Elena Incerti

Imaging biomarkers in prostate cancer: role of PET/CT and MRI

Prostate-specific antigen (PSA) is currently the most widely used biomarker of prostate cancer (PCa). PSA suggests the presence of primary tumour and disease relapse after treatment, but it is not able to provide a clear distinction between locoregional and distant disease. Molecular and functional imaging, that are able to provide a detailed and comprehensive overview of PCa extension, are more reliable tools for primary tumour detection and disease extension assessment both in staging and restaging. In the present review we evaluate the role of PET/CT and MRI in the diagnosis, staging and restaging of PCa, and the use of these imaging modalities in prognosis, treatment planning and response assessment. Innovative imaging strategies including new radiotracers and hybrid scanners such as PET/MRI are also discussed.

Radiation Treatment of Lymph Node Recurrence from Prostate Cancer: Is 11C-Choline PET/CT Predictive of Survival Outcomes?

PET/CT is a valuable tool to detect lymph node (LN) metastases in patients with biochemical failure after primary treatment for prostate cancer (PCa). The aim was to assess the predictive role of imaging parameters derived by 11C-choline PET/CT on survival outcomes—overall survival, locoregional relapse-free survival, clinical relapse-free survival (cRFS), and biochemical relapse-free survival (bRFS)—in patients treated with helical tomotherapy (HTT) for LN recurrence. Methods: This retrospective study included 68 patients affected by PCa (mean age, 68 y; age range, 51–81 y) with biochemical recurrence after primary treatment (median prostate-specific antigen values obtained at the time of PET/CT scan, 2.42 ng/mL; range, 0.61–27.56 ng/mL) who underwent 11C-choline PET/CT from January 2005 to January 2013 and were treated with HTT in correspondence of the pathologic choline LN uptake. PET-derived parameters, including maximum/mean standardized uptake value (SUVmax and SUVmean, respectively) and metabolic tumor volume (MTV) with a threshold of 40%, 50%, and 60% were calculated. The best cutoff values of PET-derived parameters discriminating between patients with and without relapse, after treatment guided by PET, were assessed by receiver-operating-characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analysis including the most predictive PET-derived parameters and survival outcomes were performed. Results: The median follow-up was 20 mo (mean, 26 mo; range, 3–97 mo). 11C-choline PET/CT showed pathologic LN uptake in 4 patients at the pelvic level, in 5 at the abdominal level, in 13 at both the pelvic and the abdominal level, and in 46 at the abdominal or pelvic or other sites. The 2-y overall survival, locoregional relapse-free survival, cRFS, and bRFS were 87%, 91%, 51%, and 40%, respectively. On the basis of ROC curves, the most discriminative cutoff value for MTV values was an MTV threshold of 60% (MTV60) of greater than 0.64 cm3. No significant cutoff values were found for SUVmax or SUVmean at univariate analysis, whereas MTV60 was confirmed as an independent predictor in multivariate analysis and significantly correlated with bRFS and cRFS. MTV60 and extrapelvic disease well predict the risk of cRFS. Conclusion: 11C-choline PET/CT performed as a guide for HTT on LN recurrence is predictive of survival. In particular, MTV60 and extrapelvic disease were the best predictors of tumor response for bRFS and cRFS in PCa patients with LN recurrence after primary treatment. This information may be useful in emerging treatment strategies.

Toxicity and efficacy of salvage carbon 11‐choline positron emission tomography/computed tomography‐guided radiation therapy in patients with lymph node recurrence of prostate cancer

To report the 3‐year toxicity and outcomes of carbon 11 (11C)‐choline‐positron emission tomography (PET)/computed tomography (CT)‐guided radiotherapy (RT), delivered via helical tomotherapy (HTT; Tomotherapy® Hi‐Art II® Treatment System, Accuray Inc., Sunnyvale, CA, USA) after lymph node (LN) relapses in patients with prostate cancer.

Evaluation of prostate cancer with 11C-Choline PET/CT for treatment planning, response assessment, and prognosis

The aim of this review is to report on the value of 11C-choline PET imaging as a diagnostic procedure for metastasis-directed therapies. Furthermore, the role of 11C-choline PET/CT as a diagnostic tool for monitoring castration-resistant prostate cancer patients treated with systematic therapy is assessed. Finally, the role of 11C-choline PET/CT in the prediction of survival in both castration-resistant prostate cancer patients and hormone-naïve patients is investigated.

First evaluation of PET based human biodistribution and dosimetry of 18F-FAZA, a tracer for imaging tumor hypoxia

18F-labeled fluoroazomycinarabinoside (18F-FAZA) is a PET biomarker for noninvasive identification of regional tumor hypoxia. The aim of the present phase I study was to evaluate the biodistribution and dosimetry of 18F-FAZA in non–small cell lung cancer patients. Methods: Five patients awaiting surgical resection of histologically proven or radiologically suspected non–small cell lung cancer were prospectively enrolled in the study. The patients underwent PET/CT after injection of 371 ± 32 MBq of 18F-FAZA. The protocol consisted of a 10-min dynamic acquisition of the heart to calculate the activity in blood, followed by 4 whole-body PET/CT scans, from the vertex to the mid thigh, at 10, 60, 120, and 240 min after injection. Urine samples were collected after each imaging session and at 360 min after injection. Volumes of interest were drawn around visually identifiable source organs to generate time–activity curves. Residence times were determined from time–activity curves, and effective doses to individual organs and the whole body were calculated using OLINDA/EXM 1.2 for the standard male and female phantoms. Results: Blood clearance was characterized by a rapid distribution followed by first-order elimination. The highest uptake was in muscle and liver, with respective percentage injected activity (%IA) peaks of 42.7 ± 5.3 %IA and 5.5 ± 0.6 %IA. The total urinary excretion was 15 %IA. The critical organ, with the highest absorbed radiation doses, was the urinary bladder wall, at 0.047 ± 0.008 and 0.067 ± 0.007 mGy/MBq for the 2- and 4-h voiding intervals, respectively. The effective doses for the standard male and female phantoms were 0.013 ± 0.004 and 0.014 ± 0.004 mSv/MBq, respectively, depending on the voiding schedule. Conclusion: With respect to the available literature, the biodistribution of 18F-FAZA in humans appeared to be slightly different from that in mice, with a low clearance in humans. Therefore, use of animal data may moderately underestimate radiation doses to organs in humans. Our dosimetry data showed that a 370-MBq injection of 18F-FAZA is safe for clinical use, similar to other widely used PET ligands. In particular, the effective dose is not appreciably different from those obtained with other hypoxia tracers, such as 18F-fluoromisonidazole.

11C- or 18F-Choline PET/CT for Imaging Evaluation of Biochemical Recurrence of Prostate Cancer

Recurrence of prostate cancer is suspected when an increase in the prostate-specific antigen level is detected after radical treatment; the recurrence could be local relapse, distant relapse, or both. Differentiation between the two patterns of relapse is critical for choosing the proper treatment strategy. Choline PET/CT could be of help in discriminating patients with local, lymph node, and bone recurrences, thus having an impact on patient management.

PET/MRI and prostate cancer

AbstractAdvances in medical imaging are needed to support the general goal of personalized patient-centric care. This is particularly true for prostate cancer, which frequently presents as the initial multifocal disease with variable significance and outcome, and, when aggressive, can recur after the initial definitive management. The combined simultaneous acquisition of multi-parametric magnetic resonance imaging and positron emission tomography (PET) can provide combined structural, metabolic, and functional imaging information regarding prostate cancer status in a whole-body single session examination. As described in this review article, combining PET and MRI appears particularly useful for pelvic disease assessments, as PET and MRI provide complementary information, which can be best obtained with hybrid PET/MR scanners. While there is growing interest in the field of prostate cancer imaging regarding the value of PET/MRI, the current literature in this field is sparse and insufficient for a systematic analysis. This article, therefore, highlights available evidence and future perspectives of PET/MRI for the initial diagnosis, staging, and restaging of prostate cancer with choline-based radiotracers as well as ligands to target prostate-specific membrane antigen.

Concomitant Lung Cancer and Gastrointestinal Stromal Tumor: First Report of Hypoxia Imaging With 18F-FAZA PET/CT

A 76-year-old man underwent F-FDG PET/CT to complete staging and characterize a suspicious lung mass. Images showed intense uptake in the lung lesion and faint uptake in correspondence of a gastric mass, which was subsequently biopsied revealing a gastrointestinal stromal tumor. A F-FAZA PET/CT was also performed because of patients enrollment in a prospective clinical trial (trial registration no. EudraCT 2011-002647-98), showing heterogeneous uptake of F-FAZA in the pulmonary lesion and faint uptake in correspondence of the gastrointestinal stromal tumor.

PET imaging for lymph node dissection in prostate cancer

The detection of neoplastic lymph nodal involvement in prostate cancer (PCa) patients has relevant therapeutic and prognostic significance, both in the clinical settings of primary staging and restaging. Lymph nodal dissection (LND) currently represents the gold standard for evaluating the presence of lymph nodal involvement. However, this procedure is invasive, associated with morbidity, and may fail in detecting all potential lymph nodal metastatic regions. Currently the criteria for lymph nodal detection using conventional imaging techniques mainly rely on morphological assessment with unsatisfactory diagnostic accuracy. Positron emission tomography (PET) represents a helpful imaging technique for a proper staging of lymph nodal status. The most investigated PET radiotracer is choline, although many others have been explored as guide for both primary and salvage LND, such as fluorodeoxyglucose, acetate, fluorocyclobutanecarboxylic acid and prostate-specific membrane antigen. In the present review, a comprehensive literature review addressing the role of PET for LND in PCa patients is reported, with the use of the above-mentioned radiotracers.

PET/MRI in gynecological tumors

The diagnostic approach to gynecological tumors includes anatomical and molecular imaging methods, representing a strong support for clinicians to define tumor extension, to plan the best treatment strategy and patient management. The possibility of combining morphological and functional information in a single examination, using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) technique, represents a very promising tool in the different settings of gynaecologic tumors. In the present review, the current literature and potential clinical applications of PET/MRI in the most common types of gynecological tumors are discussed. The role of PET/MRI is in staging, restaging and after treatment of gynecological tumors is presented, focusing on cervical, endometrial and ovarian cancer. Moreover, the diagnostic accuracy of PET/MRI and the correlation between quantitative parameters (standardized uptake value and apparent diffusion coefficient) of PET/MRI hybrid systems are briefly reviewed.