection. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for LN status of 64Cu-PSMA PET/CT were calculated using the final pathological findings as reference. Furthermore, we evaluated the correlation of intraprostatic tumor extent and grading with 64Cu-PSMA intraprostatic distribution. RESULTS: Pathological analysis of LN involvement in 413 LNs harvested from our study cohort identified a total of 22 LN metastases in 8 (5%) of the 23 (35%) PCa patients. Imaging-based LN staging in a per-patient analysis showed that 64Cu-PSMA PET/CT was positive in 7 of 8 LN-positive patients (22%) with a sensitivity of 87.5%, specificity of 100%, PPV of 100%, and NPV of 93.7%, considering the maximum standardized uptake value (SUVmax) at 4 hours as our reference. Receiver operating characteristic curve was characterized by an area under the curve of 0.938. A significant positive association was observed between SUVmax at 4 hours with Gleason score, index, and cumulative tumor volume. CONCLUSION: In our intermediate- to high-risk PCa patients study cohort, we showed the high diagnostic accuracy of 64Cu-PSMA PET/CT for primary LN staging before radical prostatectomy.