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Background Radioligand therapy (RLT) with 177Lu-labeled prostate-specific membrane antigen (PSMA) ligands is associated with prolonged overall survival (OS) in patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). A substantial number of patients, however, are prone to treatment failure. We aimed to determine clinical baseline characteristics to predict OS in patients receiving [177Lu]Lu-PSMA I&T RLT in a long-term follow-up. Materials and methods Ninety-two mCRPC patients treated with [177Lu]Lu-PSMA I&T with a follow-up of at least 18 months were retrospectively identified. Multivariable Cox regression analyses were performed for various baseline characteristics, including laboratory values, Gleason score, age, prior therapies, and time interval between initial diagnosis and first treatment cycle (intervalDiagnosis-RLT, per 12 months). Cutoff values for significant predictors were determined using receiver operating characteristic (ROC) analysis. ROC-derived thresholds were then applied to Kaplan–Meier analyses. Results Baseline C-reactive protein (CRP; hazard ratio [HR], 1.10, 95% CI 1.02–1.18; P = 0.01), lactate dehydrogenase (LDH; HR, 1.07, 95% CI 1.01–1.11; P = 0.01), aspartate aminotransferase (AST; HR, 1.16, 95% CI 1.06–1.26; P = 0.001), and intervalDiagnosis-RLT (HR, 0.95, 95% CI 0.91–0.99; P = 0.02) were identified as independent prognostic factors for OS. The following respective ROC-based thresholds were determined: CRP, 0.98 mg/dl (area under the curve [AUC], 0.80); LDH, 276.5 U/l (AUC, 0.83); AST, 26.95 U/l (AUC, 0.73); and intervalDiagnosis-RLT, 43.5 months (AUC, 0.68; P intervalDiagnosis-RLT (P ≤ 0.01, respectively). Conclusion In mCRPC patients treated with [177Lu]Lu-PSMA I&T, baseline CRP, LDH, AST, and time interval until RLT initiation (thereby reflecting a possible indicator for tumor aggressiveness) are independently associated with survival. Our findings are in line with previous findings on [177Lu]Lu-PSMA-617, and we believe that these clinical baseline characteristics may support the nuclear medicine specialist to identify long-term survivors.

Background CXCR4-directed positron emission tomography/computed tomography (PET/CT) has been used as a diagnostic tool in patients with solid tumors. We aimed to determine a potential correlation between tumor burden and radiotracer accumulation in normal organs. Methods Ninety patients with histologically proven solid cancers underwent CXCR4-targeted [68Ga]Ga-PentixaFor PET/CT. Volumes of interest (VOIs) were placed in normal organs (heart, liver, spleen, bone marrow, and kidneys) and tumor lesions. Mean standardized uptake values (SUVmean) for normal organs were determined. For CXCR4-positive tumor burden, maximum SUV (SUVmax), tumor volume (TV), and fractional tumor activity (FTA, defined as SUVmean x TV), were calculated. We used a Spearman's rank correlation coefficient (ρ) to derive correlative indices between normal organ uptake and tumor burden. Results Median SUVmean in unaffected organs was 5.2 for the spleen (range, 2.44 – 10.55), 3.27 for the kidneys (range, 1.52 – 17.4), followed by bone marrow (1.76, range, 0.84 – 3.98), heart (1.66, range, 0.88 – 2.89), and liver (1.28, range, 0.73 – 2.45). No significant correlation between SUVmax in tumor lesions (ρ ≤ 0.189, P ≥ 0.07), TV (ρ ≥ -0.204, P ≥ 0.06) or FTA (ρ ≥ -0.142, P ≥ 0.18) with the investigated organs was found. Conclusions In patients with solid tumors imaged with [68Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged.

Background Labelled with lutetium-177, the urea-based small molecules PSMA I&T and PSMA-617 are the two agents most frequently used for radioligand therapy (RLT) in patients with advanced metastatic castration-resistant and prostate-specific membrane antigen (PSMA) expressing prostate cancer (mCRPC). In this matched-pair analysis, we aimed to compare the toxicity and efficacy of both agents for PSMA-directed RLT. Materials and methods A total of 110 mCRPC patients from two centres were accrued, 55 individuals treated with [177Lu]Lu-PSMA I&T, and a matched cohort of 55 patients treated with [177Lu]Lu-PSMA-617. Matching criteria included age at the first cycle, Gleason score, prostate-specific antigen (PSA) values, and previous taxane-based chemotherapy. Using common terminology criteria for adverse events (CTCAE v. 5.0), toxicity profiles were investigated (including bone marrow and renal toxicity). Overall survival (OS) between both groups was compared. Results Toxicity assessment revealed grade III anaemia in a single patient (1.8%) for [177Lu]Lu-PSMA I&T and five (9.1%) for [177Lu]Lu-PSMA-617. In addition, one (1.9%) grade III thrombopenia for [177Lu]Lu-PSMA-617 was recorded. Apart from that, no other grade III/IV toxicities were present. A median OS of 12 months for patients treated with [177Lu]Lu-PSMA I&T did not differ significantly when compared to patients treated with [177Lu]Lu-PSMA-617 (median OS, 13 months; P = 0.89). Conclusion In this matched-pair analysis of patients receiving one of the two agents most frequently applied for PSMA RLT, the rate of clinically relevant toxicities was low for both compounds. In addition, no relevant differences for OS were observed.

Abstract Purpose For somatostatin receptor (SSTR)-positron emission tomography/computed tomography (PET/CT), a standardized framework termed SSTR-reporting and data system (RADS) has been proposed. We aimed to elucidate the impact of a RADS-focused training on reader’s anxiety to report on SSTR-PET/CT, the motivational beliefs in learning such a system, whether it increases reader’s confidence, and its implementation in clinical routine. Procedures A 3-day training course focusing on SSTR-RADS was conducted. Self-report questionnaires were handed out prior to the course (Pre) and thereafter (Post). The impact of the training on the following categories was evaluated: (1) test anxiety to report on SSTR-PET/CT, (2) motivational beliefs, (3) increase in reader’s confidence, and (4) clinical implementation. To assess the effect size of the course, Cohen’s d was calculated (small, d = 0.20; large effect, d = 0.80). Results Of 22 participants, Pre and Post were returned by 21/22 (95.5%). In total, 14/21 (66.7%) were considered inexperienced (IR, 1 year). Applying SSTR-RADS, a large decrease in anxiety to report on SSTR-PET/CT was noted for IR (d = − 0.74, P = 0.02), but not for ER (d = 0.11, P = 0.78). For the other three categories motivational beliefs, reader’s confidence, and clinical implementation, agreement rates were already high prior to the training and persisted throughout the course (P ≥ 0.21). Conclusions A framework-focused reader training can reduce anxiety to report on SSTR-PET/CTs, in particular for inexperienced readers. This may allow for a more widespread adoption of this system, e.g., in multicenter trials for better intra- and interindividual comparison of scan results.

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.

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

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.

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).

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.

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

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.

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.

PURPOSE: To investigate the utility of prostate-specific membrane antigen (PSMA)-targeted [(18)F]DCFPyL positron emission tomography (PET)/X-ray computed tomography (CT) imaging for the detection of sites of disease in patients with metastatic non-clear cell renal cell carcinoma (RCC). PROCEDURES: Eight patients with metastatic non-clear cell RCC underwent imaging with PSMA-targeted [(18)F]DCFPyL PET/CT. Imaged RCC histologic subtypes included papillary RCC (n = 3), chromophobe RCC (n = 2), unclassified RCC (n = 2), and Xp11 translocation RCC (n = 1). Using comparison to conventional CT and/or magnetic resonance imaging as reference, two radiologists with expertise in nuclear medicine identified putative sites of disease on [(18)F]DCFPyL PET/CT and classified each lesion as having no radiotracer uptake, equivocal uptake, or definitive uptake. RESUTS: In total, 73 metastatic sites and 3 primary tumors compatible with sites of non-clear cell RCC were identified on conventional imaging. Metastatic sites of disease included lymph nodes (n = 40), venous thrombi (n = 3), pulmonary nodules (n = 10), bone lesions (n = 15), brain lesions (n = 3), and retroperitoneal masses (n = 2). Only 10 of the 73 lesions (13.7 %) were classified as having definitive radiotracer uptake (median SUV(max) = 3.25, range = 1.2–9.5), 14 lesions (19.2 %) had equivocal uptake (median SUV(max) = 2.85, range = 0.5–6.5), and 49 lesions (67.1 %) had no definitive uptake above background (median SUV(max) = 1.7, range = 0.2–3.0). The three primary renal tumors demonstrated lower radiotracer avidity relative to surrounding normal renal parenchyma. CONCLUSIONS: A small proportion of sites of non-clear cell RCC showed uptake of the PSMA-targeted radiotracer [(18)F]DCFPyL. Unlike for clear cell RCC, the results of this study indicate that PSMA-based PET is not appropriate for imaging other RCC subtypes.

Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET)-based imaging agents for prostate carcinoma and neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein summarized under the umbrella term molecular imaging reporting and data systems (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging are described (PSMA- and SSTR-RADS). Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e., if the reader is familiar with one system, the other system can readily be applied, as well. In the present review, we will discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly introduce PSMA- and SSTR-RADS, and define a potential future role of the umbrella framework MI-RADS compared to other classification systems.

Synthetic marijuana is a dangerous substance due to its potency, ever-changing composition, and unpredictable side effects. Recently, brodifacoum-contaminated synthetic marijuana has led to multiple deaths and morbidity throughout the USA from severe coagulopathy associated with use of this strain of the drug (brodifacoum is a rodenticide and potent Vitamin K antagonist/anticoagulant). We describe the clinical and radiologic findings in two patients who were diagnosed with, and treated for, ingestion of this new strain of synthetic marijuana. The radiologic manifestations were most notable for hemorrhagic pyelitis/ureteritis. Both patients required hospitalization with Vitamin K supplementation. The radiologic and clinical pictures in these patients are important for radiologists to recognize in order to help guide appropriate patient management.

Adrenalectomy is the standard of care for management of many adrenal tumor types and, in the United States alone, approximately 6000 adrenal surgeries are performed annually. Two general approaches to adrenalectomy have been described; (1) the open approach, in which a diseased adrenal is removed through a large (10-20 cm) abdominal wall incision, and (2) the minimally invasive approach, in which laparoscopy is used to excise the gland through incisions generally no longer than 1-2 cm. Given these disparate technique options, clear preoperative characterization of those specific disease features that inform selection of adrenalectomy approach is critically important to the surgeon. Because most of these features are directly assessed via preoperative abdominal imaging, in particular computed tomography (CT) scanning, a clear mutual understanding among surgeons and radiologists of those adrenal tumor features impacting operative approach selection is vital for planning adrenal surgery. In this context, we review the preoperative CT imaging features that specifically inform adrenalectomy approach selection, provide illustrative examples from our institution's imaging and surgical archives, and provide a stepwise guide to both the open and laparoscopic adrenalectomy approaches.

3D visualization methods for volumetric CT data have played an important role in diagnostic imaging of the small bowel, a structure which intrinsically crosses numerous slices in any 2D imaging plane. Recently, a new approach to 3D CT image creation has become available-cinematic rendering (CR). CR differs from other 3D methods in making use of a global lighting model that produces high surface detail and realistic shadowing effects that lead to 3D visualizations with photorealistic quality. Although the utility of these images for improving diagnostic accuracy has not yet been established, our group's early experience in regions of complex anatomy and pathology has been encouraging. In this pictorial review, we review the established role of 3D CT in many of the most common small bowel pathologies, provide examples of those pathologies visualized with CR, and suggest future directions for researchers to pursue.

Kawasaki's disease (KD) is a vasculitis that predominantly affects children and can lead to the development of coronary artery aneurysms. These aneurysms can subsequently thrombose and occlude, which may lead to chest pain and other signs and symptoms of acute coronary syndrome in young patients. Coronary CT angiography, including 3D visualization techniques, is a common modality used in the follow-up of KD patients. In this series of three patients, we present the typical coronary artery imaging findings that can appear in these patients, with an emphasis on the use of the novel 3D technique of cinematic rendering (CR). CR utilizes a different lighting model than other 3D methods and is able to produce highly-detailed, photorealistic images. The potential advantages of CR images in understanding the complex mediastinal vascular anatomy and the relationships of coronary artery aneurysms to other anatomic structures are emphasized.

Acute aortic injuries are not common in the setting of severe blunt trauma, but lead to significant morbidity and mortality. High-quality MDCT with 2D MPRs and 3D rendering are essential to identify aortic trauma and distinguish anatomic variants and other forms of aortic pathology from an acute injury. Misinterpretation of mimics of acute aortic injury can lead to unnecessary arteriography and thoracic surgery. Since most traumatic injuries occur in the distal arch, radiologists must be cognizant of the range of appearances of variants related to the ductus diverticulum. Cinematic rendering (CR) is a new 3D post-processing tool that provides even greater anatomic detail than traditional volume rendering. In this case series, CR is used to impart to radiologists a better understanding of various anatomic configurations that can be seen with a ductus diverticulum.

Technetium-99m (99mTc)-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has previously been shown to allow for the accurate differentiation of benign renal oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs) apart from other malignant renal tumor histologies, with oncocytomas/HOCTs showing high uptake and renal cell carcinoma (RCC) showing low uptake based on uptake ratios from non-quantitative single-photon emission computed tomography (SPECT) reconstructions. However, in this study, several tumors fell close to the uptake ratio cutoff, likely due to limitations in conventional SPECT/CT reconstruction methods. We hypothesized that application of quantitative SPECT/CT (QSPECT) reconstruction methods developed by our group would provide more robust separation of hot and cold lesions, serving as an imaging framework on which quantitative biomarkers can be validated for evaluation of renal masses with 99mTc-sestamibi. Single-photon emission computed tomography data were reconstructed using the clinical Flash 3D reconstruction and QSPECT methods. Two blinded readers then characterized each tumor as hot or cold. Semi-quantitative uptake ratios were calculated by dividing lesion activity by background renal activity for both Flash 3D and QSPECT reconstructions. The difference between median (mean) hot and cold tumor uptake ratios measured 0.655 (0.73) with the QSPECT method and 0.624 (0.67) with the conventional method, resulting in increased separation between hot and cold tumors. Sub-analysis of 7 lesions near the separation point showed a higher absolute difference (0.16) between QPSECT and Flash 3D mean uptake ratios compared to the remaining lesions. Our finding of improved separation between uptake ratios of hot and cold lesions using QSPECT reconstruction lays the foundation for additional quantitative SPECT techniques such as SPECT-UV in the setting of renal 99mTc-sestamibi and other SPECT/CT exams. With robust quantitative image reconstruction and biomarker analysis, there may be an expanded role for SPECT/CT imaging in renal masses and other pathologic conditions.

To explore the clinical utility of PSMA-targeted 18F-DCFPyL PET/CT in patients with metastatic urothelial carcinoma. Three patients with metastatic urothelial carcinoma were imaged with 18F-DCFPyL PET/CT. All lesions with perceptible radiotracer uptake above background were considered positive. Maximum standardized uptake values were recorded for each detected lesion and findings on 18F-DCFPyL PET/CT were compared to those on conventional imaging studies. To further explore PSMA as a molecular target of urothelial carcinoma, RNA-sequencing data from The Cancer Genome Atlas were used to compare the relative expression of PSMA among cases of bladder cancer, prostate cancer, and clear cell renal cell carcinoma. Additionally, immunohistochemical staining for PSMA was performed on a biopsy specimen from one of the imaged patients. 18F-DCFPyL PET/CT allowed for the detection of sites of urothelial carcinoma, albeit with low levels of radiotracer uptake. Analysis of RNA-sequencing data revealed that bladder cancer had significantly lower levels of PSMA expression than both prostate cancer and clear cell renal cell carcinoma. Consistent with this observation, immunohistochemical staining of tissue from one of the imaged patients demonstrated a low level of neovascularization and nearly absent PSMA expression. The relatively scant expression of PSMA by urothelial carcinoma likely limits the utility of PSMA-targeted PET imaging of this malignancy. Future research efforts should focus on the development of other molecularly targeted imaging agents for urothelial carcinoma.

Current standard of care conventional imaging modalities (CIM) such as X-ray computed tomography (CT) and bone scan can be limited for detection of metastatic prostate cancer and therefore improved imaging methods are an unmet clinical need. We evaluated the utility of a novel second-generation low molecular weight radiofluorinated prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) radiotracer, [(18)F]DCFPyL, in patients with metastatic prostate cancer.Nine patients with suspected prostate cancer recurrence, eight with CIM evidence of metastatic prostate cancer and one with biochemical recurrence, were imaged with [(18)F]DCFPyL PET/CT. Eight of the patients had contemporaneous CIM for comparison. A lesion-by-lesion comparison of the detection of suspected sites of metastatic prostate cancer was carried out between PET and CIM. Statistical analysis for estimated proportions of inter-modality agreement for detection of metastatic disease was calculated accounting for intra-patient correlation using general estimating equation (GEE) intercept-only regression models.One hundred thirty-nine sites of PET positive [(18)F]DCFPyL uptake (138 definite, 1 equivocal) for metastatic disease were detected in the eight patients with available comparison CIM. By contrast, only 45 lesions were identified on CIM (30 definite, 15 equivocal). When lesions were negative or equivocal on CIM, it was estimated that a large portion of these lesions or 0.72 (95 % confidence interval (CI) 0.55-0.84) would be positive on [(18)F]DCFPyL PET. Conversely, of those lesions negative or equivocal on [(18)F]DCFPyL PET, it was estimated that only a very small proportion or 0.03 (95 % CI 0.01-0.07) would be positive on CIM. Delayed 2-h-post-injection time point PET yielded higher tumor radiotracer uptake and higher tumor-to-background ratios than an earlier 1-h-post-injection time point.A novel PSMA-targeted PET radiotracer, [(18)F]DCFPyL, was able to a large number of suspected sites of prostate cancer, many of which were occult or equivocal by CIM. This study provides strong preliminary evidence for the use of this second-generation PSMA-targeted PET radiotracer for detection of metastatic prostate cancer and lends further support for the importance of PSMA-targeted PET imaging in prostate cancer.

Determining the metastatic viability of suspicious retroperitoneal nodes in testicular cancer with conventional imaging is challenging. The aim of this report is to review recent evidence in the utilization of novel imaging modalities to assess viable testicular cancer nodal metastases. Testicular germ cell tumors (TCGTs) follow a predictable lymphatic metastatic spread to the retroperitoneum. Accordingly, retroperitoneal imaging is critical in staging, assessing treatment response, and evaluating for recurrence. Conventional computed tomography (CT) imaging is effective in diagnosing pathologically enlarged lymph nodes but lacks the molecular information to determine if suspicious nodes harbor viable tumor. Positron emission tomography (PET) with the metabolic radiotracer 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG or FDG) has been shown to be useful in determining the presence of or absence of viable tumor after chemotherapy for seminoma, but its role with non-seminomatous germ cell tumors (NSGCTs) and other clinical scenarios is limited. Patients with residual masses after chemotherapy for NSGCT present a difficult challenge because surgical resection carries a high degree of morbidity despite many patients only harboring fibrosis on final pathology. Current imaging modalities are unable to effectively differentiate fibrosis from viable tumor on preoperative imaging. Novel molecular imaging techniques present promising opportunities to improve diagnosis in these patients. Novel imaging platforms have potential to improve the ability to determine viable nodal metastases regardless of size and structure but confirmatory studies are currently lacking.

Molecular imaging with positron emission tomography (PET) provides a powerful means of identifying and characterizing cancerous processes, as well as providing a quantitative framework within which response to therapy can be ascertained. Unfortunately, the most commonly used PET radiotracer, ¹⁸F-fluorodeoxyglucose (FDG), has not demonstrated a definitive role in determining response to therapy in metastatic renal cell carcinoma (RCC). As a result, new radiotracers able to reliably image RCC could be of tremendous value for this purpose.Five patients with known metastatic RCC were imaged with the low-molecular weight radiotracer ¹⁸F-DCFPyL, an inhibitor of the prostate-specific membrane antigen at 60 min post injection. ¹⁸F-DCFPyL PET/CT and conventional images (either contrast-enhanced computed tomography or magnetic resonance imaging) were centrally reviewed for suspected sites of disease.In all five patients imaged, sites of putative metastatic disease were readily identifiable by abnormal ¹⁸F-DCFPyL uptake, with overall more lesions detected than on conventional imaging. These PET-detected sites included lymph nodes, pancreatic parenchymal lesions, lung parenchymal lesions, a brain parenchymal lesion, and other soft tissue sites. ¹⁸F-DCFPyL uptake ranged from subtle to intense with maximum standardized uptake values (SUVmax) for the identified lesions of 1.6-19.3. Based upon this small patient series, limited pathology and imaging follow-up of these patients suggests a higher sensitivity for ¹⁸F-DCFPyL compared to conventional imaging in the detection of metastatic RCC (94.7 versus 78.9%).PSMA expression in the tumor neovasculature of RCC has been previously established and is believed to provide the basis for the imaging findings presented here. PSMA-based PET/CT with radiotracers such as ¹⁸F-DCFPyL may allow more accurate staging of patients with RCC and conceivably the ability to predict and follow therapy in patients treated with agents targeting the neovasculature.

Prostate-specific membrane antigen (PSMA) is a recognized target for imaging prostate cancer. Here we present initial safety, biodistribution, and radiation dosimetry results with [(18)F]DCFPyL, a second-generation fluorine-18-labeled small-molecule PSMA inhibitor, in patients with prostate cancer.Biodistribution was evaluated using sequential positron-emission tomography (PET) scans in nine patients with prostate cancer. Time-activity curves from the most avid tumor foci were determined. The radiation dose to selected organs was estimated using OLINDA/EXM.No major radiotracer-specific adverse events were observed. Physiologic accumulation was observed in known sites of PSMA expression. Accumulation in putative sites of prostate cancer was observed (SUVmax up to100, and tumor-to-blood ratios up to50). The effective radiation dose from [(18)F]DCFPyL was 0.0139 mGy/MBq or 5 mGy (0.5 rem) from an injected dose of 370 MBq (10 mCi).[(18)F]DCFPyL is safe with biodistribution as expected, and its accumulation is high in presumed primary and metastatic foci. The radiation dose from [(18)F]DCFPyL is similar to that from other PET radiotracers.

Prostate-specific membrane antigen (PSMA) is expressed by prostate cancer cells as well as endothelial cells within the neovasculature of a number of malignancies including renal cell carcinoma (RCC). PET radiotracers that target PSMA have shown great promise for imaging RCC. Agents that target PSMA also have the potential to be used as therapeutics in patients with this malignancy.