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Background Prostate-specific membrane antigen (PSMA) is a rational target for noninvasive detection of recurrent prostate cancer (PCa) and for therapy of metastatic castration-resistant prostate cancer (mCRPC) with PSMA-targeted agents. Here we conducted serial measurements of PSMA expression on circulating tumor cells (CTCs) to evaluate patterns of longitudinal PSMA dynamics over the course of multiple sequential therapies. Methods A retrospective investigation of men with mCRPC undergoing evaluation at medical oncology clinics at our institution assessed the dynamics of PSMA expression in the context of different systemic treatments administered sequentially. Eligibility included patients who began systemic therapies with androgen receptor (AR)-directed agents or taxane agents for whom peripheral blood samples were tested for CTC mRNA of AR splice variant-7 (AR-V7), prostate-specific antigen (PSA), and PSMA (with >2 CTC + results) in a CLIA-accredited laboratory. Results From August 2015 to November 2017, we identified 96 eligible men. Fifteen had greater than or equal to 2 sequential therapies and evaluable CTC samples, greater than or equal to 1 expressing PSMA (PSMA+). Among the 15 patients included in this analysis, a total of 54 PSMA status evaluations were performed in the context of 48 therapies during a median follow-up of 18 months. At baseline, PSMA signal was detected ("positive") in 11 of 15 (73.3%) patients, while for 4 of 15 (26.7%) patients PSMA signal was undetectable ("negative"). In all but two patients, the baseline collection corresponded with a change in treatment. On the second assessment, PSMA increases were detected in all 4/4 (100%) PSMA-negative patients and 8 of 11 (72.7%) PSMA-positive patients. PSMA significantly decreased in a patient treated with 177 Lu-PSMA-617. Serum PSA declines were seen in 7 of 8 (88%) of the treatment periods where PSMA decreased. Conclusions PSMA expression in CTCs is a dynamic marker. PSMA transcript declines appear to be associated with concurrent decreases in serum PSA. Sequential CTC sampling could provide a noninvasive response assessment to systemic treatment for mCRPC.

Skin and subcutaneous (SQ) findings are important clinical clues in assessing the mechanism and severity of traumatic injury. These findings can help the radiologist pinpoint the site of injury and perform a focused assessment of the underlying deeper tissues. However, these clues are difficult to perceive on 2D CT images and can be overlooked. Cinematic rendering (CR) is a novel 3D imaging technique that generates photorealistic views based on a new lighting model. CR can be optimized to provide renderings of the skin, SQ tissues, and underlying musculature. Depth perception, soft tissue differentiation, as well as the visualization of lacerations and gunshot wounds can also be enhanced by CR. Potentially significant information in assessing the extent of acute trauma and associated complications can be gleaned through the use of CR.

Cinematic rendering (CR) is a recently described three-dimensional (3D) rendering technique that generates photorealistic images based on a new lighting model. This review illustrates the potential application of CR in the evaluation of focal liver masses. CR shows promise in improving the visualization of enhancement pattern and internal architecture, local tumor extension, and global disease burden, which may be helpful in focal liver mass characterization and pretreatment planning.

BACKGROUND: Modern medicine emphasizes high-value precision care. Within the context of precision health, leveraging clinical, genetic, and radiomic data in combination with applications of machine learning holds great promise in uncovering patterns within patients’ groups that may ultimately inform personalized therapeutic intervention. On the other hand, studies using positron emission tomography (PET) with radiotracers designed to bind molecular targets specifically are too small in size for this data-mining approach, and shared, substantive databases of PET data are in early stages of development. Nevertheless, the success of precision psychiatry in the years ahead is arguably limited without continued efforts using PET neuroimaging in vivo to characterize the molecular changes relevant to the pathophysiology of psychiatric conditions like psychosis. METHODS: We present several new PET-based imaging agents that we designed to specifically target key proteins relevant to studying altered neuroimmunity across and within diagnostic groups of patients. First, among our radiochemistry efforts, we recently developed [18F]FNDP, which binds soluble epoxide hydrolase (sEH), an enzyme that controls the bioavailability of epoxyeicosatrienoic acids that have vasoactive and anti-inflammatory roles. sEH has been found to be elevated in post-mortem brain tissue from individuals with psychosis. Second, we developed [18F]ASEM that targets the alpha7 nicotinic acetylcholine receptor (α7-nAChR), which has a role in anti-inflammatory cholinergic signaling. Building on postmortem evidence of low hippocampal expression of the α7-nAChR in patients with non-affective psychosis (NP), we used [18F]ASEM PET to test whether individuals with NP have lower [18F]ASEM binding compared to healthy individuals or individuals with affective psychotic disorder (AP). Finally, we recently developed [11C]CMPPF for imaging the microglia-specific target, colony stimulating factor 1 receptor (CSF-1R), due to evidence that activated microglia may be mechanistically linked to psychosis in some individuals. RESULTS: After bolus injection of [18F]FNDP, high levels of brain radioactivity were observed in healthy participants, with peak gray matter activity within 10 minutes post injection and steady decline over the remaining scan. [18F]FNDP total distribution volume (VT) was well-estimated in several brain regions from 90-minute data using the 2-tissue compartment model with metabolite-corrected arterial input function, supporting early efforts to use [18F]FNDP PET in clinical research. Using [18F]ASEM PET, VT was lower in individuals with NP (14.1 ± 0.9) compared to healthy controls (19.6 ± 2.5, P < 0.001) or compared to those with AP (17.6 ± 2.2, P = 0.04). Among patients, higher [18F]ASEM VT was associated with better processing speed and verbal memory after adjusting for age. Finally, [11C]CMPPF with PET in living baboon brain shows promising, high uptake and specific binding, as well as higher VT after systemic administration of lipopolysaccharide to activate microglia. Movement of this radiotracer into human neuroimaging studies is underway toward the ultimate goal of testing whether [11C]CMPPF PET supports the hypothesized subgroup of individuals with psychosis who have aberrantly high microglial response. CONCLUSIONS: Use of PET-based imaging even in smaller-scale studies may facilitate clinically meaningful subtyping of individuals with aberrant neuroimmune response among those with psychosis. Future work should pursue evaluation of approaches such as a generative adversarial network to augment what can be discovered from relatively small PET samples, and assessment of clinical decision-making value from use of a growing number of radiotracers for PET-based molecular phenotyping of subpopulations of patients.

INTRODUCTION AND OBJECTIVES:Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is overexpressed by prostate cancer (PCa) cells and can be targeted using the novel PET radiotr...

OBJECTIVE: 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 (18)F-DCFPyL PET/CT in patients with presumed oligometastatic clear cell RCC. METHODS: This is a subset analysis of a prospective study in which patients with RCC were imaged with (18)F-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. (18)F-DCFPyL PET/CT scans were reviewed for sites of disease and compared to conventional imaging. RESULTS: The final cohort included 14 patients with oligometastatic clear cell RCC. Conventional imaging revealed 21 metastatic lesions and 3 primary tumors. (18)F-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 (18)F-DCFPyL PET/CT than conventional imaging. Notably, 3 (21.4%) patients were no longer considered oligometastatic. The detection rates of conventional imaging and (18)F-DCFPyL PET/CT for identifying sites of disease were 66.7% and 88.9%, respectively. CONCLUSIONS: 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.

Although single-photon-emitting radiotracers have long been the standard for renal functional molecular imaging, recent years have seen the development of positron emission tomography (PET) agents for this application. We provide an overview of renal radionuclide PET radiotracers, in particular focusing on novel 18F-labelled and 68Ga-labelled agents. Several reported PET imaging probes allow assessment of glomerular filtration rate, such as [68Ga]ethylenediaminetetraacetic acid ([68Ga]EDTA), [68Ga]IRDye800-tilmanocept and 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS)). The diagnostic performance of [68Ga]EDTA has already been demonstrated in a clinical trial. [68Ga]IRDye800-tilmanocept shows receptor-mediated binding to glomerular mesangial cells, which in turn may allow the monitoring of progression of diabetic nephropathy. [18F]FDS shows excellent kidney extraction and excretion in rats and, as has been shown in the first study in humans. Further, due to its simple one-step radiosynthesis via the most frequently used PET radiotracer 2-deoxy-2-[18F]fluoro-d-glucose, [18F]FDS could be available at nearly every PET centre. A new PET radiotracer has also been introduced for the effective assessment of plasma flow in the kidneys: Re(CO)3-N-([18F]fluoroethyl)iminodiacetic acid (Re(CO)3([18F]FEDA)). This compound demonstrates similar pharmacokinetic properties to its 99mTc-labelled analogue [99mTc](CO)3(FEDA). Thus, if there is a shortage of molybdenum-99, Re(CO)3([18F]FEDA would allow direct comparison with previous studies with 99mTc. The PET radiotracers for renal imaging reviewed here allow thorough evaluation of kidney function, with the tremendous advantage of precise anatomical coregistration with simultaneously acquired CT images and rapid three-dimensional imaging capability.

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

Cinematic rendering (CR) is a new 3D visualization methodology for volumetric diagnostic imaging including computed tomography (CT) datasets composed of isotropic voxels. CR produces photorealistic images with enhanced detail relative to other 3D visualization methods and realistic shadowing. In this review, we provide a number of examples of splenic pathology visualized with CR including conditions affecting the splenic vasculature, neoplasms, and accessory spleens. These examples are compared to 2D CT and traditional 3D CT techniques and the potential advantages of CR are highlighted. CR displays textural changes in the splenic parenchyma to particular advantage, and a portion of this review will be devoted to examples of how textural features can help distinguish intrapancreatic accessory spleens from neuroendocrine tumors.

We present the case of a 71-year-old man with Gleason 3+3=6 pT2N0MxR0 adenocarcinoma of the prostate who presented with rising PSA level sixteen years following radical prostatectomy. PSMA-targeted (18)F-DCFPyL PET/CT was performed, which demonstrated recurrent disease in the prostatectomy bed as well as splenomegaly and mild-diffuse bone marrow activation, consistent with the patient’s history of hereditary spherocytosis. We briefly review the clinical characteristics of hereditary spherocytosis, its appearance on molecular imaging studies, the normal biodistribution of (18)F-DCFPyL, and the PSMA-RADS scoring system for characterizing findings on PSMA-targeted PET imaging.

Beyond commonly used myocardial perfusion imaging (MPI) radiotracers compatible with single-photon emission computed tomography (SPECT) imaging, positron emission tomography (PET) agents offer several key advantages. Nonetheless, the short half-life of clinically used PET MPI radiotracers limits a

Recent years have witnessed an expanded use of single-photon emission CT and PET for a wide range of clinical applications, including imaging of brain abnormalities. As a result, molecular brain imaging is now being more extensively utilized in criminal cases, in particular in the sentencing phase of a trial. This perspective aims to provide a brief overview for the practicing radiologist of this expanded use of single-photon emission CT and PET in criminal cases and will discuss the role of radiology in this field.

In nuclear cardiology, numerous single-photon emission computed tomography radiotracers have been advocated to reflect various cardiac metabolic and functional conditions, but positron emission tomography (PET) may offer a more thorough evaluation, mainly due to superior characteristics associated with the latter imaging modality. This shift in recent years has been fueled by the introduction of

In nuclear cardiology, numerous single-photon emission computed tomography radiotracers have been advocated to reflect various cardiac metabolic and functional conditions, but positron emission tomography (PET) may offer a more thorough evaluation, mainly due to superior characteristics associated with the latter imaging modality. This shift in recent years has been fueled by the introduction of 18F-labeled PET radiotracers. Due to physical and chemical key properties, these imaging agents allow for more flexibility of imaging protocols and a better employment in the clinic. Potentially rendering perfusion, viability, innervation and inflammation, 18F-labeled PET radiotracers may truly pave the way for a global assessment of the current metabolic and functional status of the heart, e.g. after acute myocardial infarction or for progressed heart failure. The present review aims to provide a precise overview of those recently introduced 18F-labeled cardiac imaging agents and how those state-of-the-art, top-tier radiotracers may redefine precision medicine in cardiology.

BACKGROUND: Monotherapy with immune checkpoint inhibitors has generally been unsuccessful in men with advanced prostate cancer. Preclinical data support the notion that cryotherapy may improve immune-mediated and anti-tumor responses. The objective of this study was to assess the safety and feasibility of whole-prostate gland cryotherapy combined with pembrolizumab and androgen deprivation in men with oligometastatic hormone-sensitive prostate cancer. METHODS: This single-institution, pilot trial recruited 12 patients with newly diagnosed oligometastatic prostate cancer between 2015 and 2016. Patients underwent whole-prostate cryoablation combined with short-term androgen deprivation (eight months) and pembrolizumab (6 doses). The primary clinical endpoints were the number of patients with a PSA level of

More than 20 years ago, Dr. Zhu from China said, “As the world-renowned achievements of radioimmunoassay for trace substance detection are attributed to the multidisciplinary effect of nuclear medicine and immunology, likewise, success of radioimmunoimaging (RII) and radioimmunotherapy (RIT) are dependent on the interaction of these two disciplines, which opens up a new way for the diagnosis and treatment of cancer.” RII and RIT, together termed radioimmunotheranostics, are characterized by radioisotope-labeled antibody or fragments which can recognize some specific antigen; the ultimate goal of which is to diagnose or treat cancer or other diseases. Radioimmunotheranostics has a 70-year history of development, and numerous scholars who came from diverse fields including medicine, immunology, bioengineering, etc. dedicated in this field made unremittent efforts for human health. With the rapid development of medical and bioengineering technology, novel theranostic probes, which can recognize a specific antigen on the cancer cell or are associated with the tumor microenvironment, are not limited to antibodies but include some small-molecule ligands. In this chapter, we would also give some introduction of radionuclide-labeled non-antibody imaging and therapy, while the major focus will be on traditional RII and RIT.

High-grade gliomas (World Health Organization grade III–IV) are highly lethal primary brain tumors. Imaging modalities, including MRI and FDG PET, provide a limited ability to differentiate treatment effects (such as radiation necrosis) from recurrent or residual tumor. As the first step in validating the applicability of prostate-specific membrane antigen (PSMA)– targeted imaging in high-grade gliomas, we evaluated the ability of the PSMA-targeted small molecule [18F]DCFPyL (2-(3-(1carboxy-5-(6-[18F] fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid) to image high-grade gliomas in a series of 3 prospectively recruited patients. We found [18F]DCFPyL binds PSMA in the neovasculature of glioblastoma multiforme and tumor cells of anaplastic astrocytoma.

Chimeric antigen receptor (CAR) T cell therapy for hematologic malignancies is fraught with several unknowns, including number of functional T cells that engage target tumor, durability and subsequent expansion and contraction of that engagement, and whether toxicity can be managed. Non-invasive, serial imaging of CAR T cell therapy using a reporter transgene can address those issues quantitatively. We have transduced anti-CD19 CAR T cells with the prostate-specific membrane antigen (PSMA) because it is a human protein with restricted normal tissue expression and has an expanding array of positron emission tomography (PET) and therapeutic radioligands. We demonstrate that CD19-tPSMA(N9del) CAR T cells can be tracked with [18F]DCFPyL PET in a Nalm6 model of acute lymphoblastic leukemia. Divergence between the number of CD19-tPSMA(N9del) CAR T cells in peripheral blood and bone marrow and those in tumor was evident. These findings underscore the need for non-invasive repeatable monitoring of CAR T cell disposition clinically.

Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB), and key TB antimicrobials, including rifampin, have restricted brain penetration. A lack of reliable data on intralesional drug biodistribution in infected tissues has limited pharmacokinetic (PK) modeling efforts to optimize TBM treatments. Current methods to measure intralesional drug distribution rely on tissue resection, which is difficult in humans and generally limited to a single time point even in animals. In this study, we developed a multidrug treatment model in rabbits with experi­ mentally induced TBM and performed serial noninvasive dynamic (11)C-rifampin positron emission tomography (PET) over 6 weeks. Area under the curve brain/plasma ratios were calculated using PET and correlated with postmortem mass spectrometry. We demonstrate that rifampin penetration into infected brain lesions is limited, spa­ tially heterogeneous, and decreases rapidly as early as 2 weeks into treatment. Moreover, rifampin concentrations in the cerebrospinal fluid did not correlate well with those in the brain lesions. First-in-human (11)C-rifampin PET performed in a patient with TBM confirmed these findings. PK modeling predicted that rifampin doses (≥30 mg/kg) were required to achieve adequate intralesional concentrations in young children with TBM. These data demonstrate the proof of concept of PET as a clinically translatable tool to noninvasively measure intralesional antimicrobial distribution in infected tissues.

Renal tumors are increasing in incidence, at least partly on the basis of incidental detection during the routine use of abdominal imaging for non-genitourinary indications. Conventional imaging with anatomic modalities such as computed tomography, magnetic resonance imaging, and ultrasound constitute not only the most common method by which renal tumors are identified but also form the backbone for characterizing certain aspects of renal masses. Characterization with conventional imaging generally focuses on determining the solid or cystic nature of a mass, defining the size of the mass, local tumor staging, and evaluation for the presence of metastases. For many renal masses, conventional imaging fails to provide accurate assessment of the tumor’s histologic type, and for this reason molecular imaging techniques are being actively investigated as means to noninvasively risk-stratify patients and appropriately triage those patients who harbor benign or indolent renal masses to active surveillance. In this chapter, we will summarize modern anatomic and molecular methods of imaging renal tumors.

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.

As has been previously reported, the somatostatin receptor (SSTR) imaging agent [Of the 44 included patients, 36/44 (82 %) patients demonstrated suspicious radiotracer uptake on [The median SUVThere is no significant impact on normal organ biodistribution with increasing tumor burden on [

32 Background: Conventional imaging and bone scintigraphy are suboptimal modalities for identifying PCa. PSMA-based imaging is highly promising for PCa detection. 18F-DCFPyL is a novel PSMA-targeted radiopharmaceutical for positron emission tomography (PET) that may be useful in staging of PCa. The diagnostic performance, detection rate, and potential impact of 18F-DCFPyL on staging of pts with high- risk PCa have been previously reported. Here we report on the impact of 18F-DCFPyL on staging of pts with PCa recurrence or metastases on conventional imaging. Methods: 18F-DCFPyL-PET/CT was evaluated in 117 men with radiologic evidence of local recurrence or metastatic disease on baseline anatomical imaging (CT, MRI) or whole-body bone scintigraphy and in whom at least one lesion was deemed amenable to biopsy. A single dose of 9 mCi (333 MBq) of 18F-DCFPyL was administered via intravenous injection, followed by PET/CT acquisition 1 to 2 hours thereafter. Based on TNM staging: prostatic (T), pelvic LN (N), extra-pelvic LN (M1a), bone (M1b) and other visceral organs/soft tissue (M1c), 18F-DCFPyL-PET/CT detection rates including lesion counts were systematically analyzed. Three central, blinded, and independent readers evaluated the 18F-DCFPyL scans. Results: In this study, 82 (70%) patients had baseline radiographic M1 stage disease (14 patients with M1a, 50 patients with M1b, 18 patients with M1c) and 33 (28%) patients were M0 stage at baseline by central conventional imaging review; two patients were unevaluable. 18F-DCFPyL-PET/CT up-staged 58% (19/33) of pts from M0 to M1, of whom 91% (10/11) who underwent an extra-pelvic biopsy were confirmed to have M1 disease by pathology, including 9 patients with M1b and 1 patient with M1a. Of the patients who were staged M1 at baseline, 18F-DCFPyL-PET/CT upstaged 16% (10/64; M1a to M1b or M1c: n = 4; M1b to M1c: n = 6) of pts to a higher M1 sub-stage and down-staged 22% (18/82) to M0. Conclusions: 18F-DCFPyL-PET/CT identified M1 disease in the majority of patients examined who otherwise had locoregional disease. These data suggest that 18F-DCFPyL-PET/CT may be a useful tool in properly staging men with both metastatic and nonmetastatic relapsed disease, which could lead to superior treatment paradigms than currently exist using conventional imaging. Clinical trial information: NCT02981368.

// Il Minn 1 , Soo Min Koo 1 , Hye Soo Lee 1 , Mary Brummet 1 , Steven P. Rowe 1 , Michael A. Gorin 2 , Polina Sysa-Shah 1 , William D. Lewis 1 , Hye-Hyun Ahn 1 , Yuchuan Wang 1 , Sangeeta Ray Banerjee 1 , Ronnie C. Mease 1 , Sridhar Nimmagadda 1 , Mohamad E. Allaf 2 , Martin G. Pomper 1 , Xing Yang 1 1 Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA 2 The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Correspondence to: Martin G. Pomper, email: mpomper@jhmi.edu Xing Yang, email: xyang45@jhmi.edu Keywords: carbonic anhydrase IX, positron emission tomography, molecular imaging, renal cell carcinoma, copper-64 Received: February 25, 2016 Accepted: June 09, 2016 Published: July 14, 2016 ABSTRACT Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95% of cases of clear cell renal cell carcinoma (ccRCC), the most common renal cancer. We synthesized and performed in vitro and in vivo evaluation of a dual-motif ligand, [ 64 Cu]XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [ 64 Cu]XYIMSR-06 was generated in yields of 51.0 ± 4.5% (n=5) and specific activities of 4.1 – 8.9 GBq/μmol (110-240 Ci/mmol). Tumor was visualized on PET images by 1 h post-injection with high tumor-to-background levels (>100 tumor-to-blood and -muscle) achieved within 24 h. Biodistribution studies demonstrated a maximum tumor uptake of 19.3% injected dose per gram of radioactivity at 4 h. Tumor-to-blood, -muscle and -kidney ratios were 129.6 ± 18.8, 84.3 ± 21.0 and 2.1 ± 0.3, respectively, at 8 h post-injection. At 24 h a tumor-to-kidney ratio of 7.1 ± 2.5 was achieved. These results indicate pharmacokinetics superior to those of previously reported imaging agents binding to CAIX. [ 64 Cu]XYIMSR-06 is a new low-molecular-weight PET ligand targeting CAIX, which can image localized and metastatic ccRCC.

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.

Nuclear imaging offers a potential noninvasive means of determining the histology of renal tumors. The aim of this study was to evaluate the accuracy of technetium-99m ( 99m Tc)–sestamibi single-photon emission computed tomography/x-ray computed tomography (SPECT/CT) for the differentiation of oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs) from other renal tumor histologies. In total, 50 patients with a solid clinical T1 renal mass were imaged with 99m Tc-sestamibi SPECT/CT prior to surgical resection. Preoperative SPECT/CT scans were reviewed by two blinded readers, and their results were compared with centrally reviewed surgical pathology data. Following surgery, 6 (12%) tumors were classified as renal oncocytomas and 2 (4%) as HOCTs. With the exception of 1 (2%) angiomyolipoma, all other tumors were renal cell carcinomas (82%). 99m Tc-sestamibi SPECT/CT correctly identified 5 of 6 (83.3%) oncocytomas and 2 of 2 (100%) HOCTs, resulting in an overall sensitivity of 87.5% (95% confidence interval [CI], 47.4−99.7%). Only two tumors were falsely positive on SPECT/CT, resulting in a specificity of 95.2% (95% CI, 83.8−99.4%). In summary, 99m Tc-sestamibi SPECT/CT is a promising imaging test for the noninvasive diagnosis of renal oncocytomas and HOCTs. Patient summary We found that the imaging test 99m Tc-sestamibi SPECT/CT can be used to accurately diagnose two types of benign kidney tumors. This test may be eventually used to help better evaluate patients diagnosed with a renal tumor.

Imaging of bone metastases in prostate cancer has traditionally involved planar Tc-methylene diphosphonate (Tc-MDP) bone scan with or without the use of supplemental tomographic imaging. More recently, NaF positron emission tomography/x-ray computed tomography (PET/CT) has been found to have improved sensitivity and specificity for sites of osseous metastatic involvement. Prostate-specific membrane antigen (PSMA) is a cell surface enzyme that is highly expressed in prostate cancer and has been explored as a target for prostate cancer imaging. In this case report, we found that PSMA-based PET/ CT with the small molecule F-DCFPyL detected a large number of bony lesions that were occult on Tc-MDP bone scan and NaF PET/CT. PSMA-targeted PET/CT may offer improved sensitivity by binding directly to tumor cells, as opposed to localizing to sites of bony reaction. This preliminary finding should be further explored in larger studies.

Cystic lymphangioma is an uncommon lesion in the adrenal gland. Because of the lesion's rarity, few descriptions of it can be found in the radiology literature. We therefore describe a series of these lesions with a focus on CT characteristics with correlation to gross and microscopic pathology features.Retrospective review identified seven patients with definitive pathologic findings of cystic lymphangioma of the adrenal gland and available diagnostic CT examinations. CT examinations were reviewed for key imaging features and correlated to gross and microscopic pathology. Lesions were generally described in corresponding reports as likely representing adenomas or hematomas based on CT findings.All cystic lymphangiomas included in this series were well-circumscribed lesions with low-attenuation internal contents and thin walls, without evidence of solid components or nodularity. No measurable contrast enhancement was seen in these lesions. Six of the seven lesions contained calcifications with one of two patterns: either thick, curvilinear, and dystrophic-appearing or thin and scattered. On gross and microscopic pathology, the lesions were composed of dilated cystic spaces containing serous fluid and lined by bland endothelial cells.Though rare, an adrenal cystic lymphangioma should be suspected on CT when a unilocular or multilocular, low-attenuation, nonenhancing lesion is present in the region of the adrenal gland, particularly if the lesion contains either of the above-noted calcification patterns. Recognition of these findings may allow more conservative treatment of selected patients harboring these lesions.

Objective A series of renal hybrid oncocytic/chromophobe tumors (HOCTs) was retrospectively assessed for morphologic features and enhancement characteristics by computed tomography (CT). Materials (subjects) and methods Nine patients with pathologically proven HOCTs were identified. These patients harbored a total of 12 lesions. All patients had available preoperative contrast-enhanced CT examinations, although a proportion of the studies had been carried out at outside institutions. The morphologic characteristics and enhancement patterns of each tumor were evaluated systematically. Results Seventy-eight percent of the patients were men, with a mean age of 62 years. None of the patients had evidence of metastatic disease at the time of surgery. Mean tumor diameter was 4.4 cm. All the lesions were solid and well circumscribed. Calcifications were not seen in any of these masses. Thirty-three percent of the tumors demonstrated a central stellate hypodensity pattern, whereas a further 42% of the tumors demonstrated a heterogenous appearance. Mean attenuation values were 25.7 HU (noncontrast), 77.4 HU (arterial), 124.8 HU (venous), and 76.8 HU (delayed). Tumor-to-cortex ratios for the 2 enhanced phases (arterial and venous) were 0.56 and 0.79, respectively. Conclusions A series of HOCTs were found on CT to have 2 distinct patterns-a heterogenous enhancement pattern and an "oncocytoma-like" pattern with a central stellate hypodensity. Although the prospective diagnosis of HOCTs on the basis of CT findings is unlikely, an awareness of the existence of these lesions is important as new means of characterizing renal masses on imaging arise.

The development of an iatrogenic vascular lesion, such a renal pseudoaneurysm or arteriovenous fistula, is a rare complication of partial nephrectomy. These lesions should be considered in patients presenting with an enhancing mass in the resection bed shortly following partial nephrectomy. Early timing following surgery, large relative size, and the presence of recurrent hematuria suggest the diagnosis of an iatrogenic vascular lesion. Duplex ultrasound is a useful non-invasive imaging modality for differentiating these lesions from a local tumor recurrence.

TPS5586 Background: Metastasis directed therapy (MDT) is able to prolong progression free survival (PFS) and forestall initiation of androgen deprivation therapy (ADT) in men with hormone-sensitive, oligometastatic prostate cancer (HSOPCa) compared to observation. While MDT appears to be effective in HSOPCa, a large percentage of men will have disease recurrence. Patterns of failure demonstrate patients tend to recur 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 Stereotactic ablative radiation (SABR) + radium-223 dichloride in prolonging PFS in men with HSOPCa. Methods: Patients with HSOPCa and 3 or less metastases with at least 1 bone metastasis (by conventional imaging) will be randomized 1:1 to SABR alone vs. SABR + radium-223 dichloride. Eligibility criteria include PSA doubling time of < 15 months and ECOG performance status of < 2. Patients cannot be on ADT and must have normal testosterone levels at the time of randomization. Patients randomized to the combination arm will receive six doses of Radium-223 dichloride at four week intervals. A sample size using a 1:1 randomization scheme of 30 patients per arm will provide 80% power to detect an increase of median PFS from 10 months to 20 months with type I error = 0.1, using a one-sided log-rank test. To account for 5% early drop out, we will randomize a total of 64 patients (32 per arm). The primary end point is PFS with a primary hypothesis that SABR + radium-223 dichloride will increase median PFS from 10 months in the SABR arm to 20 months in the SABR + radium-223 dichloride arm. Progression is a composite endpoint including PSA progression per Prostate Cancer Working Group 2 (PCWG2), symptomatic progression, radiologic progression per RECIST 1.1 criteria, initiation of ADT, or death due to any cause. 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. Biological correlates will be evaluated including changes in circulating tumor cells following therapy, deep sequencing of circulating tumor DNA, and T-cell repertoire profiling before and after therapy. Clinical trial information: NCT04037358 .

Importance Complete metastatic ablation of oligometastatic prostate cancer may provide an alternative to early initiation of androgen deprivation therapy (ADT). Objective To determine if stereotactic ablative radiotherapy (SABR) improves oncologic outcomes in men with oligometastatic prostate cancer. Design, Setting, and Participants The Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) phase 2 randomized study accrued participants from 3 US radiation treatment facilities affiliated with a university hospital from May 2016 to March 2018 with a data cutoff date of May 20, 2019, for analysis. Of 80 men screened, 54 men with recurrent hormone-sensitive prostate cancer and 1 to 3 metastases detectable by conventional imaging who had not received ADT within 6 months of enrollment or 3 or more years total were randomized. Interventions Patients were randomized in a 2:1 ratio to receive SABR or observation. Main Outcomes and Measures The primary outcome was progression at 6 months by prostate-specific antigen level increase, progression detected by conventional imaging, symptomatic progression, ADT initiation for any reason, or death. Predefined secondary outcomes were toxic effects of SABR, local control at 6 months with SABR, progression-free survival, Brief Pain Inventory (Short Form)–measured quality of life, and concordance between conventional imaging and prostate-specific membrane antigen (PSMA)–targeted positron emission tomography in the identification of metastatic disease. Results In the 54 men randomized, the median (range) age was 68 (61-70) years for patients allocated to SABR and 68 (64-76) years for those allocated to observation. Progression at 6 months occurred in 7 of 36 patients (19%) receiving SABR and 11 of 18 patients (61%) undergoing observation (P = .005). Treatment with SABR improved median progression-free survival (not reached vs 5.8 months; hazard ratio, 0.30; 95% CI, 0.11-0.81;P = .002). Total consolidation of PSMA radiotracer-avid disease decreased the risk of new lesions at 6 months (16% vs 63%;P = .006). No toxic effects of grade 3 or greater were observed. T-cell receptor sequencing identified significant increased clonotypic expansion following SABR and correlation between baseline clonality and progression with SABR only (0.082085 vs 0.026051;P = .03). Conclusions and Relevance Treatment with SABR for oligometastatic prostate cancer improved outcomes and was enhanced by total consolidation of disease identified by PSMA-targeted positron emission tomography. SABR induced a systemic immune response, and baseline immune phenotype and tumor mutation status may predict the benefit from SABR. These results underline the importance of prospective randomized investigation of the oligometastatic state with integrated imaging and biological correlates. Trial Registration ClinicalTrials.gov Identifier:NCT02680587

9 Background: Current imaging modalities are suboptimal for the initial staging of men at risk of harboring occult metastatic prostate cancer (PCa). PSMA-based imaging is considered highly promising for PCa detection. 18F-DCFPyL is a novel PSMA-targeted radiopharmaceutical for positron emission tomography (PET) that may be useful in staging of pts with high risk PCa. The diagnostic performance of 18F-DCFPyL regarding regional and distant metastases has been previously reported. Here we report on detection rates and the resulting impact 18F-DCFPyL may have on staging of pts with high risk PCa. Methods: 18F-DCFPyL PET/CT was evaluated in 252 men with high-risk PCa who were planned for radical prostatectomy with lymphadenectomy (RP-PLND). 9 mCi (333 MBq) of 18F-DCFPyL was administered 1-2 hours prior to PET/CT. Based on TNM staging, 18F-DCFPyL PET/CT detection rates including lesion counts were systematically analyzed: prostatic (T), pelvic LN (N), extra-pelvic LN (M1a), bone (M1b) & other visceral organs/soft tissue (M1c). Three central, blinded, and independent readers evaluated the 18F-DCFPyL scans. Results: At study entry, 97% and 99% of all evaluable pts had no known nodal or metastatic disease, respectively, based on standard cross-sectional imaging. Of these, 18F-DCFPyL PET/CT staged 37 (14.7%) pts with N1 disease and 27 (10.7%) pts with M1 disease (1 [0.4%] M1a, 23 [9.1%] M1b, and 3 [1.2%] M1c). In total, 56 (22%) of patients were upstaged to N1 or M1 disease by 18F-DCFPyL. The positive predictive value of 18F-DCFPyL based on histopathologic validation for pelvic LNs was 86.7% (95% CI: 70, 95). Only one patient in Cohort A underwent a biopsy of their 18F-DCFPyL detected M1 finding; histopathology confirmed the metastatic lesion in the spine to be a true positive. Conclusions: A total of 22% of pts with high-risk PCa planned for RP-PLND had regional or distant metastatic lesions detected on 18F-DCFPyL PET/CT. These results suggest the potential utility of 18F-DCFPyL PET/CT in the staging of men with newly diagnosed high risk PCa to develop optimized treatment paradigms. Clinical trial information: NCT02981368.

The aim of the present study was to evaluate the incidence of undiagnosed pulmonary arterial dilatation using the gated computed tomography (CT) images acquired in patients with an otherwise normal Tc-sestamibi single-photon-emission CT (SPECT)/CT myocardial perfusion study.This was a retrospective review of 200 consecutive patients (100 men, mean age 58.7 years) who underwent a myocardial perfusion Tc-sestamibi SPECT/CT study with normal perfusion and with gated CT images acquired for coronary calcium scoring. The CT images were reviewed using a previously validated mean main pulmonary artery diameter (mPAD) measurement method which has been correlated with pulmonary arterial hypertension (PAH). Clinical information on multiple comorbidities was also retrieved. Previously reported mPAD cutoffs (29.5 and31.5 mm) were used to stratify patients.Indications for the study included dyspnea on exertion (58.9%), preoperative workup (22.3%), and chest pain (13.9%). The mean mPAD measurement was 26.3 mm (±0.5). There was a significant correlation between body mass index and mPAD (correlation coefficient [ρ]: 0.28; P .001). About 23% (46/200) of patients had mPAD 29.5 mm and 15.0% (30/200) of patients had mPAD 31.5 mm. From previous work, these cutoffs have a sensitivity and specificity for PAH of 70.8%, 79.4% and 52.0%, 90.2%, respectively. Among patients undergoing a preoperative myocardial perfusion study, 35.6% (16/45) patients had mPAD29.5 mm and 26.7% (12/45) patients had mPAD31.5 mm. There was a higher prevalence of congestive heart failure (62.5% vs 19.6%; P .001) and hypertension (78.3% vs 21.7%; P .02) in patients with mPAD29.5 mm. Similarly, there was a high prevalence of congestive heart failure (P .001), hyperlipidemia (P .04), and hypertension (P .04) in patients with mPAD31.5 mm.Incidental pulmonary arterial dilatation (mPAD ≥ 29.5 mm) can be detected in a large number of patients with normal myocardial perfusion scintigraphy and correlates with multiple different comorbidities. The mPAD can be measured in all patients undergoing gated imaging as part of a myocardial perfusion study, and PAH may be considered as an alternative explanation for symptoms in some patients without perfusion deficits. The data to make this potential diagnosis is already being acquired and represents an opportunity to add value to the interpretations of otherwise negative myocardial perfusion studies.

Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)–targeted PET imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of (18)F-DCFPyL (2-(3-{1-carboxy-5-[(6-(18)F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) PET examinations in a prospective setting mimicking the typical clinical workflow at a prostate cancer referral center. Methods: Four readers (2 experienced readers (ERs, >3 y of PSMA-targeted PET interpretation experience) and 2 inexperienced readers (IRs

Purpose The metabolically most active lesion in 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic 18F-FDG PET. Methods Eighteen patients with progressive MTC underwent baseline 18F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated. Results The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3 y (vs. low-risk group, OS = 5.3 y, 8/18, AUC = 0.78, P = 0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS = 3.5 y vs. low-risk group, OS = 5 y, 7/18, AUC = 0.83, P = 0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P = 0.02, OS, n.s.). Conclusions The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.

Evaluation of stomach neoplasms by traditional 3-dimensional (3D) computed tomography methods such as volume rendering and maximum-intensity projection plays an important role in lesion detection and characterization, preoperative planning, staging, and follow-up. Recently, a new 3D visualization method has become available known as cinematic rendering (CR). This novel technique makes use of a complex global lighting model to impart photorealistic levels of detail to 3D images. Although this new technique has yet to be systematically studied for the evaluation of stomach neoplasms, its intrinsic ability to create realistic shadowing effects to enhance understanding of the 3D relative locations of anatomic structures and to enhance detail and texture may prove valuable for a variety of applications. In this article, we demonstrate the CR appearance of multiple different gastric neoplasms, describe potential advantages of CR, and suggest future research directions.

3D computed tomography (CT) visualizations of volumetric data have become an important aspect of diagnostic imaging. The utility of 3D CT has been well described for the imaging of a number of renal pathologies. Recently, a new 3D visualization technique known as cinematic rendering (CR) has become available and provides photorealistic images derived from standard CT acquisitions by use of a complex global lighting model. Herein, we describe a number of normal variant and pathologic conditions of the kidney visualized with CR. We provide comparisons of findings with CR to traditional methods of 3D imaging and comment on the potential applications of this new method of 3D CT rendering.

Mycotic aneurysms are uncommon but emergent conditions in which infection of a vessel leads to a contained rupture. Progression to frank rupture, thrombosis, distal embolization, and death can occur. The widespread availability of computed tomography (CT) and its ability to obtain high-resolution, contrast-enhanced, volumetric images rapidly has made it the modality of choice for evaluating mycotic aneurysms. Three-dimensional CT visualizations can provide important information to surgeons and interventionalists prior to attempting repair of these lesions. In this case series, we demonstrate the appearance of mycotic aneurysms with the novel 3D CT visualization methodology known as cinematic rendering (CR). CR makes use of a more complex lighting model than has previously been utilized with other 3D CT techniques, allowing for enhanced surface detail and realistic shadowing effects. These features of CR may have utility in evaluating mycotic aneurysms and in pre-procedural/pre-operative planning, although a prospective study definitively evaluating this has not yet been performed.

Prostate-specific membrane antigen (PSMA), a type-II integral membrane protein highly expressed in prostate cancer, has been extensively used as a target for imaging and therapy. Among the available PET radiotracers, the low molecular weight agents that bind to PSMA are proving particularly effective. We present the dosimetry results for 18F-DCFPyL in nine patients with metastatic prostate cancer. Nine patients were imaged using sequential PET/CT scans at approximately 1, 12, 35 and 70 min, and a final PET/CT scan at approximately 120 min after intravenous administration of 321 ± 8 MBq (8.7 ± 0.2 mCi) of18F-DCFPyL. Time-integrated-activity coefficients were calculated and used as input in OLINDA/EXM software to obtain dose estimates for the majority of the major organs. The absorbed doses (AD) to the eye lens and lacrimal glands were calculated using Monte-Carlo models based on idealized anatomy combined with patient-specific volumes and activity from the PET/CT scans. Monte-Carlo based models were also developed for calculation of the dose to two major salivary glands (parotid and submandibular) using CT-based patient-specific gland volumes. The highest calculated mean AD per unit administered activity of 18F was found in the lacrimal glands, followed by the submandibular glands, kidneys, urinary bladder wall, and parotid glands. The S-values for the lacrimal glands to the eye lens (0.42 mGy/MBq h), the tear film to the eye lens (1.78 mGy/MBq h) and the lacrimal gland self-dose (574.10 mGy/MBq h) were calculated. Average S-values for the salivary glands were 3.58 mGy/MBq h for the parotid self-dose and 6.78 mGy/MBq h for the submandibular self-dose. The resultant mean effective dose of 18F-DCFPyL was 0.017 ± 0.002 mSv/MBq. 18F-DCFPyL dosimetry in nine patients was obtained using novel models for the lacrimal and salivary glands, two organs with potentially dose-limiting uptake for therapy and diagnosis which lacked pre-existing models.

A 71-year-old man with castration-resistant prostate cancer demonstrated a flare phenomenon on Tc-MDP and CT after 10 weeks of enzalutamide. Prostate-specific membrane antigen-targeted F-DCFPyL PET/CT demonstrated minimal uptake at sites of baseline bone and lymph node disease with increasing uptake at sites of osseous disease following therapy. Although this is likely related in part to decreased androgen receptor activity and a consequent increase in prostate-specific membrane antigen expression, other mechanisms (neovascularization, cell infiltration from the bone repair process, osteoblastic turnover, or minimal radiotracer impurity) may also be involved in causing the increased F-DCFPyL uptake at sites of osseous flare.