Treatment modalities and survival outcomes in prostate cancer parenchymal brain metastasis.

BACKGROUND: Prostate cancer (PCa) parenchymal brain metastases are uncommon and troubling observations in the course of the disease. Our study aims to evaluate the prevalence of brain metastases among PCa patients while reporting various therapeutic modalities, clinical features, and oncological outcomes. METHODS: We retrospectively identified 34 patients with parenchymal brain metastasis out of 4575 patients using a prospectively maintained database that contains clinicopathologic characteristics of PCa patients between January 2012 and December 2021. Based on the three treatment modalities used, the patients were divided into three groups: stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and systemic therapy alone. The Kaplan-Meier curve was used to calculate overall survival [OS] probability and the Cox proportional hazards regression model was used to compare between groups. RESULTS: At the time of brain metastasis diagnosis, the median age was 66 years, the median (interquartile range [IQR]) prostate-specific antigen (PSA) was 2.2 (0.1-26.6) ng/ml and the median (IQR) months from initial PCa diagnosis to brain metastasis development was 70.8 (27.6-100.9). The median (IQR) primary Gleason score was 8 (7-9) and over a median (IQR) follow-up time of 2.2 (1.2-16.5) months, 76.5% (n = 26) of the patients died. Thirteen (38.2%) patients had solitary lesion, whereas 21 (61.8%) had ≥2 lesions. The lesions were supratentorial in 19 (55.9%) patients, infratentorial in six (17.6%), and both sides in nine (26.5%). Among all 34 patients, 10 (29.4%) were treated with SRS, seven (20.6%) with WBRT, and 17 (50%) with systemic therapy alone. OS varied greatly between the three treatment modalities (log-rank test, p = 0.049). Those who were treated with SRS and WBRT had better OS compared with patients who were treated with systemic therapy alone (hazard ratio: 0.37, 95% confidence interval: 0.16-0.86, p = 0.022). CONCLUSIONS: In our single-institutional study, we confirmed that PCa brain metastasis is associated with poor survival outcomes and more advanced metastatic disease. Furthermore, we found that SRS and WBRT for brain metastasis in patients with recurrent PCa appear to be associated with improved OS as compared with systemic therapy alone and are likely secondary to selection bias.

Rationale and design of the RAPID-WATER-FLOW trial: Radiolabeled perfusion to identify coronary artery disease using water to evaluate responses of myocardial FLOW.

OBJECTIVES: The objective of this study was to determine the diagnostic performance of 15O-water positron emission tomography (PET) myocardial perfusion imaging to detect coronary artery disease (CAD) using the truth-standard of invasive coronary angiography (ICA) with fractional flow reserve (FFR) or instantaneous wave-Free Ratio (iFR) or coronary computed tomography angiogram (CCTA). BACKGROUND: 15O-water has a very high first-pass extraction that allows accurate quantification of myocardial blood flow and detection of flow-limiting CAD. However, the need for an on-site cyclotron and lack of automated production at the point of care and relatively complex image analysis protocol has limited its clinical use to date. METHODS: The RAPID WATER FLOW study is an open-label, multicenter, prospective investigation of the accuracy of 15O-water PET to detect obstructive angiographic and physiologically significant stenosis in patients with suspected CAD. The study will include the use of an automated system for producing, dosing, and injecting 15O-water and enrolling approximately 215 individuals with suspected CAD at approximately 10 study sites in North America and Europe. The primary endpoint of the study is the diagnostic sensitivity and specificity of the 15O-water PET study using the truth-standard of ICA with FFR or iFR to determine flow-limiting stenosis, or CCTA to rule out CAD and incorporating a quantitative analytic platform developed for the 15O-water PET acquisitions. Sensitivity and specificity are to be considered positive if the lower bound of the 95% confidence interval is superior to the threshold of 60% for both, consistent with prior registration studies. Subgroup analyses include assessments of diagnostic sensitivity, specificity, and accuracy in female, obese, and diabetic individuals, as well as in those with multivessel disease. All enrolled individuals will be followed for adverse and serious adverse events for up to 32 hours after the index PET scan. The study will have >90% power (one-sided test, α = 0.025) to test the hypothesis that sensitivity and specificity of 15O-water PET are both >60%. CONCLUSIONS: The RAPID WATER FLOW study is a prospective, multicenter study to determine the diagnostic sensitivity and specificity of 15O-water PET as compared to ICA with FFR/iFR or CCTA. This study will introduce several novel aspects to imaging registration studies, including a more relevant truth standard incorporating invasive physiologic indexes, coronary CTA to qualify normal individuals for eligibility, and a more quantitative approach to image analysis than has been done in prior pivotal studies. CLINICAL TRIAL REGISTRATION INFORMATION: Clinical-Trials.gov (#NCT05134012).

International EANM-SNMMI-ISMRM consensus recommendation for PET/MRI in oncology.

PREAMBLE: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The merged International Society for Magnetic Resonance in Medicine (ISMRM) is an international, nonprofit, scientific association whose purpose is to promote communication, research, development, and applications in the field of magnetic resonance in medicine and biology and other related topics and to develop and provide channels and facilities for continuing education in the field.The ISMRM was founded in 1994 through the merger of the Society of Magnetic Resonance in Medicine and the Society of Magnetic Resonance Imaging. SNMMI, ISMRM, and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine and/or magnetic resonance imaging. The SNMMI, ISMRM, and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and/or magnetic resonance imaging and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each practice guideline, representing a policy statement by the SNMMI/EANM/ISMRM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI, ISMRM, and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging and magnetic resonance imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized. These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI, the ISMRM, and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

Targeted Alpha-Particle Therapy: A Review of Current Trials.

Radiopharmaceuticals are rapidly developing as a field, with the successful use of targeted beta emitters in neuroendocrine tumors and prostate cancer serving as catalysts. Targeted alpha emitters are in current development for several potential oncologic indications. Herein, we review the three most prevalently studied conjugated/chelated alpha emitters (225actinium, 212lead, and 211astatine) and focus on contemporary clinical trials in an effort to more fully appreciate the breadth of the current evaluation. Phase I trials targeting multiple diseases are now underway, and at least one phase III trial (in selected neuroendocrine cancers) is currently in the initial stages of recruitment. Combination trials are now also emerging as alpha emitters are integrated with other therapies in an effort to create solutions for those with advanced cancers. Despite the promise of targeted alpha therapies, many challenges remain. These challenges include the development of reliable supply chains, the need for a better understanding of the relationships between administered dose and absorbed dose in both tissue and tumor and how that predicts outcomes, and the incomplete understanding of potential long-term deleterious effects of the alpha emitters. Progress on multiple fronts is necessary to bring the potential of targeted alpha therapies into the clinic.

Atypical Metastases in the Abdomen and Pelvis From Biochemically Recurrent Prostate Cancer: 11C-Choline PET/CT With Multimodality Correlation.

PET with targeted radiotracers has become integral to mapping the location and burden of recurrent disease in patients with biochemical recurrence (BCR) of prostate cancer (PCa). PET with 11C-choline is part of the National Comprehensive Cancer Network and European Association of Urology guidelines for evaluation of BCR. With advances in PET technology, increasing use of targeted radiotracers, and improved survival of patients with BCR because of novel therapeutics, atypical sites of metastases are being increasingly encountered, challenging the conventional view that prostate cancer rarely metastasizes beyond bones or lymph nodes. The purpose of this article is to describe such atypical metastases in the abdomen and pelvis on 11C-choline PET (including metastases to the liver, pancreas, genital tract, urinary tract, peritoneum, abdominal wall, and perineural spread) and to present multimodality imaging features and relevant imaging pitfalls. Given atypical metastases' inconsistent relationship with the serum PSA level and the nonspecific presenting symptoms, atypical metastases are often first detected on imaging. Awareness of their imaging features is important because their detection affects clinical management, patient counseling, prognosis, and clinical trial eligibility. Such awareness is particularly critical because the role of radiologists in the imaging and management of BCR will continue to increase given the expanding regulatory approvals of other targeted and theranostic radiotracers.

How We Do It: A Multidisciplinary Approach to 177Lu DOTATATE Peptide Receptor Radionuclide Therapy.

Lutetium 177 (177Lu) DOTA-0-Tyr3-Octreotate (DOTATATE) peptide receptor radionuclide therapy (PRRT) is an effective treatment for advanced gastroenteropancreatic neuroendocrine tumors. This review presents a clinical practice workflow that has been successful since 177Lu DOTATATE PRRT was approved by the U.S. Food and Drug Administration. The workflow relies heavily on the input of a multidisciplinary team and involves a nuclear medicine consultation service, tumor board, and specific preparations in advance of therapy and day-of-therapy procedures. A systematic checklist designed to ensure appropriate selection of treatment candidates and identification of any concerns to address to safely administer PRRT is provided. All patients were evaluated with gallium 68 DOTATATE PET/CT, and in cases of high-grade tumors, they were also evaluated with fluorine 18 fluorodeoxyglucose PET/CT, with imaging findings reviewed as part of the systematic checklist before PRRT. Adverse effects are discussed and imaging follow-up regimens are reviewed, including alternative diagnostic contrast materials. Approaches to multiple challenging patient scenarios are illustrated through case examples. Finally, alternative theranostic radionuclides and treatment strategies are discussed.

Novel imaging techniques using 18 F-florbetapir PET/MRI can guide fascicular nerve biopsy in amyloid multiple mononeuropathy.

BACKGROUND: Multiple mononeuropathy is a rare presentation of primary (AL) amyloidosis and nerve biopsy is usually needed for diagnosis. Conventional imaging is useful to identify proximal nerve involvement but may be inadequate. We report a patient with multiple mononeuropathy whose presentation was suggestive of AL amyloid neuropathy and in whom repeated tissue biopsies were negative for amyloid (including two sensory nerves and one muscle). METHODS: The patient underwent magnetic resonance imaging (MRI) and whole body 18 F-florbetapir positron emission tomography (PET)/MRI. RESULTS: Whole body 18 F-florbetapir PET/MRI revealed abnormal low-level florbetapir uptake in the right proximal tibial and peroneal nerves, which provided a target for a sciatic bifurcation fascicular nerve biopsy that was diagnostic of AL amyloidosis. CONCLUSIONS: 18 F-florbetapir PET/MRI imaging is a promising diagnostic tool for patients with suspected peripheral nerve amyloidosis (including multiple mononeuropathy) in whom conventional imaging and nerve and muscle biopsies miss the pathology.

Frequency and Characteristics of Nodal and Deltoid FDG and 11C-Choline Uptake on PET Performed After COVID-19 Vaccination.

BACKGROUND. COVID-19 vaccination may trigger reactive lymphadenopathy, confounding imaging interpretation. There has been limited systematic analysis of PET findings after COVID-19 vaccination. OBJECTIVE. The purpose of this study was to evaluate the frequency and characteristics of abnormal FDG and 11C-choline uptake on PET performed after COVID-19 vaccination. METHODS. This retrospective study included 67 patients (43 men and 24 women; mean [± SD] age, 75.6 ± 9.2 years) who underwent PET examination between December 14, 2020, and March 10, 2021, after COVID-19 vaccination and who had undergone prevaccination PET examination without visible axillary node uptake. A total of 52 patients received the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech; hereafter referred to as the Pfizer-BioNTech vaccine), and 15 received the SARS-CoV-2 mRNA-1273 vaccine (Moderna; hereafter referred to as the Moderna vaccine). Sixty-six of the patients underwent PET/CT, and one underwent PET/MRI. Fifty-four PET examinations used FDG, and 13 used 11C-choline. PET was performed a median of 13 and 10 days after vaccination for patients who had received one (n = 44) and two (n = 23) vaccine doses, respectively. Two nuclear medicine physicians independently reviewed images and were blinded to injection laterality and the number of days since vaccination. Lymph node or deltoid SUVmax greater than the blood pool SUVmax was considered positive. Interreader agreement was assessed, and the measurements made by the more experienced physician were used for subsequent analysis. RESULTS. Positive axillary lymph node uptake was observed in 10.4% (7/67) of patients (7.4% [4/54] of FDG examinations and 23.1% [3/13] of 11C-choline examinations); of the patients with positive axillary lymph nodes, four had received the Pfizer vaccine, and three had received the Moderna vaccine. Injection laterality was documented for five of seven patients with positive axillary lymph nodes and was ipsilateral to the positive node in all five patients. PET was performed within 24 days of vaccination for all patients with a positive node. One patient showed extraaxillary lymph node uptake (ipsilateral supraclavicular uptake on FDG PET). Ipsilateral deltoid uptake was present in 14.5% (8/55) of patients with documented injection laterality, including 42.9% (3/7) of patients with positive axillary lymph nodes. Interreader agreement for SUV measurements (expressed as intraclass correlation coefficients) ranged from 0.600 to 0.988. CONCLUSION. Increased axillary lymph node or ipsilateral deltoid uptake is occasionally observed on FDG or 11C-choline PET performed after COVID-19 vaccination with the Pfizer-BioNTech or Moderna vaccine. CLINICAL IMPACT. Interpreting physicians should recognize characteristics of abnormal uptake on PET after COVID-19 vaccination to guide optimal follow-up management and reduce unnecessary biopsies.

Borderline Resectable and Locally Advanced Pancreatic Cancer: FDG PET/MRI and CT Tumor Metrics for Assessment of Pathologic Response to Neoadjuvant Therapy and Prediction of Survival.

BACKGROUND. Imaging biomarkers of response to neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDA) are needed to optimize treatment decisions and long-term outcomes. OBJECTIVE. The purpose of this study was to investigate metrics from PET/MRI and CT to assess pathologic response of PDA to NAT and to predict overall survival (OS). METHODS. This retrospective study included 44 patients with 18F-FDG-avid borderline resectable or locally advanced PDA on pretreatment PET/MRI who also underwent post-NAT PET/MRI before surgery between August 2016 and February 2019. Carbohydrate antigen 19-9 (CA 19-9) level, metabolic metrics from PET/MRI, and morphologic metrics from CT (n = 34) were compared between pathologic responders (College of American Pathologists scores 0 and 1) and nonresponders (scores 2 and 3). AUCs were measured for metrics significantly associated with pathologic response. Relation to OS was evaluated with Cox proportional hazards models. RESULTS. Among 44 patients (22 men, 22 women; mean age, 62 ± 11.6 years), 19 (43%) were responders, and 25 (57%) were nonresponders. Median OS was 24 months (range, 6-42 months). Before treatment, responders and nonresponders did not differ in CA 19-9 level, metabolic metrics, or CT metrics (p > .05). After treatment, responders and nonresponders differed in complete metabolic response (CMR) (responders, 89% [17/19]; nonresponders, 40% [10/25]; p = .04], mean change in SUVmax (ΔSUVmax; responders, -70% ± 13%; nonresponders, -37% ± 42%; p < .001), mean change in SUVmax corrected to serum glucose level (ΔSUVgluc) (responders, -74% ± 12%; nonresponders, -30% ± 58%; p < .001), RECIST response on CT (responders, 93% [13/14]; nonresponders, 50% [10/20]; p = .02)], and mean change in tumor volume on CT (ΔTvol) (responders, -85% ± 21%; nonresponders, 57% ± 400%; p < .001). The AUC of CMR for pathologic response was 0.75; ΔSUVmax, 0.83; ΔSUVgluc, 0.87; RECIST, 0.71; and ΔTvol 0.86. The AUCs of bivariable PET/MRI and CT models were 0.83 (CMR and ΔSUVmax), 0.87 (CMR and ΔSUVgluc), and 0.87 (RECIST and ΔTvol). OS was associated with CMR (p = .03), ΔSUVmax (p = .003), ΔSUVgluc (p = .003), and RECIST (p = .046). CONCLUSION. Unlike CA 19-9 level, changes in metabolic metrics from PET/MRI and morphologic metrics from CT after NAT were associated with pathologic response and OS in patients with PDA, warranting prospective validation. CLINICAL IMPACT. Imaging metrics associated with pathologic response and OS in PDA could help guide clinical management and outcomes for patients with PDA who undergo emergency therapeutic interventions.

Targeting of the Hedgehog/GLI and mTOR pathways in advanced pancreatic cancer, a phase 1 trial of Vismodegib and Sirolimus combination.

BACKGROUND/OBJECTIVES: Preclinical data indicated a functional and molecular interaction between Hedgehog (HH)/GLI and PI3K-AKT-mTOR pathways promoting pancreatic ductal adenocarcinoma (PDAC). A phase I study was conducted of Vismodegib and Sirolimus combination to evaluate maximum tolerated dose (MTD) and preliminary anti-tumor efficacy. METHODS: Cohort I included advanced solid tumors patients following a traditional 3 + 3 design. Vismodegib was orally administered at 150 mg daily with Sirolimus starting at 3 mg daily, increasing to 6 mg daily at dose level 2. Cohort II included only metastatic PDAC patients. Anti-tumor efficacy was evaluated every two cycles and target assessment at pre-treatment and after a single cycle. RESULTS: Nine patient were enrolled in cohort I and 22 patients in cohort II. Twenty-eight patients were evaluated for dose-limiting toxicities (DLTs). One DLT was observed in each cohort, consisting of grade 2 mucositis and grade 3 thrombocytopenia. The MTD for Vismodegib and Sirolimus were 150 mg daily and 6 mg daily, respectively. The most common grade 3-4 toxicities were fatigue, thrombocytopenia, dehydration, and infections. A total of 6 patients had stable disease. No partial or complete responses were observed. Paired biopsy analysis before and after the first cycle in cohort II consistently demonstrated reduced GLI1 expression. Conversely, GLI and mTOR downstream targets were not significantly affected. CONCLUSIONS: The combination of Vismodegib and Sirolimus was well tolerated. Clinical benefit was limited to stable disease in a subgroup of patients. Targeting efficacy demonstrated consistent partial decreases in HH/GLI signaling with limited impact on mTOR signaling. These findings conflict with pre-clinical models and warrant further investigations.

Rheumatoid pulmonary nodules: clinical and imaging features compared with malignancy.

OBJECTIVES: The objective of this study was to identify clinical and imaging features that distinguish rheumatoid lung nodules from malignancy. METHODS: We conducted a retrospective review of 73 rheumatoid patients with histologically-proven rheumatoid and malignant lung nodules encountered at Mayo Clinic, Rochester, MN (2001-2016). Medical records and imaging were reviewed including a retrospective blinded review of CT and PET/CT studies. RESULTS: The study cohort had a mean age of 67 ± 11 years (range 45-86) including 44 (60%) women, 82% with a smoking history, 38% with subcutaneous rheumatoid nodules, and 78% with rheumatoid factor seropositivity. Subjects with rheumatoid lung nodules compared to malignancy were younger (59 ± 12 vs 71 ± 9 years, p < 0.001), more likely to manifest subcutaneous rheumatoid nodules (73% vs 20%, p < 0.001) and rheumatoid factor seropositivity (93% vs 68%, p = 0.034) but a history of smoking was common in both groups (p = 0.36). CT features more commonly associated with rheumatoid lung nodules compared to malignancy included multiplicity, smooth border, cavitation, satellite nodules, pleural contact, and a subpleural rind of soft tissue. Optimal sensitivity (77%) and specificity (92%) (AUC 0.85, CI 0.75-0.94) for rheumatoid lung nodule were obtained with ≥ 3 CT findings (≥ 4 nodules, peripheral location, cavitation, satellite nodules, smooth border, and subpleural rind). Key 18FDG-PET/CT features included low-level metabolism (SUVmax 2.7 ± 2 vs 7.2 ± 4.8, p = 0.007) and lack of 18F-fluorodeoxyglucose (FDG)-avid draining lymph nodes. CONCLUSION: Rheumatoid lung nodules have distinct CT and PET/CT features compared to malignancy. Patients with rheumatoid lung nodules are younger and more likely to manifest subcutaneous rheumatoid nodules and seropositivity. KEY POINTS: • Rheumatoid lung nodules have distinct clinical and imaging features compared to lung malignancy. • CT features of rheumatoid lung nodules include multiplicity, cavitation, satellite nodules, smooth border, peripheral location, and subpleural rind. • Key PET/CT features include low-level metabolism and lack of FDG-avid draining lymph nodes.

Role of 18F-FDG PET/CT in the diagnosis of cardiovascular implantable electronic device infections: A meta-analysis.

OBJECTIVE: We performed a meta-analysis evaluating the use of fluorine-18-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) in the diagnosis of cardiovascular implantable electronic device (CIED) infections. BACKGROUND: PET/CT may be helpful in the diagnosis of CIED infection, particularly in patients with the absence of localizing signs or definitive echocardiographic findings. METHODS: PubMed, Embase, Cochrane library, CINAHL, Web of Knowledge, and www.clinicaltrials.gov from January 1990 to April 2017 were searched for studies evaluating the accuracy of PET/CT in the diagnosis of CIED infections. RESULTS: Overall, 14 studies involving 492 patients were included in the meta-analysis. The pooled sensitivity of PET/CT for diagnosis of CIED infection was 83% (95% CI 78%-86%) and the pooled specificity was 89% (95% CI 84%-94%). PET/CT demonstrated a higher sensitivity of 96% (95% CI 86%-99%) and specificity of 97% (95% CI 86%-99%) for diagnosis of pocket infections. Diagnostic accuracy for lead infections or CIED-IE was lower with pooled sensitivity of 76% (95% CI 65%-85%) and specificity of 83% (95% CI 72%-90%). CONCLUSION: Use of PET/CT in the evaluation of CIED infection has both a high sensitivity (83%) and specificity (89%) and deserves consideration in the management of selected patients with suspected CIED infections.

Identification of Recurrence Sites Following Post-Prostatectomy Treatment for Prostate Cancer Using 11C-Choline Positron Emission Tomography and Multiparametric Pelvic Magnetic Resonance Imaging.

PURPOSE: We describe anatomical sites of recurrence in patients with prostate cancer who had biochemical recurrence following radical prostatectomy and who received radiotherapy and/or androgen deprivation therapy postoperatively. We performed 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging. MATERIALS AND METHODS: After radiotherapy and/or androgen deprivation therapy patients who underwent radical prostatectomy were evaluated by 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging to determine recurrence patterns and clinicopathological features. Recurrent sites were described as local only (seminal vesicle bed/prostate fossa, vesicourethral anastomosis and bladder neck) or distant metastatic disease. Features associated with the identification of any distant metastatic disease were evaluated by multivariable logistic regression. RESULTS: A total of 550 patients were identified. Treatment included androgen deprivation therapy in 108, radiotherapy in 201, and androgen deprivation therapy and radiotherapy in 241. Median prostate specific antigen at evaluation was 3.9, 3.6 and 2.8 ng/ml in patients treated with androgen deprivation therapy, radiotherapy and a combination, respectively. Recurrence developed locally in 77 patients (14%), as distant metastasis only in 411 (75%), and as local and distant metastatic disease in 62 (11%). On multivariable analysis treatment with radiotherapy (OR 7.18, 95% CI 2.92-17.65), and radiotherapy and hormonal therapy (OR 9.23, 95% CI 3.90-21.87, all p <0.01) was associated with increased odds of distant failure at evaluation. CONCLUSIONS: The combination of 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging successfully identified patterns of recurrence after postoperative radiotherapy and/or androgen deprivation therapy at a median prostate specific antigen of less than 4 ng/ml. Half of this cohort had local only recurrence and/or a low disease burden limited to pelvic lymph nodes. These patients may benefit from additional local therapy. These data and this analysis may facilitate the evaluation of such patients with biochemically recurrent prostate cancer.

Pittsburgh compound B (PiB) PET imaging of meningioma and other intracranial tumors.

Meningiomas are the most common intracranial tumors. Diagnosis by MRI is generally straightforward, but lack of imaging specificity can present a diagnostic dilemma, particularly in patients with cancer. We report our experience with meningioma identification on Pittsburgh compound B (PiB) PET/CT. Patients who underwent PiB PET/CT from 2006 to 2015 were reviewed to identify those with intracranial tumors. Tumor types were classified by MR appearance, or by pathology when available. Maximum standardized uptake value (SUVmax) measurements of tumor PiB activity were compared across tumor types. 2472 patients underwent PiB PET/CT in the period of interest; 45 patients (1.8%) had probable or definite intracranial tumor. Tumor types were meningioma (29/45, 64%), vestibular schwannoma (7/45, 16%), pituitary macroadenoma (4/45, 9%), metastatic disease (2/45, 4%), and others (3/45, 7%). In patients with meningioma, the mean lesion SUVmax was 2.05 (SD 1.37), versus 1.00 (SD 0.42) in patients with non-meningioma tumors (p < 0.01). A receiver operating curve was created for lesion:cerebellum SUVmax ratio, with an area under the curve of 0.91 for a value of 1.68. At or above this ratio, specificity for meningioma was 100% (95% CI 79-100%) and sensitivity was 76% (95% CI 57-90%). PiB PET activity within an intracranial tumor is a highly specific and reasonably sensitive marker of meningioma. Further prospective evaluation is warranted to validate this result as well as to assess the performance of commercially available beta-amyloid radiotracers in meningioma identification.

Clinical PET/MRI: 2018 Update.

OBJECTIVE: The purpose of this article is to provide an update on clinical PET/MRI, including current and developing clinical indications and technical developments. CONCLUSION: PET/MRI is evolving rapidly, transitioning from a predominant research focus to exciting clinical practice. Key technical obstacles have been overcome, and further technical advances promise to herald significant advancements in image quality. Further optimization of protocols to address challenges posed by this hybrid modality will ensure the long-term success of PET/MRI.

11C-Choline PET/CT for Detection and Localization of Parathyroid Adenomas.

OBJECTIVE: The purpose of this study is to determine the efficacy of 11C-choline PET/CT for the detection of parathyroid adenomas by retrospectively reviewing a large patient population. MATERIALS AND METHODS: In this single-institution retrospective study, 7088 11C-choline PET/CT scans performed of 2933 men with prostate cancer from January 2005 through February 2016 were evaluated. Patients with suspected parathyroid adenomas were identified through a review of the electronic medical record and relevant imaging. Patient demographics, laboratory results, and lesion characteristics were noted. Pathologically proven parathyroid adenomas and lesions in patients with imaging or laboratory findings consistent with the diagnosis were considered positive. RESULTS: Thirteen men (mean [± SD] age, 72 ± 7 years) with pathologically or laboratory-proven parathyroid adenomas were identified. All had abnormally elevated serum calcium and parathyroid hormone levels. All adenomas were tracer avid on 11C-choline PET/CT (maximum standardized uptake value, 5.6 ± 3.0), with activity averaging 4.2 times that of the blood pool and 2.1 times that of the adjacent thyroid. One case of an ectopic adenoma was identified. Of the six pathologically confirmed cases, none displayed high-grade features such as capsular, vascular, or adjacent tissue invasion. Three additional patients with possible parathyroid adenomas at 11C-choline PET/CT were ultimately found to have thyroid lesions on the basis of tissue diagnosis; however, none of these patients had abnormal calcium or parathyroid hormone levels. CONCLUSION: In our patient population, 11C-choline PET/CT identified parathyroid adenomas with high specificity. Prospective investigation is warranted to validate this result and delineate the utility of 11C-choline PET/CT relative to other modalities.

PET/MRI: Where might it replace PET/CT?

Simultaneous positron emission tomography and MRI (PET/MRI) is a technology that combines the anatomic and quantitative strengths of MR imaging with physiologic information obtained from PET. PET and computed tomography (PET/CT) performed in a single scanning session is an established technology already in widespread and accepted use worldwide. Given the higher cost and complexity of operating and interpreting the studies obtained on a PET/MRI system, there has been question as to which patients would benefit most from imaging with PET/MRI versus PET/CT. In this article, we compare PET/MRI with PET/CT, detail the applications for which PET/MRI has shown promise and discuss impediments to future adoption. It is our hope that future work will prove the benefit of PET/MRI to specific groups of patients, initially those in which PET/CT and MRI are already performed, leveraging simultaneity and allowing for greater degrees of multiparametric evaluation. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1247-1262.

First PET Imaging Studies With 63Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease.

Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). 63Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. Dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of 63Zn-zinc citrate (∼330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics. Regional cerebral 63Zn clearances were compared with 11C-Pittsburgh Compound B (11C-PiB) and 18F-fluorodeoxyglucose (18F-FDG) imaging data. 63Zn-zinc citrate was well tolerated in human participants with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney, with moderate uptake being seen in intestines, prostate (in males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependencies were observed in 63Zn clearance kinetics in relationship with regions of high amyloid-ß plaque burden (11C-PiB) and 18F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe 63Zn-zinc citrate. Primary sites of uptake in the digestive system accent the role of zinc in gastrointestinal function. Preliminary information on zinc kinetics in patients with AD evidenced regional differences in clearance rates in correspondence with regional amyloid-ß pathology, warranting further imaging studies of zinc homeostasis in patients with AD.

Multimodality Imaging of Neurodegenerative Processes: Part 2, Atypical Dementias.

OBJECTIVE: The purpose of this article is to describe the role of multimodality imaging in the evaluation of atypical neurodegenerative conditions. An imaging approach to the more common dementia disease processes was described in part 1. This article, part 2, briefly discusses current Centers for Medicare & Medicaid Services coverage for imaging patients with dementia and illustrates the basic concepts of combining anatomic, metabolic, and amyloid imaging in the evaluation of patients with atypical neurodegenerative dementia. Although these disease processes are rare, the growing repertoire of clinically available imaging techniques necessitates an understanding of their imaging patterns. CONCLUSION: Despite the rarity of these conditions, imaging of patients with neurodegenerative disorders is on the rise, and familiarity with the imaging appearances of these atypical causes is increasingly important.

Multimodality Imaging of Neurodegenerative Processes: Part 1, The Basics and Common Dementias.

OBJECTIVE: Multimodality imaging plays an important role in the structural and functional characterization of neurodegenerative conditions. This article illustrates the basic concepts of anatomic, metabolic, and amyloid imaging and describes the application of a multimodality approach in the evaluation of patients with the more common neurodegenerative dementia processes. Proper utilization of clinically available imaging techniques allows greater insight into these common disease processes. CONCLUSION: Recognizing the strength of combined anatomic, metabolic, and amyloid imaging can allow a more complete and confident assessment of patients with common degenerative dementias. This added knowledge can improve clinical care, allow initiation of appropriate therapies and counseling, and improve prognostication.