Search

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.

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.

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.

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.

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.

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.

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

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.

Extensive research is currently being conducted into dynamic positron emission tomography (PET) acquisitions (including dynamic whole-body imaging) as well as extraction of radiomic features from imaging modalities. We describe a new PET viewing software known as Imager-4D that provides a facile means of viewing and analyzing dynamic PET data and obtaining associated quantitative metrics including radiomic parameters. The Imager-4D was programmed in the Java language utilizing the FX extensions. It is executable on any system for which a Java w/FX compliant virtual machine is available. The software incorporates the ability to view and analyze dynamic data acquired with different types of dynamic protocols. For image display, the program maintains a built-in library of 62 different lookup tables with monochromatic and full-color distributions. The Imager-4D provides multiple display layouts and can display fused images. Multiple methods of volume-of-interest (VOI) selection are available. Dynamic analysis features, such as image summation and full Patlak analysis, are also available. The user interface includes window width and level, blending, and zoom functionality. VOI sizes are adjustable and data from VOIs can either be displayed numerically or graphically within the software or exported. An example case of a 50-year-old woman with metastatic colorectal cancer and thyroiditis is included and demonstrates the steps for a user to obtain standard PET parameters, dynamic data, and radiomic features using selected VOIs. The Imager-4D represents a novel PET viewer that allows the user to view dynamic PET data, to derive dynamic and radiomic parameters from that data, and to combine dynamic data with radiomics (“dynomics”). The Imager-4D is available as a free download. This software has the potential to speed the adoption of advanced analysis of dynamic PET data into routine clinical use.

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.

Our purpose is to provide the results of a prospective study evaluating prostate-specific membrane antigen–targeted (18)F-DCFPyL (2-(3-{1-carboxy-5-[(6-(18)F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) PET/CT in patients with biochemical failure after radical prostatectomy for prostate cancer (PCa). Methods: Thirty-one patients with postprostatectomy serum prostate-specific antigen (PSA) levels of at least 0.2 ng/mL and negative conventional imaging results were enrolled in this study and imaged with (18)F-DCFPyL PET/CT. A consensus central review identified foci of radiotracer uptake consistent with sites of PCa. Descriptive statistics were used. Results: Twenty-one patients (67.7%) had at least 1 finding on (18)F-DCFPyL PET/CT consistent with a site of PCa. Imaging was positive in 59.1% of patients with a PSA level of less than 1.0 ng/mL and in 88.9% of patients with a PSA level of more than 1.0 ng/mL. The median SUV(max) across all lesions was 11.6 (range, 1.5–57.6). Conclusion: In this prospective study using the prostate-specific membrane antigen–targeted PET agent (18)F-DCFPyL, most patients with biochemical failure after radical prostatectomy had foci of suggestive uptake, even at low serum PSA levels.

Complete surgical resection of metastatic sites has been shown to prolong survival in select patients with oligometastatic RCC. This treatment strategy is dependent upon the accurate characterization of a patient’s extent of disease. The objective of this study was to explore the utility of PSMA-targeted 18F-DCFPyL PET/CT in patients with presumed oligometastatic clear cell RCC. This is a subset analysis of a prospective study in which patients with RCC were imaged with 18F-DCFPyL PET/CT (ClinicalTrials.gov identifier NCT02687139). In the present analysis, patients with oligometastatic clear cell RCC, defined as ≤ 3 metastatic lesions on conventional imaging, were evaluated. 18F-DCFPyL PET/CT scans were reviewed for sites of disease and compared to conventional imaging. The final cohort included 14 patients with oligometastatic clear cell RCC. Conventional imaging revealed 21 metastatic lesions and 3 primary tumors. 18F-DCFPyL PET/CT detected 29 sites of metastatic disease and 3 primary tumors. Of the 21 metastatic lesions detected on conventional imaging, 17 (81.0%) had radiotracer uptake. Additionally, all 3 primary tumors had radiotracer uptake. In 4 (28.6%) patients a total of 12 more lesions were identified on 18F-DCFPyL PET/CT than conventional imaging. Notably, 3 (21.4%) patients were no longer considered oligometastatic. The detection rates of conventional imaging and 18F-DCFPyL PET/CT for identifying sites of disease were 66.7% and 88.9%, respectively. PSMA-targeted PET/CT appears to aid in the identification of patients with oligometastatic clear cell RCC. If borne out in future studies, this suggests that PSMA-targeted imaging has the potential to help select candidates for metastasis-directed therapy.

PURPOSE: In this study, we aimed to quantitatively investigate the biodistribution of [(18)F]DCFPyL in patients with prostate cancer (PCa) and to determine whether uptake in normal organs correlates with an increase in tumor burden. PROCEDURES: 50 patients who had been imaged with [(18)F]DCFPyL positron emission tomography/computed tomography (PET/CT) were retrospectively included in this study. 40/50 (80%) demonstrated radiotracer uptake on [(18)F]DCFPyL PET/CT compatible with sites of PCa. Volumes of Interests (VOI) were set on normal organs (lacrimal glands, parotid glands, submandibular glands, liver, spleen, and kidneys) and on tumor lesions. Mean standardized uptake values corrected to lean body mass (SUL(mean)) and mean standardized uptake values corrected to body weight (SUV(mean)) for normal organs were assessed. For the entire tumor burden, SUL(mean/max), SUV(mean), tumor volume (TV), and the total activity in the VOI were obtained using tumor segmentation. A Spearman’s rank correlation coefficient was used to investigate correlations between normal organ uptake and tumor burden. RESULTS: There was no significant correlation between TV with the vast majority of the investigated organs (lacrimal glands, parotid glands, submandibular glands, spleen, and liver). Only the kidney showed significant correlation: With an isocontour threshold at 50%, left kidney uptake parameters correlated significantly with TV (SUV(mean), ρ = −0.214 and SUL(mean), ρ = −0.176, p < 0.05, respectively). CONCLUSIONS: Only a minimal sink effect with high tumor burden in patients imaged with [(18)F]DCFPyL was observed. Other factors, such as a high intra-patient variability of normal organ uptake, may be a much more important consideration for personalized dosimetry with PSMA-targeted therapeutic agents structurally related to [(18)F]DCFPyL than the tumor burden.

PURPOSE: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has impacted the management of patients with prostate cancer (PCa) in many parts of the world. PSMA-targeted endoradiotherapies are also being increasingly utilized and for these applications, the radiopharmaceutical distribution in normal organs is particularly important because it may limit the dose that can be delivered to tumors. In this study, we measured both interpatient and intrapatient variability of [(18)F]DCFPyL uptake in the most relevant normal organs. PROCEDURES: Baseline and 6-month follow-up PSMA-targeted [(18)F]DCFPyL PET/computed tomography (CT) scans from 39 patients with PCa were reviewed. Volumes of interest were manually drawn using the best visual approximation of the organ edge for both lacrimal glands, all four major salivary glands, the liver, the spleen, and both kidneys for all patients. The average SUV(mean), the COVs, and intraclass correlation coefficients (ICCs) across scans were calculated. Bland-Altman analyses were performed for all organs to derive repeatability coefficients (RCs). RESULTS: The liver demonstrated the lowest interpatient variability (13.0 and 16.6 % at baseline and follow-up, respectively), while the spleen demonstrated the largest interpatient variability (44.6 and 51.0 % at baseline and follow-up, respectively). The lowest intrapatient variability was found in the spleen (ICC 0.86) while the highest intrapatient variability was in the kidneys (ICCs 0.40–0.50). Bland-Altman analyses showed 95 % repeatability coefficients for mean uptake >40 % for multiple organs and were highest for the lacrimal glands, kidneys, and spleen. CONCLUSIONS: Normal organs demonstrate significant variability in uptake of the PSMA-targeted radiotracer [(18)F]DCFPyL. Depending on the organ, different contributions of interpatient and intrapatient factors affect the intrinsic variability. The RCs also vary significantly among the different organs were highest for the lacrimal glands, kidneys, and spleen. These findings may have important implications for the design of clinical protocols and personalized dosimetry for PSMA-targeted endoradiotherapies.

This meta-analysis aims to establish the diagnostic performance of 18F-NaF-PET/CT for the detection of bone metastases in prostate cancer patients. The performance of 18F-NaF-PET/CT was compared with other imaging techniques in the same cohort of patients. A systematic search was performed in PubMed/Medline and EMBASE (last Updated, September 28, 2018). Studies with histopathology confirmation and/or clinical/imaging follow-up as reference standard were eligible for inclusion. A total of 14 studies were included. Twelve studies including 507 patients provided per-patient basis information. The pooled sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the summary receiver operating characteristics curve (AUC) of 18F-NaF-PET/CT for the detection of bone metastases were 0.98 (95% CI 0.95–0.99), 0.90 (95% CI 0.86–0.93), 123.2 and 0.97, respectively. Seven studies provided the lesion-based accuracy information of 1812 lesions identified on 18F-NaF-PET/CT with the pooled sensitivity, specificity, DOR and AUC of 0.97 (95% CI 0.95–0.98), 0.84 (95% CI 0.81–0.87), 206.8 and 0.97, respectively. The overall diagnostic performance of 18F-NaF-PET/CT is superior to 99mTc-bone scintigraphy (AUC 0.842; P

In recent years, small-molecule inhibitors of prostate-specific membrane antigen (PSMA) labeled with radionuclides that allow for positron emission tomography (PET) imaging have been extensively studied in many clinical contexts in men with prostate cancer (PCa). The high sensitivity and specificity of these agents for identifying sites of PCa has quickly led to their widespread adoption as a de facto clinical standard of care throughout much of the world. PSMA-targeted PET radiotracers have been particularly well-studied in preoperatively staging men with high-risk PCa, evaluating biochemical recurrence following definitive therapy, and guiding metastasis-directed therapy in patients suspected of having oligorecurrent/oligometastatic disease. Furthermore, the expression of PSMA on the tumor neovasculature of many nonprostate malignancies has enabled a burgeoning subfield concentrated on delineating the potential utility of PSMA-targeted PET agents for imaging other cancers. In this review, we highlight the preclinical development of key small molecules that are now being clinically utilized for PCa imaging, discuss the roles of PSMA-targeted agents in guiding patient management, and consider the role these compounds may play in imaging nonprostate cancers.

Three-dimensional (3D) visualizations of computed tomography (CT) data have found use in the display of complex anatomy and pathology. A new method of 3D CT image creation known as cinematic rendering (CR) makes use of a global lighting model to produce photorealistic images. Cinematic rendering images contain high levels of detail with shadowing and depth that are not available from traditional 3D CT techniques. As yet, the role of CR in evaluating colonic pathology has not been investigated. However, given the breadth of pathologic processes that affect the colon, including inflammatory bowel disease, diverticulitis, neoplastic conditions, herniation, and gastrointestinal bleeding, we undertook a survey of recent cases at our institution to demonstrate colon pathology as visualized with CR. The following review discusses the role of 3D CT visualizations for colonic pathology with an emphasis on CR example images.

New radiotracers for positron emission tomography imaging that target prostate-specific membrane antigen (PSMA) have emerged as important clinical tools for imaging prostate cancer (PCa). PSMA-targeted radiotracers have demonstrated high sensitivity and high specificity for detecting sites of PCa and are demonstrably superior to conventional imaging modalities such as computed tomography and bone scan. Vas deferens invasion is a rarely encountered poor prognostic feature of PCa. In this case report, we describe a novel pattern of radiotracer uptake in a patient with PCa imaged with PSMA-targeted 18F-DCFPyL positron emission tomography/computed tomography that is consistent with diffuse vas deferens involvement.

In recent years, the emergence of prostate-specific membrane antigen (PSMA)-targeted positron-emission tomography (PET) imaging has brought about a paradigm shift in the way that prostate cancer (PCa) is imaged in many parts of the world. Although PSMA-targeted PET imaging has been demonstrated to be a highly sensitive and specific imaging modality for the identification of sites of PCa, its clinical utility hinges on the ability of imaging specialists and their clinical colleagues to recognize potential false-positive sources of uptake and to tailor therapy based on that recognition. In this manuscript, we report the case of a 74-year-old male with a history of recurrent PCa who was referred for a restaging PSMA-targeted 18F-DCFPyL PET/computed tomography (PET/CT). PET images demonstrated low level but focal and definitive uptake in the left femoral head. This uptake corresponded to sclerotic changes on CT whose morphology was most compatible with avascular necrosis without femoral head collapse. In the presented case, the integrated assessment of the CT imaging together with the PET findings was fundamental to avoid misinterpretation of the left femur finding as metastatic disease, which would have ultimately altered the clinical management of the patient.

Even as medical data sets become more publicly accessible, most are restricted to specific medical conditions. Thus, data collection for machine learning approaches remains challenging, and synthetic data augmentation, such as generative adversarial networks (GAN), may overcome this hurdle. In the present quality control study, deep convolutional GAN (DCGAN)–based human brain magnetic resonance (MR) images were validated by blinded radiologists. In total, 96 T1-weighted brain images from 30 healthy individuals and 33 patients with cerebrovascular accident were included. A training data set was generated from the T1-weighted images and DCGAN was applied to generate additional artificial brain images. The likelihood that images were DCGAN-created versus acquired was evaluated by 5 radiologists (2 neuroradiologists [NRs], vs 3 non-neuroradiologists [NNRs]) in a binary fashion to identify real vs created images. Images were selected randomly from the data set (variation of created images, 40%–60%). None of the investigated images was rated as unknown. Of the created images, the NRs rated 45% and 71% as real magnetic resonance imaging images (NNRs, 24%, 40%, and 44%). In contradistinction, 44% and 70% of the real images were rated as generated images by NRs (NNRs, 10%, 17%, and 27%). The accuracy for the NRs was 0.55 and 0.30 (NNRs, 0.83, 0.72, and 0.64). DCGAN-created brain MR images are similar enough to acquired MR images so as to be indistinguishable in some cases. Such an artificial intelligence algorithm may contribute to synthetic data augmentation for “data-hungry” technologies, such as supervised machine learning approaches, in various clinical applications.

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.

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.

We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer 68Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard 18F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent 18F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. 68Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while18F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, 18F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to 68Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard 18F-FDG PET/CT.

PurposeDevelop a 64Cu labeled radiopharmaceutical targeting prostate specific membrane antigen (PSMA) and investigate its application for prostate cancer imaging. Methods64Cu-PSMA-BCH was prepared and investigated for stability, PSMA specificity and micro-PET imaging. With the approval of Ethics Committee of Beijing Cancer Hospital (No. 2017KT97), PET/CT imaging in 4 patients with suspected prostate cancer was performed and the radiation dosimetry was estimated. Then, PSMA PET-ultrasound image-guided biopsies were performed on 3 patients and the fine needle aspirates were further performed for autoradiography and immunohistochemistry analysis. Results64Cu-PSMA-BCH was prepared with high radiochemical yield and stability. In vivo study showed higher uptake in PSMA (+) 22Rv1 cells than PSMA (-) PC-3 cells (5.59±0.36 and 1.97±0.22 IA%/106 cells at 1 h). It accumulated in 22Rv1 tumor with increasing radioactivity uptake and T/N ratios from 1 h to 24 h post-injection. In patients with suspected prostate cancer, SUVmax and T/N ratios increased within 24 h post-injection. Compared with image at 1 h post-injection, more tumor lesions were detected at 4 h and 24 h post-injection. The human organ radiation dosimetry showed gallbladder wall was most critical, liver and kidneys were followed, and the whole-body effective dose was 0.0292 mSv/MBq. Two fine needle aspirates obtained by PET-ultrasound guided targeted biopsy showed high radioactive signal by autoradiography, with 100% PSMA expression in cytoplasm and 30% expression in nucleus. Conclusion64Cu-PSMA-BCH was PSMA specific and showed high stability in vivo with lower uptake in liver than 64Cu-PSMA-617. Biodistribution in mice and PCa patients showed similar profile compared with other PSMA ligands and it was safe with moderate effective dosimetry. The increased tumor uptake and T/N ratios by delayed imaging may facilitate the detection of small lesions and guiding targeted biopsies.

Soluble epoxide hydrolase (sEH) is an enzyme with putative effect on neuroinflammation through its influence on the homeostasis of polyunsaturated fatty acids and related biproducts. Since sEH is an enzyme that metabolizes the anti-inflammatory epoxy fatty acids to relatively inert 1,2-diol forms, a high availability or activity of sEH may promote vasoconstriction and inflammation in local tissues that may be linked to neuropsychiatric disease such as depressive disorders. [(18)F]FNDP is a radiotracer developed by our group for studying sEH in the living human brain with positron emission tomography (PET). METHODS: Brain PET using bolus injection of [(18)F]FNDP followed by emission imaging lasting 90 or 180 min was completed in seven healthy adults (5 males, 2 females, ages 40–53 years). The kinetic behavior of [(18)F]FNDP was evaluated using a metabolite corrected arterial plasma input function with compartmental or graphical modeling approaches. RESULTS: [(18)F]FNDP PET was well tolerated. Akaike information criterion favored the two-tissue compartment model (2TCM) in all ten regions of interest. Regional total distribution volume (V(T)) values from each compartmental model and Logan analysis were generally well-identified except corpus callosum V(T) using 2TCM. Logan analysis was assessed as the choice model due to stability of the regional V(T) values from 90 min data and due to high correlation of Logan-derived regional V(T) values with those from the 2TCM. The distribution of sEH differed from that of our prior study of primate brain, with higher binding in human cerebellar cortex and thalamus relative to other cortical regions, which aligns with reported consensus expression patterns of the epoxide hydrolase 2 gene in human brain. CONCLUSION: These data support further use of [(18)F]FNDP PET to study sEH in human brain.

Tracing its roots back to the 1940s, theranostics in nuclear oncology has proved successful mainly due to the beneficial effects of image-guided therapeutic concepts for patients afflicted with a variety of different cancers. The majority of these treatments are not only characterized by substantial prolongation of progression-free and overall survival, but are also generally safe, rendering theranostic agents as an attractive treatment option in various clinical scenarios in oncology. In this Special Issue Novel Theranostic Agents, nine original articles from around the globe provide further evidence on the use of the theranostic concept for neuroendocrine neoplasm (NEN), prostate cancer (PC), meningioma, and neuroblastoma. The investigated diagnostic and therapeutic radiotracers target not only established structures, such as somatostatin receptor, prostate-specific membrane antigen or norepinephrine transporter, but also recently emerging targets such as the C-X-C motif chemokine receptor 4. Moreover, the presented original articles also combine the concept of theranostics with in-depth read-out techniques such as radiomics or novel reconstruction algorithms on pretherapeutic scans, e.g., for outcome prediction. Even 80 years after its initial clinical introduction, theranostics in oncology continues to thrive, now more than ever.

Prostate-specific membrane antigen (PSMA; also termed glutamate carboxypeptidase II (GCP II)) is abundantly expressed in prostate cancer. It has been shown recently that PSMA is expressed in neovasculature of differentiated thyroid cancer. In this study, we show that 18F-DCFPyl might detect neovasculature in advanced, metastatic differentiated thyroid cancer (DTC). We first stained the preserved lymph node samples of three patients with DTC who had undergone total thyroidectomy and neck dissection for cervical lymph node metastatic disease to identify PSMA expression, with the PSMA antibody (DAKO Monoclonal). Then, we performed 18F-DCFPyl imaging in two other advanced DTC patients with elevated serum thyroglobulin (Tg), indicative of residual disease. We compared the findings with contemporaneous FDG PET/CT scan, conventional Imaging (CT,MRI) and whole-body scan performed with I123/I131. All the three lymph node samples stained positive for PSMA expression in the neovasculature. In the first imaged patient, 18F-DCFPyl detected activity within the retropharyngeal CT contrast-enhancing lymph node. Compared to FDG PET/CT, the 18F-DCFPyl scan showed a greater SUV (3.1 vs 1.8). In the second imaged patient, 18F-DCFPyl showed intense uptake in the L3 vertebra (not seen on the post treatment 131I scan or the 18F-FDG PET/CT). MRI of the lumbar spine confirmed the presence of sclerotic-lytic lesion at the location, consistent with metastatic disease. Our exploratory study is proof of principle, that the prostate cancer imaging agent 18F-DCFPyl may prove useful for the localization of metastases, in patients with metastatic RAI-refractory DTC by detecting neoangiogenesis within the tumor.

To prospectively evaluate the distribution of PSMA-targeted PET-avid lesions in prostate cancer (PCa) patients with biochemical recurrence in a Chinese cohort. The relationships between PSA levels, disease-free time after prostatectomy, and 68Ga-PSMA-11 PET/computed tomography (CT) findings were investigated. Inclusion criteria included histopathologically proven prostate adenocarcinoma, two consecutive PSA levels > 0.20 ng/mL, and negative CT of the abdomen and pelvis or magnetic resonance imaging of the pelvis and whole-body bone scan. Exclusion criteria were non-prostate malignancy within 3 years and persistent PSA after radical prostatectomy. Patients with findings of recurrent disease on re-staging conventional imaging were excluded, as were patients previously treated with systemic therapy and/or salvage therapy. 51 patients were enrolled in this study. 34/51 (66.7%) patients had at least one site of 68Ga-PSMA-11 uptake consistent with PCa. 23.5% of patients had recurrence in the prostate bed, 27.4% had pelvic lymph nodes, 15.7% had extrapelvic lymph node metastases, and 17.6% had bone metastases. For patients with lymph node involvement/metastasis, bone metastasis, and patients with both, their median serum PSA levels were 1.83 ng/mL, 4.03 ng/mL, and 2.54 ng/mL, respectively. They were diagnosed with recurrence with a median of 2.06 years, 1.15 years, and 2.54 years after radical prostatectomy, respectively. In this study of Chinese men with biochemical recurrence, added value for the detection of lesions compatible with sites of PCa was found with 68Ga-PSMA-11 PET/CT over conventional imaging. The observed patterns of disease spread may have implications for understanding the biology of early prostate cancer metastasis.

The purpose of this study was to investigate the feasibility and diagnostic efficacy of (68)Ga-prostate-specific membrane antigen (PSMA) PET/CT combined with PET/ultrasound-guided biopsy in the diagnosis of prostate cancer (PCa). Methods: In total, 31 patients with a previously negative prostate biopsy but persistent elevated serum prostate-specific antigen (PSA) were imaged with a (68)Ga-PSMA PET/CT ligand before undergoing repeat prostate biopsy. On the basis of the proposed Prostate Cancer Molecular Imaging Standardized Evaluation criteria, (68)Ga-PSMA PET/CT results were interpreted as negative (molecular-imaging-for-PSMA expression score [miPSMA-ES] of 0–1) or positive (miPSMA-ES of 2–3). All patients underwent standard template systematic biopsy with up to 4 additional PET/ultrasound-guided biopsy cores. The sensitivity, specificity, positive and negative predictive values, and accuracy of (68)Ga-PSMA PET/CT were determined. In addition, the correlation between the miPSMA-ES and the detection rate of PCa was also analyzed. Univariate logistic regression models were established using (68)Ga-PSMA PET/CT semiquantitative analysis parameters to predict the outcome of repeat prostate biopsy. Results: The median age of patients was 65 y (range, 53–81 y), and the median PSA level was 18.0 ng/mL (range, 5.48–49.77 ng/mL). PCa was detected in 15 of 31 patients (48.4%), and 12 of 31 patients (38.7%) had clinically significant PCa (csPCa). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of (68)Ga-PSMA PET/CT in the diagnosis of csPCa were 100.0%, 68.4%, 66.7%, 100.0%, and 80.6%, respectively. The detection rate of PCa increased with the increase in miPSMA-ES. The detection rates of csPCa in the miPSMA-ES 0–1, 2, and 3 groups were 0%, 54.5%, and 85.7%, respectively. Semiquantitative analysis of (68)Ga-PSMA PET/CT images showed that predictive models based on the SUV(max) of prostate lesion, tumor–to–normal-prostate background SUV(max), and tumor–to–normal-liver background SUV(max) could effectively predict csPCa; area under the curves were 0.930, 0.877, and 0.956, respectively. Conclusion: This study preliminarily confirmed that (68)Ga-PSMA PET/CT imaging, combined with PET/ultrasound-guided prostate biopsy, can effectively detect csPCa. Prebiopsy (68)Ga-PSMA PET/CT had predictive value for csPCa in the studied patient population.

Three-dimensional (3D) visualizations of volumetric data from computed tomography (CT) acquisitions can be important adjuncts to interpretation of two-dimensional (2D) reconstructions. Recently, the 3D technique known as cinematic rendering (CR) was introduced, allowing photorealistic images to be created from standard CT acquisitions. CR methodology is under increasing investigation for use in the display of regions of complex anatomy and as a tool for education and preoperative planning. In this article, we will illustrate the potential utility of CR for evaluating the urinary bladder and associated pathology. The urinary bladder is susceptible to a multitude of neoplastic and inflammatory conditions and their sequelae. The intrinsic properties of CR may prove useful for the display of subtle mucosal/luminal irregularities, the simultaneous display of soft tissue detail with high-resolution maps of associated tumor neovasculature, and the improved display of spatial relationships to aid pre-procedural planning. Further refinement of presets for CR image creation and prospective evaluation of urinary bladder CR in real-world settings will be important for widespread clinical adoption.

Clinician-scientists are commonly characterized as health care professionals who are proficient in both research and clinical practice. Their dual expertise positions them to play a vital role in translating research outcomes to clinical practice. However, economic changes in the past few decades are threatening their very survival. The purposes of this article are to review some of the economic forces that pose the greatest risks to clinician-scientists in the modern era and to glean lessons from the business world in overcoming these challenges. Health care consolidation and decreasing reimbursements are putting increasing financial pressure on academic institutions, leaving them more inclined to cut back on departmental research support. Innovative companies commit a certain percentage of their revenue to research and discovery. Academic institutions should similarly view their research budget as research and discovery that will sustain the future growth of radiology. They should quantify and define expectations for academic productivity, focus on return on investment, and bolster the infrastructure to foster commercial partnerships that can provide additional revenue to support the research mission. Success in academics does not occur by accident. It requires more than individual talent and hard work. It also requires institutional leaders who are committed to developing future academic leaders and supporting innovation.

To evaluate the outcomes of total eradication therapy (TET), designed to eradicate all sites of visible cancer and micrometastases, in men with newly diagnosed oligometastatic prostate cancer (OMPCa). Men with ≤ 5 sites of metastases were enrolled in a prospective registry study, underwent neoadjuvant chemohormonal therapy, followed by radical prostatectomy, adjuvant radiation (RT) to prostate bed/pelvis, stereotactic body radiation therapy (SBRT) to oligometastases, and adjuvant hormonal therapy (HT). When possible, the prostate-specific membrane antigen targeted 18F-DCFPyL PET/CT (18F-DCFPyL) scan was obtained, and abiraterone was added to neoadjuvant HT. Twelve men, median 55 years, ECOG 0, median PSA 14.7 ng/dL, clinical stages M0—1/12 (8%), M1a—3/12 (25%) and M1b—8/12 (67%), were treated. 18F-DCFPyL scan was utilized in 58% of cases. Therapies included prostatectomy 12/12 (100%), neoadjuvant [docetaxel 11/12 (92%), LHRH agonist 12/12 (100%), abiraterone + prednisone 6/12 (50%)], adjuvant radiation [RT 2/12 (17%), RT + SBRT 4/12 (33%), SBRT 6/12 (50%)], and LHRH agonist 12/12 (100%)]. 2/5 (40%) initial patients developed neutropenic fever (NF), while 0/6 (0%) subsequent patients given modified docetaxel dosing developed NF. Otherwise, TET resulted in no additive toxicities. Median follow-up was 48.8 months. Overall survival was 12/12 (100%). 1-, 2-, and 3-year undetectable PSA’s were 12/12 (100%), 10/12 (83%) and 8/12 (67%), respectively. Median time to biochemical recurrence was not reached. The outcomes suggest TET in men with newly diagnosed OMPCa is safe, does not appear to cause additive toxicities, and may result in an extended interval of undetectable PSA.