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Please see the Editorial Comment by Jennifer Schroeder discussing this article. The introduction of immunotherapy with immune-checkpoint inhibitors (ICIs) has revolutionized cancer treatment paradi...

Neoadjuvant immune checkpoint blockade represents a novel approach for potentially decreasing the risk of recurrence in patients with nonmetastatic renal cell carcinoma (RCC). In this early phase clincal tiral, we evaluated the safety and tolerability of neoadjuvant treatment with the programmed cell death protein 1 (PD-1) inhibitor nivolumab in patients with nonmetastatic high-risk RCC. Nonprimary endpoints included objective radiographic tumor response rate, immune-related pathologic response rate, quality of life alterations, and metastasis-free and overall survival. In total, 17 patients were enrolled in this study and underwent surgery without a delay after receiving three every-2-wk doses of neoadjuvant nivolumab. Adverse events (AEs) of any grade occurred in 14 (82.4%) patients, with two (11.8%) experiencing grade 3 events. Ten (58.8%) patients experienced an AE of any grade potentially attributable to nivolumab (all grade 1–2), and no grade 4–5 AEs occurred regardless of treatment attribution. The most common AEs were grade 1 fatigue (41.2%), grade 1 pruritis (29.4%), and grade 1 rash (29.4%). All evaluable patients had stable disease as per established radiographic criteria, with one (6.7%) demonstrating features of an immune-related pathologic response. Quality of life remained stable during treatment, with improvements relative to baseline noted at ≥6 mo postoperatively. Metastasis-free survival and overall survival were 85.1% and 100% at 2 yr, respectively. Patient summary In this study, we evaluated the safety and tolerability of preoperative administration of three doses of the immune checkpoint inhibitor nivolumab in patients with clinically localized high-risk renal cell carcinoma. We demonstrated the safety of this approach and found that, although most patients will not experience a radiographic response to treatment, a subset may have features of an immune-related pathologic response.

18F-DCFPyL was recently approved by the FDA for evaluation prior to definitive therapy and for biochemical recurrence. Here we focus on the key data that justify the clinical use of 18F-DCFPyL, as well as those aspects of protocol implementation and image interpretation that are important to the nuclear medicine physicians and radiologists who will interpret 18F-DCFPyL PET/CT and PET/MR scans.

Background Incidentally detected small renal masses (SRMs) may be one of several benign or malignant tumor histologies, and are heterogeneous in oncologic potential. Renal mass biopsy can be used to determine the histology of SRMs. However, this invasive approach has significant limitations. Technetium-99m sestamibi single photon emission computed tomography/computed tomography (99mTc-sestamibi SPECT/CT) is a promising imaging tool that can aid in identifying benign renal oncocytomas and hybrid oncocytic/chromophobe tumors. Objective To evaluate the clinical and economic value of 99mTc-sestamibi SPECT/CT in guiding the management of SRMs. Design, setting, and participants We developed a decision analysis model to estimate the costs and health outcomes of competing management strategies for a healthy 65-yr-old patient with an asymptomatic SRM. Intervention Empiric surgery (reference); real-world clinical practice (RWCP) consisting of empiric surgery, thermal ablation, and active surveillance (alternative reference); renal mass biopsy (option 1); 99mTc-sestamibi SPECT/CT (option 2); and 99mTc-sestamibi SPECT/CT followed by biopsy to confirm benign SRMs (option 3). Outcome measurements and statistical analysis We assessed lifetime health utilities, measured in quality-adjusted life years (QALYs), and direct medical costs from a health payer perspective. We calculated the incremental cost-effectiveness ratio (ICER) for options 1–3 versus the reference and alternative reference arms, with a willingness-to-pay threshold of $50 000/QALY. Univariate, multivariate, and probabilistic sensitivity analyses were performed. Results and limitations Option 3 had a very low risk of untreated malignant tumors (0.2%, vs 2.1% for option 1, 4.2% for option 2, and 0% for empiric surgery) and the highest probability of leaving benign tumors untreated (84.4%, vs 53.9% for option 1, 51.7% for option 2, and 0% for empiric surgery). Option 3 dominated empiric surgery and options 1 and 2 (ie, lower costs and higher QALYs). Compared with RWCP, options 1–3 were all cost effective; option 3 had the lowest ICER of $18 821/QALY. These findings were robust to alternative input values. Study limitations included data uncertainties and a limited number of centers from which 99mTc-sestamibi SPECT/CT performance data were collected. Conclusions 99mTc-sestamibi SPECT/CT followed by confirmatory biopsy helps avoid surgery for benign SRMs, minimizes untreated malignant SRMs, and is cost effective compared with existing strategies. Patient summary Our research suggests that by using a noninvasive imaging test, known as technetium-99m sestamibi single photon emission computed tomography/computed tomography, to diagnose small renal masses, urologists may avoid unnecessary surgery for benign tumors and minimize the risk of leaving a malignant tumor untreated. Moreover, the use of this strategy to diagnose small renal masses is cost effective for the health care system.

CONTEXT: Castration-resistant prostate cancer (CRPC) treatment is an evolving challenge. Prostate-specific membrane antigen (PSMA)-targeted endoradiotherapy/radioligand therapy (PRLT) with small-molecule, urea-based agents labeled with the β-particle–emitting radionuclide lutetium-177 ((177)Lu) is a promising new approach. OBJECTIVE: In this systematic review and meta-analysis, we evaluated the efficacy and toxicity of PRLT. EVIDENCE ACQUISITION: A systematic search was performed in PubMed/Medline (last updated February 18, 2019). A total of 250 studies were reviewed, and 24 studies with 1192 patients were included in the analysis. Proportions of patients with ≥50% serum prostate-specific antigen (PSA) decrease, any PSA decrease, and any PSA increase were extracted. Proportions of patients showing any grade toxicity and those with grade 3/4 toxicities based on Common Terminology Criteria for Adverse Events (CTCAE) grading were extracted from manuscripts. Overall survival and progression-free survival were evaluated. A meta-analysis of single proportions was carried out. Furthermore, we compared the two most common PRLT agents, (177)Lu-PSMA with (177)Lu-PSMA-I&T, for effectiveness and toxicity. EVIDENCE SYNTHESIS: Among the 24 included studies, 20 included data on (177)Lu-PSMA-617, three included data on (177)Lu-PSMA-I&T, and one study had aggregated data for (177)Lu-PSMA-617 and (177)Lu-PSMA-I&T. The estimated proportion of (177)Lu-PSMA-617–treated patients who showed a serum PSA decrease of ≥50% with at least an 8-wk interval between therapy and PSA measurement was 0.44 (0.39; 0.50). Therapy with (177)Lu-PSMA-I&T demonstrated an estimated proportion of patients with ≥50% PSA reduction to be 0.36 (0.26; 0.47). The aggregate results for men treated with more than one cycle of any kind of PRLT showed an estimated proportion of 0.46 (0.41; 0.51) for PSA response ≥50%. Regarding aggregate data from all of the PRLT agents, we found that grade 3 and 4 toxicities were uncommon, with estimated proportions from 0.01 (0.00;0.04) for nausea, fatigue, diarrhea, and elevated aspartate transaminase up to 0.08 (0.05; 0.12) for anemia. There was considerable heterogeneity among the studies in the “any-grade toxicity” groups. Meta-regression showed that more than one cycle of PRLT is associated with a greater proportion of patients with ≥50% PSA reduction. Overall survival according to pooled hazard ratios (HRs) for any PSA decline was 0.29 (0.18; 0.46), and for >50% PSA reduction was 0.67 (0.43; 1.07). Progression-free survival according to a pooled HR of >50% PSA reduction was 0.53 (0.32; 0.86). CONCLUSIONS: The relatively high number of PSA responders alongside the low rate of severe toxicity reflects the potentially promising role of PRLT in treating CRPC. The ultimate utility of this treatment modality will become clearer as multiple prospective studies continue to accrue. In the interim, this systematic review and meta-analysis can serve as a compendium of effectiveness and adverse events associated with PRLT for treating clinicians. PATIENT SUMMARY: Prostate-specific membrane antigen–targeted endoradiotherapy/radioligand therapy (PRLT) is associated with ≥50% reduction in prostate-specific antigen level in a large number of patients and a low rate of toxicity, reflecting its potential in treating castration-resistant prostate cancer. This systematic review and meta-analysis presents as a compendium of the effectiveness and adverse events related to PRLT for treating clinicians.

To discuss the potential utility of newer imaging modalities including micro-ultrasound and PSMA-PET for the detection of clinically significant prostate cancer, technologies that may gain roles as adjuncts to multiparametric magnetic resonance imaging (mpMRI) in the active surveillance (AS) setting. Narrative review of two new imaging modalities used for primary prostate cancer through April 2021. A targeted search was performed to identify current relevant literature on the role of new imaging modalities for primary prostate cancer using search terms “micro-ultrasound,” “molecular imaging,” “prostate cancer,” “active surveillance,” “multiparametric MRI,” “PI-RADS,” “PRI-MUS,” and “detection rate.” In addition, references of included articles were screened for further relevant publications. Micro-ultrasound (micro-US) and prostate-specific membrane antigen-positron emission tomography (PSMA-PET) are increasing in their use and applicability to prostate cancer imaging. Micro-US is used for cancer detection and may identify higher grade cancers more accurately than conventional ultrasound, despite technical hurdles in its initial launch. PSMA-PET is highly sensitive and specific for high-grade and metastatic prostate cancer, though costly and not easily available. Though data are sparse, it may have an emerging role in cancer diagnosis in select localized cases, and in some men considering (or currently on) AS who have indications of more aggressive disease. There are very limited data on micro-US and PSMA-PET in AS patients. However, given the ability of these modalities to identify high-grade cancer, their judicious use in AS patients may be of utility in the future.

18F-Fluciclovine PET imaging has been increasingly used in the restaging of prostate cancer patients with biochemical recurrence (BCR); however, its clinical utility in patients with low prostate-specific antigen (PSA) levels following primary radiation therapy has not been well-studied. This study aims to determine the detection rate and diagnostic accuracy of 18F-fluciclovine PET and the patterns of prostate cancer recurrence in patients with rising PSA after initial radiation therapy, particularly in patients with PSA levels below the accepted Phoenix definition of BCR (PSA nadir +2 ng/mL). This retrospective study included patients from two tertiary institutions who underwent 18F-fluciclovine PET scans for elevated PSA level following initial external beam radiation therapy, brachytherapy, and/or proton therapy. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine the diagnostic accuracy of 18F-fluciclovine PET and associations of PSA kinetic parameters with 18F-fluciclovine PET outcome. One hundred patients were included in this study. The overall detection rate on a patient-level was 79% (79/100). 18F-Fluciclovine PET was positive in 62% (23/37) of cases with PSA below the Phoenix criteria. The positive predictive value of 18F-fluciclovine PET was 89% (95% CI: 80–94%). In patients with PSA below the Phoenix criteria, the PSA velocity had the highest predictive value of 18F-fluciclovine PET outcome. PSA doubling time (PSADT) and PSA velocity were associated with the presence of extra-pelvic metastatic disease. 18F-Fluciclovine PET can identify recurrent disease at low PSA level and PSA rise below accepted Phoenix criteria in patients with suspected BCR after primary radiation therapy, particularly in patients with low PSADT or high PSA velocity. In patients with low PSADT or high PSA velocity, there is an increased probability of extra-pelvic metastases. Therefore, these patients are more likely to benefit from PET/CT or PET/MRI than pelvic MRI alone.

Background Diagnosis of Parkinson’s disease (PD) is informed by the presence of progressive motor and non-motor symptoms and by imaging dopamine transporter with [123I]ioflupane (DaTscan). Deep learning and ensemble methods have recently shown promise in medical image analysis. Therefore, this study aimed to develop a three-stage, deep learning, ensemble approach for prognosis in patients with PD. Methods Retrospective data of 198 patients with PD were retrieved from the Parkinson’s Progression Markers Initiative database and randomly partitioned into the training, validation, and test sets with 118, 40, and 40 patients, respectively. The first and second stages of the approach extracted features from DaTscan and clinical measures of motor symptoms, respectively. The third stage trained an ensemble of deep neural networks on different subsets of the extracted features to predict patient outcome 4 years after initial baseline screening. The approach was evaluated by assessing mean absolute percentage error (MAPE), mean absolute error (MAE), Pearson’s correlation coefficient, and bias between the predicted and observed motor outcome scores. The approach was compared to individual networks given different data subsets as inputs. Results The ensemble approach yielded a MAPE of 18.36%, MAE of 4.70, a Pearson’s correlation coefficient of 0.84, and had no significant bias indicating accurate outcome prediction. The approach outperformed individual networks not given DaTscan imaging or clinical measures of motor symptoms as inputs, respectively. Conclusion The approach showed promise for longitudinal prognostication in PD and demonstrated the synergy of imaging and non-imaging information for the prediction task.

This review highlights the 2 major molecular imaging modalities that are used in clinics, namely single-photon emission computed tomography (SPECT) and positron emission tomography (PET), and their added value in management of patients with brain tumors. There are a variety of SPECT and PET radiotracers that can allow imaging of different molecular processes. Those radiotracers target specific molecular features of tumors, resulting in improved specificity of these agents. Potential applications include staging of brain tumors and evaluating post-therapeutic changes.

Increasing use and resolution of testicular ultrasound imaging has resulted in a greater diagnosis of non-palpable small testicular masses and subsequent over-treatment with orchiectomy. Our aim was to determine the diagnostic accuracy of testicular ultrasound to accurately determine the pathologic size of small testicular masses (SMTMs) and to evaluate the association of various measurements with benign pathology. Retrospectively, an institutional testicular cancer database was reviewed to evaluate the patients who underwent an orchiectomy for a testicular mass seen on ultrasound from 2003 to 2017. Three-dimensional measurements were compared from the ultrasound and pathology specimens, including other measures such as tumor volume and percentage of testicular volume. Finally, the predictive accuracy of maximum diameter and tumor volume to predict benign pathology was evaluated using receiver-operating curve analysis. We identified 208 patients and showed that ultrasound significantly underestimated sub-centimeter testicular masses (mean difference 0.56 cm, 95%CI 0.89–0.14, p = 0.004) and testicular masses between 1 and

[111 In]In-XYIMSR-01 is a promising single-photon emission computed tomography (SPECT) imaging agent for identification of tumors that overexpress carbonic anhydrase IX. To translate [111 In]In-XYIMSR-01 to phase I trials, we performed animal toxicity and dosimetry studies, determined the maximum dose for human use, and completed the chemistry, manufacturing, and controls component of a standard regulatory application. The production process, quality control testing, stability studies, and specifications for sterile drug product release were based on United States Pharmacopeia chapters and , FDA 21 CFR Part 212. Toxicity was evaluated by using nonradioactive [113/115 In]In-XYIMSR-01 according to 21 CFR Part 58 guidelines. Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) was used to calculate the maximum single dose for human studies. Three process validation runs at starting radioactivities of ~800 MBq were completed with a minimum concentration of 407 MBq/ml and radiochemical purity of ≥99% at the end of synthesis. A single intravenous dose of 55 μg/ml of [113/115 In]In-XYIMSR-01 was well tolerated in male and female Sprague-Dawley rats. The calculated maximum single dose for human injection from dosimetry studies was 390.35 MBq of [111 In]In-XYIMSR-01. We have completed toxicity and dosimetry studies as well as validated a manufacturing process to test [111 In]In-XYIMSR-01 in a phase I clinical trial.

Upper urinary tract obstructions (UTOs) are blockages that inhibit the flow of urine through its normal course, leading to impaired kidney function. Imaging plays a significant role in the initial diagnosis of UTO, with anatomic imaging (primarily ultrasound (US) and non-contrast computed tomography (CT)) serving as screening tools for the detection of the dilation of the urinary collecting systems (i.e., hydronephrosis). Whether hydronephrosis represents UTO or a non-obstructive process is determined by functional imaging (typically nuclear medicine renal scintigraphy). If these exams reveal evidence of UTO but no discernable source, multiphase contrast enhanced CT urography and/or dynamic contrast enhanced MR urography (DCE-MRU) may be performed to delineate a cause. These are often performed in conjunction with direct ureteroscopic evaluation. While contrast-enhanced CT currently predominates, it can induce renal injury due to contrast induced nephropathy (CIN), subject patients to ionizing radiation and is limited in quantifying renal function (traditionally assessed by renal scintigraphy) and establishing the extent to which hydronephrosis is due to functional obstruction. Traditional MRI is similarly limited in its ability to quantify function. DCE-MRU presents concerns regarding nephrogenic systemic fibrosis (NSF), although decreased with newer gadolinium-based contrast agents, and regarding cumulative gadolinium deposition in the basal ganglia. DCE-MR CEST urography is a promising alternative, employing new MRI contrast agents and imaging schemes and allowing for concurrent assessment of renal anatomy and functional parameters. In this review we highlight clinical challenges in the diagnosis and management of UTO, identify key advances in imaging agents and techniques for DCE-MR CEST urography and provide perspective on how this technique may evolve in clinical importance.

Purpose: Current FDA-approved imaging modalities are inadequate for localizing prostate cancer biochemical recurrence (BCR). 18F-DCFPyL is a highly selective, small-molecule prostate-specific membrane antigen–targeted PET radiotracer. CONDOR was a prospective study designed to determine the performance of 18F-DCFPyL-PET/CT in patients with BCR and uninformative standard imaging. Experimental Design: Men with rising PSA ≥0.2 ng/mL after prostatectomy or ≥2 ng/mL above nadir after radiotherapy were eligible. The primary endpoint was correct localization rate (CLR), defined as positive predictive value with an additional requirement of anatomic lesion colocalization between 18F-DCFPyL-PET/CT and a composite standard of truth (SOT). The SOT consisted of, in descending priority (i) histopathology, (ii) subsequent correlative imaging findings, or (iii) post-radiation PSA response. The trial was considered a success if the lower bound of the 95% confidence interval (CI) for CLR exceeded 20% for two of three 18F-DCFPyL-PET/CT readers. Secondary endpoints included change in intended management and safety. Results: A total of 208 men with a median baseline PSA of 0.8 ng/mL (range: 0.2–98.4 ng/mL) underwent 18F-DCFPyL-PET/CT. The CLR was 84.8%–87.0% (lower bound of 95% CI: 77.8–80.4). A total of 63.9% of evaluable patients had a change in intended management after 18F-DCFPyL-PET/CT. The disease detection rate was 59% to 66% (at least one lesion detected per patient by 18F-DCFPyL-PET/CT by central readers). Conclusions: Performance of 18F-DCFPyL-PET/CT achieved the study’s primary endpoint, demonstrating disease localization in the setting of negative standard imaging and providing clinically meaningful and actionable information. These data further support the utility of 18F-DCFPyL-PET/CT to localize disease in men with recurrent prostate cancer. See related commentary by True and Chen, p. 3512

Purpose: Positron emission tomography (PET) with small molecules targeting prostate-specific membrane antigen (PSMA) is being adopted as a clinical standard for prostate cancer (PCa) imaging. In this study, we evaluated changes in uptake on PSMA-targeted PET in men starting abiraterone or enzalutamide. Methods: This prospective, single-arm, two-center, exploratory clinical trial enrolled men with metastatic castration-resistant prostate cancer (CRPC) initiating abiraterone or enzalutamide. Each patient was imaged with 18F-DCFPyL at baseline and within 2-4 months after starting therapy. Patients were followed for up to 48 months from enrollment. A central review evaluated baseline and follow-up PET scans recording change in maximum standardized uptake value (SUVmax) at all disease sites and classifying the pattern of change. Two parameters: the delta percent SUVmax (DPSM) of all lesions and the delta absolute SUVmax (DASM) of all lesions were derived. Kaplan-Meier curves were used to estimate time to therapy change (TTTC) and overall survival (OS). Results: Sixteen evaluable patients were accrued to the study. Median TTTC was 9.6 months (95% confidence interval (CI), 6.9-14.2) and median OS was 28.6 months (95% CI 18.3-not available (N/A)). Patients with a mixed-but-predominantly-increased pattern of radiotracer uptake had shorter TTTC and OS. Men with low DPSM had median TTTC 12.2 months (95% CI 11.3-N/A) and median OS 37.2 months (95% CI 28.9-N/A), while those with high DPSM had median TTTC 6.5 months (95% CI 4.6-N/A, P = 0.0001) and median OS 17.8 months (95% CI 13.9-N/A, P = 0.02). Men with low DASM had median TTTC 12.2 months (95% CI 11.3-N/A) and median OS N/A (95% CI 37.2 months-N/A), while those with high DASM had median TTTC 6.9 months (95% CI 6.1-N/A, P = 0.003) and median OS 17.8 months (95% CI 13.9-N/A, P = 0.002). Conclusion: Findings on PSMA-targeted PET 2-4 months after initiation of abiraterone or enzalutamide are associated with TTTC and OS. Development of new lesions and/or increasing intensity of radiotracer uptake at sites of baseline disease are poor prognostic findings suggesting shorter TTTC and OS.

Brown adipose tissue (BAT) is involved in energy dissipation and has been linked to weight loss, insulin sensitivity, and reduced risk of atherosclerotic disease. BAT is found most often in the supraclavicular region, as well as mediastinal and paravertebral areas, and it is predominantly seen in young persons. BAT is activated by cold temperature and the sympathetic nervous system. In humans, BAT was initially detected via 2-deoxy-2-[18 F]fluoro-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT), a high-resolution molecular imaging modality used to identify and stage malignancies. Recent studies have shown that BAT can be localized using conventional imaging modalities, such as CT or magnetic resonance imaging, as well as radiotracers used for single-photon emission CT. In this systematic review, we have summarized the evidence for BAT detection in humans using various imaging techniques.

Rationale: Bipolar androgen therapy (BAT) is an emerging treatment for metastatic castration resistant prostate cancer (mCRPC). 18F-DCFPyL is a small-molecule positron emission tomography (PET) radiotracer targeting prostate-specific membrane antigen (PSMA). We analyzed the utility of 18F-DCFPyL PET/CT in determining clinical response to BAT. Methods: Six men with mCRPC receiving BAT were imaged with 18F-DCFPyL PET/CT at baseline and after 3 months of treatment. Progression by PSMA-targeted PET/CT was defined as the appearance of any new 18F-DCFPyL-avid lesion. Results: Three of 6 (50%) patients had progression on 18F-DCFPyL PET/CT. All three had stable disease or better on contemporaneous conventional imaging. Radiographic progression on CT and/or bone scan was observed within 3 months of progression on 18F-DCFPyL PET/CT. For the 3 patients that did not have progression on 18F-DCFPyL PET/CT, radiographic progression was not observed for > 6 months. Conclusion: New radiotracer-avid lesions on 18F-DCFPyL PET/CT in men with mCRPC undergoing BAT can indicate early progression.

Background The purpose of this study is to assess the body composition changes in men with recently diagnosed oligometastatic prostate cancer following neoadjuvant chemohormonal therapy. Further, we evaluated whether CT‐based body composition parameters are associated with biochemical recurrence or imaging progression. Material and methods Recently diagnosed castration‐naïve oligometastatic prostate cancer patients who received neoadjuvant docetaxel chemotherapy and androgen deprivation treatment (ADT) before prostatectomy and consolidation of local and oligometastatic disease (total eradication therapy), as part of a phase‐II prospective clinical trial were included. Body composition parameters including cross‐sectional areas of the psoas muscle, total, visceral, and subcutaneous adipose tissue were measured on serial CT scans obtained before and following completion of neoadjuvant treatment. Results A total of 22 prostate cancer patients were included (median age 58 years, median Gleason score 8). The median time intervals between commencement of neoadjuvant chemohormonal therapy and first and second follow‐up CTs were 3 and 12 months, respectively. Compared to the baseline scan, there were significant declines in psoas muscle cross‐sectional areas with estimated percentage declines of −13.9% (IQR: 7.6%–16.5%, p

This review covers the state-of-the-art imaging in therapy assessment and surveillance of lung cancer with focus on the utility of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). We review different qualitative and quantitative response assessment criteria in lung cancer, common pitfalls and atypical patterns of response to immunotherapy, and imaging features of common immune-related adverse events. In addition, the currently recommended imaging workup in surveillance of asymptomatic patients with non-small-cell and small-cell lung cancer and future developments will be discussed.

PURPOSE: Prostate specific membrane antigen targeted (18)F-DCFPyL positron emission tomography/computerized tomography may offer superior image quality and sensitivity for the detection of biochemically recurrent prostate cancer. We examined the association of Gleason sum, serum prostate specific antigen and prostate specific antigen doubling time with any detectable and pelvic confined disease in patients with biochemically recurrent prostate cancer. MATERIALS AND METHODS: Data from 108 patients with biochemically recurrent prostate cancer after radical prostatectomy who underwent prostate specific membrane antigen targeted (18)F-DCFPyL positron emission tomography/computerized tomography were analyzed. Data were collected on positive positron emission tomography findings as well as pelvic confined disease. Associations between Gleason sum, prostate specific antigen and prostate specific antigen doubling time were retrospectively explored. RESULTS: Serum prostate specific antigen was associated with positive prostate specific membrane antigen targeted imaging as continuous (OR 3.08, 95% CI 1.60–7.95, p=0.005) and categorical values (ie prostate specific antigen greater than 2.0 to 5.0 vs 0.5 ng/ml or less, OR 16.92, 95% CI 3.13–315.81, p=0.008). No relationship between Gleason sum or prostate specific antigen doubling time with overall positive imaging was observed. Patients with a prostate specific antigen greater than 2.0 to 5.0 ng/ml were significantly less likely to be diagnosed with pelvic confined disease compared with the 0.5 ng/ml or less subgroup (OR 0.21, 95% CI 0.06–0.69, p=0.013). A prostate specific antigen doubling time of 9 months or more (OR 4.20, 95% CI 1.57–11.89, p=0.005) or prostate specific antigen doubling time of 12 months or more (OR 3.03, 95% CI 1.12–8.76, p=0.033) was significantly associated with pelvic confined disease. No relationship between Gleason sum and pelvic confined disease was observed. CONCLUSIONS: Absolute prostate specific antigen was positively associated with the presence of findings on prostate specific membrane antigen targeted imaging and negatively associated with pelvic confined disease. Prostate specific antigen doubling time did not predict for overall disease detection, but long prostate specific antigen doubling times were associated with pelvic confined prostate cancer.

Recently, a standardized framework system for interpreting somatostatin receptor (SSTR)–targeted PET/CT, termed the SSTR reporting and data system (RADS) 1.0, was introduced, providing reliable standards and criteria for SSTR-targeted imaging. We determined the interobserver reliability of SSTR-RADS for interpretation of (68)Ga-DOTATOC PET/CT scans in a multicentric, randomized setting. Methods: A set of 51 randomized (68)Ga-DOTATOC PET/CT scans was independently assessed by 4 masked readers with different levels of experience (2 experienced readers and 2 inexperienced readers) trained on the SSTR-RADS 1.0 criteria (based on a 5-point scale from 1 [definitively benign] to 5 [high certainty that neuroendocrine neoplasia is present]). For each scan, SSTR-RADS scores were assigned to a maximum of 5 target lesions (TLs). An overall scan impression based on SSTR-RADS was indicated, and interobserver agreement rates on a TL-based, on an organ-based, and on an overall SSTR-RADS score–based level were computed. The readers were also asked to decide whether peptide receptor radionuclide therapy (PRRT) should be considered on the basis of the assigned RADS scores. Results: Among the selected TLs, 153 were chosen by at least 2 readers (all 4 readers selected the same TLs in 58 of 153 [37.9%] instances). The interobserver agreement for SSTR-RADS scoring among identical TLs was good (intraclass correlation coefficient [ICC] ≥ 0.73 for 4, 3, and 2 identical TLs). For lymph node and liver lesions, excellent interobserver agreement rates were derived (ICC, 0.91 and 0.77, respectively). Moreover, the interobserver agreement for an overall scan impression based on SSTR-RADS was excellent (ICC, 0.88). The SSTR-RADS–based decision to use PRRT also demonstrated excellent agreement, with an ICC of 0.80. No significant differences between experienced and inexperienced readers for an overall scan impression and TL-based SSTR-RADS scoring were observed (P ≥ 0.18), thereby suggesting that SSTR-RADS seems to be readily applicable even for less experienced readers. Conclusion: SSTR-RADS–guided assessment demonstrated a high concordance rate, even among readers with different levels of experience, supporting the adoption of SSTR-RADS for trials, clinical routine, or outcome studies.

Utilizing complex lighting models, cinematic rendering is a novel technique for demonstrating computed tomography data with exquisite 3D anatomic detail. The tracheal lumen, tracheal wall, and adjacent soft tissue structures are represented with photorealistic detail exceeding that of conventional volume rendering or virtual bronchoscopy techniques. We applied cinematic rendering to a spectrum of emergent tracheal pathologies: traumatic tracheal tears, tracheoesophageal fistulas, tracheal foreign bodies, tracheal stenosis (intrinsic and extrinsic causes), tracheal neoplasms, and tracheomalacia. Cinematic rendering images enable visually accessible evaluation and comprehensive understanding of acute tracheal pathology, which is likely to be of value to both interventional pulmonologists and thoracic surgeons who are determining patient treatment plans.

We present a case of a 53-year-old woman with metastatic neuroendocrine tumor, presumed primary in the small intestine with metastases to the liver and mesenteric lymph nodes. The patient was being treated with lanreotide and followed with somatostatin receptor (SSTR)-targeted 68Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N', N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotate (68Ga-DOTATATE) positron emission tomography - computed tomography (PET/CT). On a follow-up exam, the patient's primary and metastatic disease had improved but she had new 68Ga-DOTATATE-avid lesions in the right breast and right axilla. Subsequent breast imaging workup and biopsy demonstrated a primary breast cancer and axillary lymph node metastasis.

Background Metastasis directed therapy (MDT) for patients with oligometastatic disease is associated with improvements in progression free survival (PFS) and overall survival (OS) compared to systemic therapy alone. Additionally, within a prostate-cancer-specific cohort, MDT is able to forestall initiation of androgen deprivation therapy (ADT) in men with hormone-sensitive, oligometastatic prostate cancer (HSOPCa) compared to observation. While MDT appears to be safe and effective in HSOPCa, a large percentage of men will eventually have disease recurrence. Patterns of failure in HSOPCa demonstrate patients tend to have recurrence in the bone following MDT, raising the question of sub-clinically-apparent osseous disease. Radium-223 dichloride is a radiopharmaceutical with structural similarity to calcium, allowing it to be taken up by bone where it emits alpha particles, and therefore might have utility in the treatment of micrometastatic osseous disease. Therefore, the primary goal of the phase II RAVENS trial is to evaluate the efficacy of MDT + radium-223 dichloride in prolonging progression free survival in men with HSOPCa. Methods Patients with HSOPCa and 3 or less metastases with at least 1 bone metastasis will be randomized 1:1 to stereotactic ablative radiation (SABR, also known as stereotactic body radiation therapy (SBRT)) alone vs SABR + radium-223 dichloride with a minimization algorithm to balance assignment by institution, primary intervention, prior hormonal therapy, and PSA doubling time. SABR is delivered in one to five fractions and patients in the SABR + radium-223 dichloride arm will receive six infusions of radium-223 dichloride at four-week intervals. The primary end point is progression free survival. The secondary clinical endpoints include toxicity and quality of life assessments, local control at 12 months, locoregional progression, time to distant progression, time to new metastasis, and duration of response. Discussion The RAVENS trial will be the first described phase II, non-blinded, randomized study to compare SABR +/− radium-223 dichloride in patients with HSOPCa and 3 or less metastases with at least one bone metastasis. The primary hypothesis is that SABR + radium-223 dichloride will increase median progression-free survival from 10 months in the SABR arm to 20 months in the SABR + radium-223 dichloride arm. Trial registrations Clinicaltrials.gov. Identifier: NCT04037358. Date of Registration: July 30, 2019. Date of First Participant Enrolled: August 9, 2019. Date of Last Approved Amendment: October 16, 2019. Protocol Version: Version 5.

A number of positron emission tomography (PET) radiotracers have been developed to improve the sensitivity and specificity of imaging for prostate cancer. These radiotracers include the bone-seeking agent Na18F as well as more tumor-specific compounds such as 11C-choline and 18F-fluciclovine. In this review, we will discuss the advantages and disadvantages of these PET radiotracers for the imaging of men with prostate cancer across a range of clinical contexts. We will also touch upon radiotracers in late clinical development that have not gained regulatory approval, including those targeted against prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR).

para-Aminobenzoic acid (PABA) has been previously used as an exogenous marker to verify completion of 24-h urine sampling. Therefore, we hypothesized that PABA radiolabeled with (11)C might allow high-quality dynamic PET of the kidneys with less radiation exposure than other agents because of its shorter biologic and physical half-life. We evaluated if (11)C-PABA can visualize renal anatomy and quantify function in healthy rats and rabbits and in a first-in-humans study on healthy volunteers. Methods: Healthy rats and rabbits were injected with (11)C-PABA intravenously. Subsequently, dynamic PET was performed, followed by postmortem tissue-biodistribution studies. (11)C-PABA PET was directly compared with the current standard, (99m)Tc-mercaptoacetyltriglycin, in rats. Three healthy human subjects also underwent dynamic PET after intravenous injection of (11)C-PABA. Results: In healthy rats and rabbits, dynamic PET demonstrated a rapid accumulation of (11)C-PABA in the renal cortex, followed by rapid excretion through the pelvicalyceal system. In humans, (11)C-PABA PET was safe and well tolerated. There were no adverse or clinically detectable pharmacologic effects in any subject. The cortex was delineated on PET, and the activity gradually transited to the medulla and then pelvis with high spatiotemporal resolution. Conclusion: (11)C-PABA demonstrated fast renal excretion with a very low background signal in animals and humans. These results suggest that (11)C-PABA might be used as a novel radiotracer for functional renal imaging, providing high-quality spatiotemporal images with low radiation exposure.

Purpose: Stereotactic ablative radiation therapy (SABR) for oligometastatic prostate cancer (OMPC) may improve clinical outcomes, but current challenges in intrafraction tracking of multiple small targets limits treatment accuracy. A biology-guided radiation therapy (BgRT) delivery system incorporating positron emission tomography (PET) detectors is being developed to use radiotracer uptake as a biologic fiducial for intrafraction tumor tracking to improve geometric accuracy. This study simulates prostate-specific membrane antigen (PSMA)-directed BgRT using a cohort from our phase II randomized trial of SABR in men with recurrent hormone sensitive OMPC and compares dose distributions to clinical SABR (CSABR). Methods and Materials: A research treatment planning system (RTPS) was used to replan 15 patients imaged with PSMA-targeted 18F-DCFPyL PET/computed tomography and previously treated with CSABR using conventional linear accelerators (linacs). The RTPS models a prototype ring-mounted linac incorporating PET and kilo-voltage computed tomography imaging subsystems and can be used to optimize BgRT plans, as well as research SABR (RSABR) plans, which use the prototype linac without radiotracer guidance. CSABR, RSABR, and BgRT plans were compared in terms of maximum planning target volume (PTV) dose (Dmax), mean dose to proximal organs at risk (DOAR), conformity index, as well as voxel-wise correlation of dose with PET specific uptake values to investigate possible dose-painting effects. Results: RSABR and BgRT plans resulted in mean ± standard deviation increases in Dmax of 4 ± 11% (P = .21) and 18 ± 15% (P < .001) and reductions in DOAR of –20 ± 19% (P

Current rifampin dosing achieves subtherapeutic concentrations within S. aureus –infected bone, which can be overcome with higher rifampin dosing.

A 73-year-old man with history of grade group 1/Gleason 3 + 3 = 6 prostate adenocarcinoma status post prostatectomy had subsequent biochemical recurrence with serum prostate-specific antigen level of 2.4 ng/mL. He underwent an 18F-fluciclovine PET/CT scan that demonstrated a left prostate bed recurrence and an incidental 18F-fluciclovine-avid smooth-edged solitary lung nodule with internal fat attenuation. Such uptake of 18F-fluciclovine in a lung hamartoma could be mistaken for prostate cancer metastasis. Given the increasing use of advanced imaging for prostate cancer, there is need for the imaging specialist to know about pitfalls and how to interpret them.

INTRODUCTION AND OBJECTIVE:Several PSMA-targeted imaging agents are currently in development for initial staging of men at risk of harboring metastatic prostate cancer (PCa) not detected by convent...

The role of PET imaging with 11C-choline and 18F-fluciclovine in evaluating patients with prostate cancer (PCa) has become more important over the years and has been incorporated into the NCCN guidelines. A new generation of PET radiotracers targeting the prostate-specific membrane antigen (PSMA) is widely used outside the United States to evaluate patients with primary PCa and PCa recurrence. PET imaging influences treatment planning and demonstrates a significantly higher disease detection rate than conventional imaging such as computed tomography and MR imaging. Early data indicate that using PET radiotracers such as 18F-fluciclovine and PSMA improves patient outcomes. 68-Ga-PSMA-11 and 18F-DCFPyL-PET/CT were recently approved by the US Food & Drug Administration (FDA) for clinical use. Other PSMA radiotracers, including fluorinated variants, will likely gain FDA approval in the not-too-distant future.

OBJECTIVE. Theranostics have shown great promise for delivering precision medicine, particularly in neuroendocrine tumors (NETs). The clinical applications of radiolabeled somatostatin analogues in imaging and radionuclide therapy have been rapidly increasing over the past 2 decades and are currently integrated into the management guidelines of NETs. This article summarizes the available literature on different somatostatin receptor-targeting radiopharmaceuticals with theranostic potential in NETs, pheochromocytomas, and paragangliomas. We discuss the clinical application, administration, and toxicity of recent FDA-approved radionuclide therapies, including 177Lu-DOTATATE in advanced gastroenteropancreatic NETs and 131I-MIBG in advanced paragangliomas and pheochromocytomas. CONCLUSION. Several studies support the safety and clinical efficacy of peptide receptor radionuclide therapies in disease control and quality-of-life improvement in patients with NETs and report potential benefits of combined radionuclide treatment approaches. The utility and pitfalls of functional imaging in therapy response assessment and surveillance of NETs remain to be established.

Quantitative imaging biomarkers are widely used in PET for both research and clinical applications, yet bias in the underlying image data has not been well characterized. In the absence of a readily available reference standard for in vivo quantification, bias in PET images has been inferred using physical phantoms, even though arrangements of this sort provide only a poor approximation of the imaging environment in real patient examinations. In this study, we used data acquired from patient volunteers to assess PET quantitative bias in vivo. Image-derived radioactivity concentrations in the descending aorta were compared with blood samples counted on a calibrated γ-counter. Methods: Ten patients with prostate cancer were studied using 2-(3-(1-carboxy-5-[(6-(18)F-fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid PET/CT. For each patient, 3 whole-body PET/CT image series were acquired after a single administration of the radiotracer: shortly after injection as well as approximately 1 and 4 h later. Venous blood samples were obtained at 8 time points over an 8-h period, and whole blood was counted on a NaI γ-counter. A 10-mm-diameter, 20-mm-long cylindric volume of interest was positioned in the descending thoracic aorta to estimate the PET-derived radioactivity concentration in blood. A triexponential function was fit to the γ-counter blood data and used to estimate the radioactivity concentration at the time of each PET acquisition. Results: The PET-derived and γ-counter–derived radioactivity concentrations were linearly related, with an R (2) of 0.985, over a range of relevant radioactivity concentrations. The mean difference between the PET and γ-counter data was 4.8% ± 8.6%, with the PET measurements tending to be greater. Conclusion: Human image data acquired on a conventional whole-body PET/CT system with a typical clinical protocol differed by an average of around 5% from blood samples counted on a calibrated γ-counter. This bias may be partly attributable to residual uncorrected scatter or attenuation correction error. These data offer an opportunity for the assessment of PET bias in vivo and provide additional support for the use of quantitative imaging biomarkers.

Rationale The development of consensus guidelines for interpretation of Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is needed to provide more consistent reports in clinical practice. The standardization of PSMA-PET interpretation may also contribute to increasing the data reproducibility within clinical trials. Finally, guidelines in PSMA-PET interpretation are needed to communicate the exact location of findings to referring physicians, to support clinician therapeutic management decisions. Methods A panel of worldwide experts in PSMA-PET was established. Panelists were selected based on their expertise and publication record in the diagnosis or treatment of PCa, in their involvement in clinical guidelines and according to their expertise in the clinical application of radiolabeled PSMA inhibitors. Panelists were actively involved in all stages of a modified, nonanonymous, Delphi consensus process. Results According to the findings obtained by modified Delphi consensus process, panelist recommendations were implemented in a structured report for PSMA-PET. Conclusions The E-PSMA standardized reporting guidelines, a document supported by the European Association of Nuclear Medicine (EANM), provide consensus statements among a panel of experts in PSMA-PET imaging, to develop a structured report for PSMA-PET in prostate cancer and to harmonize diagnostic interpretation criteria.

Artificial intelligence (AI) has been widely applied to medical imaging. The use of AI for emission computed tomography, particularly single-photon emission computed tomography (SPECT) emerged nearly 30 years ago but has been accelerated in recent years due to the development of AI technology. In this review, we will describe and discuss the progress of AI technology in SPECT imaging. The applications of AI are dispersed in disease prediction and diagnosis, post-reconstruction image denoising, attenuation map generation, and image reconstruction. These applications are relevant to many disease categories such as the neurological disorders, kidney failure, cancer, heart disease, etc. This review summarizes these applications so that SPECT researchers can have a reference overview of the role of AI in current SPECT studies. For each application, we followed the timeline to present the evolution of AI's usage and offered insights on how AI was combined with the knowledge of underlying physics as well as traditional non-learning techniques. Ultimately, AI applications are critical to the progress of modern SPECT technology because they provide compensations for many deficiencies in conventional SPECT imaging methods and demonstrate unparalleled success. Nonetheless, AI also has its own challenges and limitations in the medical field, including SPECT imaging. These fundamental questions are discussed, and possible future directions and countermeasures are suggested.

Enterobacterales represent the largest group of bacterial pathogens in humans and are responsible for severe, deep-seated infections, often resulting in sepsis or death. They are also a prominent cause of multidrug-resistant (MDR) infections, and some species are recognized as biothreat pathogens. Tools for noninvasive, whole-body analysis that can localize a pathogen with specificity are needed, but no such technology currently exists. We previously demonstrated that positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-d-sorbitol (18F-FDS) can selectively detect Enterobacterales infections in murine models. Here, we demonstrate that uptake of 18F-FDS by bacteria occurs via a metabolically conserved sorbitol-specific pathway with rapid in vitro 18F-FDS uptake noted in clinical strains, including MDR isolates. Whole-body 18F-FDS PET/computerized tomography (CT) in 26 prospectively enrolled patients with either microbiologically confirmed Enterobacterales infection or other pathologies demonstrated that 18F-FDS PET/CT was safe, could rapidly detect and localize Enterobacterales infections due to drug-susceptible or MDR strains, and differentiated them from sterile inflammation or cancerous lesions. Repeat imaging in the same patients monitored antibiotic efficacy with decreases in PET signal correlating with clinical improvement. To facilitate the use of 18F-FDS, we developed a self-contained, solid-phase cartridge to rapidly (

Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals are playing a large role at the time of initial staging and biochemical recurrence for localizing prostate cancer, as well as in other emerging clinical settings. PSMA PET has demonstrated increased detection rate compared with conventional imaging and has been shown to change management plans in a substantial percentage of cases. The aims of this narrative review are to highlight the development and clinical impact of PSMA PET radiopharmaceuticals, to compare PSMA to other agents such as fluorine 18 fluciclovine and carbon 11 choline, and to highlight some of the individual PSMA PET agents that have contributed to the advancement of prostate cancer imaging.

Purpose: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is emerging as an important modality for imaging patients with prostate cancer (PCa). As with any imaging modality, indeterminate findings will arise. The PSMA reporting and data system (PSMA-RADS) version 1.0 codifies indeterminate soft tissue findings with the PSMA-RADS-3A moniker. We investigated the role of point-spread function (PSF) reconstructions on categorization of PSMA-RADS-3A lesions. Methods: This was a post hoc analysis of an institutional review board approved prospective trial. Around 60 min after the administration of 333 MBq (9 mCi) of PSMA-targeted 18F-DCFPyL, patients underwent PET/computed tomography (CT) acquisitions from the mid-thighs to the skull vertex. The PET data were reconstructed with and without PSF. Scans were categorized according to PSMA-RADS version 1.0, and all PSMA-RADS-3A lesions on non-PSF images were re-evaluated to determine if any could be re-categorized as PSMA-RADS-4. The maximum standardized uptake values (SUVs) of the lesions, mean SUVs of blood pool, and the ratios of those values were determined. Results: A total of 171 PSMA-RADS-3A lesions were identified in 30 patients for whom both PSF reconstructions and cross-sectional imaging follow-up were available. A total of 13/171 (7.6%) were re-categorized as PSMA-RADS-4 lesions with PSF reconstructions. A total of 112/171 (65.5%) were found on follow-up to be true positive for PCa, with all 13 of the re-categorized lesions being true positive on follow-up. The lesions that were re-categorized trended towards having higher SUVmax-lesion and SUVmax-lesion/SUVmean-blood-pool metrics, although these relationships were not statistically significant. Conclusions: The use of PSF reconstructions for 18F-DCFPyL PET can allow the appropriate re-categorization of a small number of indeterminate PSMA-RADS-3A soft tissue lesions as more definitive PSMA-RADS-4 lesions. The routine use of PSF reconstructions for PSMA-targeted PET may be of value at those sites that utilize this technology.

Bone metastases in prostate cancer (PCa) have important prognostic significance, and imaging modalities used for PCa staging should have high sensitivity for detecting such lesions. Prostate-specific membrane antigen (PSMA)-targeted PET radiotracers are promising new agents for imaging PCa. We undertook a head-to-head comparison of PSMA-targeted 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) PET to Na18F PET to determine which modality was more sensitive for the detection of lesions suggestive of bone metastases in a group of patients with metastatic PCa. Methods: Patients with progressive, metastatic PCa were prospectively imaged with both 18F-DCFPyL and Na18F PET/CT, with both scans occurring within 24 h of each other. A consensus 2-reader central review was performed to identify all bone lesions suggestive of sites of PCa involvement on both scans, and maximized SUVs corrected for body weight (SUVmax) and lean body mass (SULmax) were recorded. Soft-tissue lesions were also noted on both scans, and SUVmax, SULmax, and PSMA reporting and data system (RADS) version 1.0 scores were recorded. Data from the 2 scans were compared using a generalized estimating equation. Results: In total, 16 patients meeting all inclusion criteria were enrolled in this study, and 15 of the 16 (93.8%) were imaged with both PET radiotracers. In total, 405 bone lesions suggestive of sites of PCa were identified on at least 1 scan. On 18F-DCFPyL PET/CT, 391 (96.5%) were definitively positive, 4 (1.0%) were equivocally positive, and 10 (2.5%) were negative. On Na18F PET/CT, the corresponding values were 388 (95.8%), 4 (1.0%), and 13 (3.2%). Of the definitively negative lesions on 18F-DCFPyL PET, 8 of 10 (80.0%) were sclerotic and 2 of 10 (20.0%) were infiltrative or marrow-based. Additionally, 12 of 13 (92.3%) of the definitively negative lesions on Na18F PET were infiltrative or marrow-based and 1 of 13 (7.7%) was lytic. Also identified were 78 PSMA-RADS-4, 17 PSMA-RADS-5, and 1 PSMA-RADS-3C soft-tissue lesions. Conclusion: PET/CT imaging using 18F-DCFPyL and Na18F PET had nearly identical sensitivities for the detection of bone lesions in patients with metastatic PCa. As would be expected, PSMA-targeted PET provides more information on soft-tissue disease. There may be little additional value to imaging PCa patients with Na18F after a PSMA-targeted PET scan has already been performed.

Emerging evidence supports a hypothesized role for the α7-nicotinic acetylcholine receptor (α7-nAChR) in the pathophysiology of Alzheimer's disease. 18F-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-18F-fluorodibenzo[b,d]thiophene 5,5-dioxide) is a radioligand for estimating the availability of α7-nAChR in the brain in vivo with PET. Methods: In this cross-sectional study, 14 patients with mild cognitive impairment (MCI), a prodromal stage to dementia, and 17 cognitively intact, elderly controls completed 18F-ASEM PET. For each participant, binding in each region of interest was estimated using Logan graphical analysis with a metabolite-corrected arterial input function. Results: Higher 18F-ASEM binding was observed in MCI patients than in controls across all regions, supporting higher availability of α7-nAChR in MCI. 18F-ASEM binding was not associated with verbal memory in this small MCI sample. Conclusion: These data support use of 18F-ASEM PET to examine further the relationship between α7-nAChR availability and MCI.

Purpose Taking full advantage of positron emission tomography (PET) technology, fluorine-18-labelled radiotracers targeting norepinephrine transporter (NET) have potential applications in the diagnosis and assessment of cardiac sympathetic nerve conditions as well as the delineation of neuroendocrine tumours. However, to date, none have been used clinically. Drawbacks of currently reported radiotracers include suboptimal kinetics and challenging radiolabelling procedures. Procedures We developed a novel fluorine-18-labelled radiotracer targeting NET, AF78, with efficient one-step radiolabelling based on the phenethylguanidine structure. Radiosynthesis of AF78 was undertaken, followed by validation in cell uptake studies, autoradiography, and in vivo imaging in rats. Results [18F]AF78 was successfully synthesized with 27.9 ± 3.1 % radiochemical yield, > 97 % radiochemical purity and > 53.8 GBq/mmol molar activity. Cell uptake studies demonstrated essentially identical affinity for NET as norepinephrine and meta-iodobenzylgaunidine. Both ex vivo autoradiography and in vivo imaging in rats showed homogeneous and specific cardiac uptake. Conclusions The new PET radiotracer [18F]AF78 demonstrated high affinity for NET and favourable biodistribution in rats. A structure-activity relationship between radiotracer structures and affinity for NET was revealed, which may serve as the basis for the further design of NET targeting radiotracers with favourable features. Electronic supplementary material The online version of this article (10.1007/s11307-019-01407-5) contains supplementary material, which is available to authorized users.

The continuing adoption of prostate specific membrane antigen (PSMA)-targeted PET for prostate cancer molecular imaging requires imagers and clinicians alike to be aware of the increasing number of potential interpretive pitfalls that have been reported. This review summarizes and illustrates the spectrum of benign and malignant nonprostatic conditions with high PSMA-radiotracer uptake that may be mistaken for sites of prostate cancer and also discusses potential false negatives. We discuss the recent literature on the effect of androgen deprivation therapy on lesion detection. Furthermore, we briefly review the recently proposed structured reporting systems for the standardized interpretation of PSMA-targeted PET that can guide both imaging specialists and referring clinicians in the appropriate interpretation and work-up of pitfalls.