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Objective: To assess impact of image quality on prostate cancer extraprostatic extension (EPE) detection on MRI using a deep learning-based AI algorithm. Materials and methods: This retrospective, single institution study included patients who were imaged with mpMRI and subsequently underwent radical prostatectomy from June 2007 to August 2022. One genitourinary radiologist prospectively evaluated each patient using the NCI EPE grading system. Each T2WI was classified as low- or high-quality by a previously developed AI algorithm. Fisher's exact tests were performed to compare EPE detection metrics between low- and high-quality images. Univariable and multivariable analyses were conducted to assess the predictive value of image quality for pathological EPE. Results: A total of 773 consecutive patients (median age 61 [IQR 56–67] years) were evaluated. At radical prostatectomy, 23% (180/773) of patients had EPE at pathology, and 41% (131/318) of positive EPE calls on mpMRI were confirmed to have EPE. The AI algorithm classified 36% (280/773) of T2WIs as low-quality and 64% (493/773) as high-quality. For EPE grade ≥ 1, high-quality T2WI significantly improved specificity for EPE detection (72% [95% CI 67–76%] vs. 63% [95% CI 56–69%], P = 0.03), but did not significantly affect sensitivity (72% [95% CI 62–80%] vs. 75% [95% CI 63–85%]), positive predictive value (44% [95% CI 39–49%] vs. 38% [95% CI 32–43%]), or negative predictive value (89% [95% CI 86–92%] vs. 89% [95% CI 85–93%]). Sensitivity, specificity, PPV, and NPV for EPE grades ≥ 2 and ≥ 3 did not show significant differences attributable to imaging quality. For NCI EPE grade 1, high-quality images (OR 3.05, 95% CI 1.54–5.86; P < 0.001) demonstrated a stronger association with pathologic EPE than low-quality images (OR 1.76, 95% CI 0.63–4.24; P = 0.24). Conclusion: Our study successfully employed a deep learning-based AI algorithm to classify image quality of prostate MRI and demonstrated that better quality T2WI was associated with more accurate prediction of EPE at final pathology. [ABSTRACT FROM AUTHOR]

Near infrared photoimmunotherapy (NIR-PIT) is a recently approved cancer therapy for recurrent head and neck cancer. It involves the intravenous administration of an antibody-photoabsorber (IRDye700DX: IR700) conjugate (APC) to target cancer cells, followed 24 h later by exposure to near infrared light to activate cell-specific cytotoxicity. NIR-PIT selectively targets cancer cells for destruction and activates a strong anticancer host immunity. The fluorescent signal emitted by IR700 enables the visualization of the APC in vivo using fluorescence imaging. Similarly, the activation of IR700 during therapy can be monitored by loss of fluorescence. NIR-PIT can be used with a variety of antibodies and therefore, a variety of cancer types. However, in most cases, NIR-PIT requires direct light exposure only achieved with interstitial diffuser light fibers that are placed with image-guided interventional needle insertion. In addition, the unique nature of NIR-PIT cell death, means that metabolic molecular imaging techniques such as PET and diffusion MRI can be used to assess therapeutic outcomes. This mini-review focuses on the potential implications of NIR-PIT for interventional radiology and therapeutic monitoring. [ABSTRACT FROM AUTHOR]

Background: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a critical role in tumor immunosuppression. However, targeted depletion of CAFs is difficult due to their diverse cells of origin and the resulting lack of specific surface markers. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that leads to rapid cell membrane damage. Methods: In this study, we used anti-mouse fibroblast activation protein (FAP) antibody to target FAP+ CAFs (FAP-targeted NIR-PIT) and investigated whether this therapy could suppress tumor progression and improve tumor immunity. Results: FAP-targeted NIR-PIT induced specific cell death in CAFs without damaging adjacent normal cells. Furthermore, FAP-targeted NIR-PIT treated mice showed significant tumor regression in the CAF-rich tumor model accompanied by an increase in CD8+ tumor infiltrating lymphocytes (TILs). Moreover, treated tumors showed increased levels of IFN-γ, TNF-α, and IL-2 in CD8+ TILs compared with non-treated tumors, suggesting enhanced antitumor immunity. Conclusions: Cancers with FAP-positive CAFs in their TME grow rapidly and FAP-targeted NIR-PIT not only suppresses their growth but improves tumor immunosuppression. Thus, FAP-targeted NIR-PIT is a potential therapeutic strategy for selectively targeting the TME of CAF+ tumors. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the cancer detection rates of reduced-core biopsy schemes in patients with unilateral mpMRI-visible intraprostatic lesions and to analyze the contribution of systematic biopsy cores in clinically significant prostate cancer (csPCa) detection. Methods: 212 patients with mpMRI-visible unilateral intraprostatic lesions undergoing MRI/TRUS fusion-guided targeted biopsy (TBx) and systematic biopsy (SBx) were included. Cancer detection rates of TBx + SBx, as determined by highest Gleason Grade Group (GG), were compared to 3 reduced-core biopsy schemes: TBx alone, TBx + ipsilateral systematic biopsy (IBx; MRI-positive hemigland), and TBx + contralateral systematic biopsy (CBx; MRI-negative hemigland). Patient-level and biopsy core-level data were analyzed using descriptive statistics with confidence intervals. Univariable and multivariable logistic regression analysis was conducted to identify predictors of csPCa (≥ GG2) detected in MRI-negative hemiglands at p < 0.05. Results: Overall, 43.4% (92/212) of patients had csPCa and 66.0% (140/212) of patients had any PCa detected by TBx + SBx. Of patients with csPCa, 81.5% had exclusively ipsilateral involvement (MRI-positive), 7.6% had only contralateral involvement (MRI-negative), and 10.9% had bilateral involvement. The csPCa detection rates of reduced-core biopsy schemes were 35.4% (75/212), 40.1% (85/212), and 39.6% (84/212) for TBx alone, TBx + IBx, and TBx + CBx, respectively, with detection sensitivities of 81.5%, 92.4%, and 91.3% compared to TBx + SBx. Conclusion: Reduced-core prostate biopsy strategies confined to the ipsilateral hemigland underestimate csPCa burden by at least 8% in patients with unilateral mpMRI-visible intraprostatic lesions. The combined TBx + SBx strategy maximizes csPCa detection. [ABSTRACT FROM AUTHOR]

Near-infrared photoimmunotherapy (NIR-PIT) selectively kills tumor cells to which the photo-absorber dye IR700DX-conjugated antibodies are bound and induces a systemic anti-tumor immune response. NIR-PIT induces immunogenic cell death (ICD), releases damage-associated molecular patterns (DAMPs) molecules from dying tumor cells, and activates dendritic cells (DCs). However, it is unclear whether NIR-PIT affects migration of tumor-infiltrating (Ti)-DCs to draining lymph nodes (dLNs), where a systemic anti-tumor response is induced. Here, we utilized in vivo photolabeling of Ti-DCs in tumors in photoconvertible protein Kikume Green-Red (KikGR) mice to show that NIR-PIT enhanced migration of Ti-DCs including cDC1s, cDC2s, and CD326+ DCs to dLNs. This effect was abolished by blocking adenosine triphosphate (ATP), one of the DAMPs molecules, as well as by inhibition of Gαi signaling by pertussis toxin. Thus, ICD induction by NIR-PIT stimulates Ti-DC migration to dLNs via ATP-P2X7 receptor and Gαi protein-coupled receptor signaling pathways and may augment tumor antigen presentation to induce anti-tumor T cells in dLNs. [ABSTRACT FROM AUTHOR]

V-domain immunoglobulin suppressor of T cell activation (VISTA) is an inhibitory immune checkpoint molecule that is broadly expressed on lymphoid and myeloid cells, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Near-infrared photoimmunotherapy (NIR-PIT) is a cancer treatment that utilizes an antibody-photoabsorber (IRDye 700DX NHS ester) conjugate to selectively kill target cells after the local application of NIR light. Depletion of VISTA-expressing cells in the tumor microenvironment (TME) using NIR-PIT could enhance anti-tumor immune responses by removing immune suppressive cells. The purpose of this study was to evaluate the anti-tumor efficacy of VISTA-targeted NIR-PIT using two murine tumor models, MC38-luc and LL2-luc. VISTA was expressed on T cells including Tregs and MDSCs in the TME of these tumors. In contrast, CD45 − cells, including cancer cells, did not express VISTA. VISTA-targeted NIR-PIT depleted VISTA-expressing cells ex vivo. In vivo VISTA-targeted NIR-PIT inhibited tumor progression and prolonged survival in both models. After VISTA-targeted NIR-PIT, augmented CD8 + T cell and dendritic cell activation were observed in regional lymph nodes. In conclusion, VISTA-targeted NIR-PIT can effectively treat tumors by decreasing VISTA-expressing immune suppressor cells in the TME. Local depletion of VISTA-expressing cells in the tumor bed using NIR-PIT is a promising new cancer immunotherapy for treating various types of tumors. [ABSTRACT FROM AUTHOR]

Near-infrared photoimmunotherapy (NIR-PIT) is a cell-specific cancer therapy that uses an antibody-photoabsorber (IRDye700DX, IR700) conjugate (APC) and NIR light. Intravenously injected APC binds the target cells, and subsequent NIR light exposure induces immunogenic cell death only in targeted cells. Panitumumab and cetuximab are antibodies that target human epidermal growth factor receptor (hEGFR) and are suitable for NIR-PIT. In athymic nude mouse models, panitumumab-based NIR-PIT showed superior therapeutic efficacy compared to cetuximab-based NIR-PIT because of the longer half-life of panitumumab-IR700 (pan-IR700) compared with cetuximab-IR700 (cet-IR700). Two light exposures on two consecutive days have also been shown to induce superior effects compared to a single light exposure in the athymic nude mouse model. However, the optimal regimen has not been assessed in immunocompetent mice. In this study, we compared panitumumab and cetuximab in APCs for NIR-PIT, and single and double light exposures using a newly established hEGFR-expressing cancer cell line derived from immunocompetent C57BL/6 mice (mEERL-hEGFR cell line). Fluorescence imaging showed that the decline of pan-IR700 was slower than cet-IR700 confirming a longer clearance time. Among all the combinations tested, mice receiving pan-IR700 and double light exposure showed the greatest tumor growth inhibition. This group was also shown to activate CD8+ T lymphocytes in lymph nodes and accumulate CD8+ T lymphocytes to a greater extent within the tumor compared with the control group. These results showed that APCs with longer half-life and double light exposure lead to superior outcomes in cancer cell-targeted NIR-PIT in an immunocompetent mouse model. [ABSTRACT FROM AUTHOR]

Labeling immune cells with zirconium-89 (89Zr)-oxine has become a viable method to track cells in vivo by PET in various pre-clinical animal models and in clinical applications. Currently, 89Zr-oxine cell labeling is performed manually, which requires a highly trained specialist and is prone to human error. As the first phase in developing a fully automated radiolabeling system to address this problem, we assess the use of acoustophoresis cell washing to replace the centrifugal cell washing used in the current 89Zr-oxine cell radiolabeling procedure. To accomplish this, a cell radiolabeling procedure was developed in which two steps requiring a centrifuge to wash cells were replaced using acoustophoresis cell washing methods. The process was tested using murine EL4 lymphoma and T cells. The centrifuge cell labeling procedure was used as a control to compare the acoustophoresis cell washing procedure. The acoustophoresis method produced radiolabeled cells with similar properties to the centrifugal method when comparing labeling efficiency, labeled specific activity, efficacy of removing unbound 89Zr-oxine from the suspension, cell viability measured using annexin V/propidium iodide staining and activation function. This suggests that acoustophoresis cell washing can be used in the design of an automated benchtop, good manufacture practice-qualified acoustophoresis cell radiolabeling device. [ABSTRACT FROM AUTHOR]

In the past decades, immunotherapies against cancers made impressive progress. Immunotherapy includes a broad range of interventions that can be separated into two major groups: cell-based immunotherapies, such as adoptive T cell therapies and stem cell therapies, and immunomodulatory molecular therapies such as checkpoint inhibitors and cytokine therapies. Genetic engineering techniques that transduce T cells with a cancer-antigen-specific T cell receptor or chimeric antigen receptor have expanded to other cell types, and further modulation of the cells to enhance cancer targeting properties has been explored. Because cell-based immunotherapies rely on cells migrating to target organs or tissues, there is a growing interest in imaging technologies that non-invasively monitor transferred cells in vivo. Here, we review whole-body imaging methods to assess cell-based immunotherapy using a variety of examples. Following a review of preclinically used cell tracking technologies, we consider the status of their clinical translation. [ABSTRACT FROM AUTHOR]

Purpose: To present fully automated DL-based prostate cancer detection system for prostate MRI. Methods: MRI scans from two institutions, were used for algorithm training, validation, testing. MRI-visible lesions were contoured by an experienced radiologist. All lesions were biopsied using MRI-TRUS-guidance. Lesions masks, histopathological results were used as ground truth labels to train UNet, AH-Net architectures for prostate cancer lesion detection, segmentation. Algorithm was trained to detect any prostate cancer ≥ ISUP1. Detection sensitivity, positive predictive values, mean number of false positive lesions per patient were used as performance metrics. Results: 525 patients were included for training, validation, testing of the algorithm. Dataset was split into training (n = 368, 70%), validation (n = 79, 15%), test (n = 78, 15%) cohorts. Dice coefficients in training, validation sets were 0.403, 0.307, respectively, for AHNet model compared to 0.372, 0.287, respectively, for UNet model. In validation set, detection sensitivity was 70.9%, PPV was 35.5%, mean number of false positive lesions/patient was 1.41 (range 0–6) for UNet model compared to 74.4% detection sensitivity, 47.8% PPV, mean number of false positive lesions/patient was 0.87 (range 0–5) for AHNet model. In test set, detection sensitivity for UNet was 72.8% compared to 63.0% for AHNet, mean number of false positive lesions/patient was 1.90 (range 0–7), 1.40 (range 0–6) in UNet, AHNet models, respectively. Conclusion: We developed a DL-based AI approach which predicts prostate cancer lesions at biparametric MRI with reasonable performance metrics. While false positive lesion calls remain as a challenge of AI-assisted detection algorithms, this system can be utilized as an adjunct tool by radiologists. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this retrospective analysis is to estimate the most appropriate single cycle and cumulative doses of 225Ac-DOTATOC in patients treated for somatostatin-receptor-expressing cancers. Methods: 225Ac-DOTATOC was administered to thirty-nine patients with various somatostatin-receptor-positive tumors. Baseline and follow-up 68Ga-DOTATOC PET/CT, lab tests, and renal scintigraphy were obtained. Patients received long-term follow-up either at the local cancer center or in close collaboration with external oncologists. Acute and chronic hematological toxicity was evaluated quantitatively over time. Long-term follow-up of creatinine was used to approximate the annual loss of estimated GFR (eGFR). Results: Dose-dependent acute hematological toxicity was seen at single doses above 40 MBq or repeated doses greater than approximately 20 MBq 225Ac-DOTATOC at 4 month intervals. Treatment-related kidney failure occurred in 2 patients after a delay of >4 years but was independent of administered radioactivity, and other clinical risk factors were important contributors to renal decline. In general, the annual decline of eGFR among patients did not follow a clear dose-effect relationship even in patients with previous β-therapy. An average eGFR-loss of 8.4ml/min (9.9%) per year was observed which is similar to the experience with β-therapy studies. Conclusion: Treatment activities of approx. 20 MBq per cycle (4 monthly repetition) and cumulative doses up to 60–80 MBq generally avoided both acute and chronic grade 3/4 hematotoxicity in patients with advanced stage malignancies. Chronic renal toxicity was observed at these doses, but pre-existing renal risk factors were important co-factors. These data represent a starting point for additional research to more precisely define safety thresholds of 225Ac-DOTATOC. [ABSTRACT FROM AUTHOR]

Although low risk localised prostate cancer has an excellent prognosis owing to effective treatments, such as surgery, radiation, cryosurgery and hormone therapy, metastatic prostate cancer remains incurable. Existing therapeutic regimens prolong life; however, they are beset by problems of resistance, resulting in poor outcomes. Treatment resistance arises primarily from tumour heterogeneity, altered genetic signatures and metabolic reprogramming, all of which enable the tumour to serially adapt to drugs during the course of treatment. In this review, we focus on alterations in the metabolism of prostate cancer, including genetic signatures and molecular pathways associated with metabolic reprogramming. Advances in our understanding of prostate cancer metabolism might help to explain many of the adaptive responses that are induced by therapy, which might, in turn, lead to the attainment of more durable therapeutic responses. [ABSTRACT FROM AUTHOR]

Purpose: PSMA overexpression has been associated with aggressive prostate cancer (PCa). However, PSMA PET imaging has revealed highly variable changes in PSMA expression in response to ADT treatment ranging from increases to moderate decreases. To better understand these PSMA responses and potential relationship to progressive PCa, the PET imaging agent, [18F]DCFPyL, was used to assess changes in PSMA expression in response to ADT using genomically characterized LuCaP patient-derived xenograft mouse models (LuCaP-PDXs) which were found to be sensitive to ADT (LuCaP73 and LuCaP136;CS) or resistant (LuCaP167;CR). Methods: [18F]DCFPyL (2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) was used to assess PSMA in vitro (saturation assays) in LuCaP tumor membrane homogenates and in vivo (imaging/biodistribution) in LuCaP-PDXs. Control and ADT-treated LuCaPs were imaged before ADT (0 days) and 2-, 7-, 14-, and 21-days post-ADT from which tumor:muscle ratios (T:Ms) were determined and concurrently tumor volumes were measured (caliper). After the 21-day imaging, biodistributions and histologic/genomic (PSMA, AR) analysis were done. Results: [18F]DCFPyL exhibited high affinity for PSMA and distinguished different levels of PSMA in LuCaP tumors. Post-ADT CS LuCaP73 and LuCaP136 tumor volumes significantly decreased at day 7 or 14 respectively vs controls, whereas the CR LuCaP167 tumor volumes were minimally changed. [18F]DCFPyL imaging T:Ms were increased 3–5-fold in treated LuCaP73 tumors vs controls, while treated LuCaP136 T:Ms remained unchanged which was confirmed by day 21 biodistribution results. For treated LuCaP167, T:Ms were decreased (~ 45 %) vs controls but due to low T:M values (<2) may not be indicative of PSMA level changes. LuCaP73 tumor PSMA histologic/genomic results were comparable to imaging/biodistribution results, whereas the results for other tumor types varied. Conclusion: Tumor responses to ADT varied from sensitive to resistant among these LuCaP PDXs, while only the high PSMA expressing LuCaP model exhibited an increase in PSMA levels in response to ADT. These models may be useful in understanding the clinical relevance of PSMA PET responses to ADT and potentially the relationship to disease progression as it may relate to the genomic signature. [ABSTRACT FROM AUTHOR]

Background: PSMA-targeted radionuclide therapy (TRT) is a promising treatment for prostate cancer (PCa), but dose-limiting xerostomia can severely limit its clinical adaptation, especially when using alpha-emitting radionuclides. With [18F]DCFPyL as a surrogate for PSMA-TRT, we report a novel method to selectively reduce salivary gland (SG) uptake of systemically administered [18F]DCFPyL by immediate prior infusion of non-radioactive standard of [18F]DCFPyL (DCFPyL) directly into the SG via retrograde cannulation. Methods: A dose-finding cohort using athymic nude mice demonstrated proof of principle that SG uptake can be selectively blocked by DCFPyL administered either locally via cannulation (CAN group) or systemically (SYS group). The experiments were repeated in a validation cohort of 22RV1 tumor-bearing mice. Submandibular glands (SMG) of CAN mice were locally blocked with either saline or DCFPyL (dose range: 0.01× to 1000× molar equivalent of the radioactive [18F]DCFPyL dose). The radioactive dose of [18F]DCFPyL was administered systemically 10 min later and the mice euthanized after 1 h for biodistribution studies. Toxicity studies were done at up to 1000× dose. Results: In the dose-finding cohort, the SYS group showed a dose-dependent 12–40% decrease in both the SMG T/B and the kidney (tumor surrogate). Mild blocking was observed at 0.01× , with maximal blocking reached at 1× with no additional blocking up to 1000×. In the CAN group, blocking at the 0.1× and 1× dose levels resulted in a similar 42–53% decrease, but without the corresponding decrease in kidney uptake as seen in the SYS group. Some evidence of "leakage" of DCFPyL from the salivary gland into the systemic circulation was observed. However, experiments in 22RV1 tumor-bearing mice at the 0.1× and 1× dose levels confirm that, at the appropriate blocking dose, SG uptake of [18F]DCFPyL can be selectively reduced without affecting tumor uptake and with no toxicity. Conclusion: Our results suggest that direct retrograde instillation of DCFPyL into the SG could predictably and selectively decrease salivary uptake of systemically administered [18F]DCFPyL without altering tumor uptake, if given at the appropriate dose. This novel approach is easily translatable to clinical practice and has the potential to mitigate xerostomia, without compromising the therapeutic efficacy of the PSMA-TRT. [ABSTRACT FROM AUTHOR]

Drastic sensitivity enhancement of dynamic nuclear polarization is becoming an increasingly critical methodology to monitor real-time metabolic and physiological information in chemistry, biochemistry, and biomedicine. However, the limited number of available hyperpolarized 13C probes, which can effectively interrogate crucial metabolic activities, remains one of the major bottlenecks in this growing field. Here, we demonstrate [1-13C] N-acetyl cysteine (NAC) as a novel probe for hyperpolarized 13C MRI to monitor glutathione redox chemistry, which plays a central part of metabolic chemistry and strongly influences various therapies. NAC forms a disulfide bond in the presence of reduced glutathione, which generates a spectroscopically detectable product that is separated from the main peak by a 1.5 ppm shift. In vivo hyperpolarized MRI in mice revealed that NAC was broadly distributed throughout the body including the brain. Its biochemical transformation in two human pancreatic tumor cells in vitro and as xenografts differed depending on the individual cellular biochemical profile and microenvironment in vivo. Hyperpolarized NAC can be a promising non-invasive biomarker to monitor in vivo redox status and can be potentially translatable to clinical diagnosis. [ABSTRACT FROM AUTHOR]

OATP1B3 is expressed de novo in primary prostate cancer tissue and to a greater degree in prostate cancer metastases. Gadoxetate disodium is a substrate of OATP1B3, and its uptake has been shown to correlate with OATP1B3 expression in other cancers. We aimed to evaluate use of gadoxetate disodium to image prostate cancer and to track its utility as a biomarker. A single center open-label non-randomized pilot study recruited men with (1) localized, and (2) metastatic castration resistant prostate cancer (mCRPC). Gadoxetate disodium-enhanced MRI was performed at four timepoints post-injection. The Wilcoxon signed rank test was used to compare MRI contrast enhancement ratio (CER) pre-injection and post-injection. OATP1B3 expression was evaluated via immunohistochemistry (IHC) and a pharmacogenomic analysis of OATP1B3, NCTP and OATP1B1 was conducted. The mCRPC subgroup (n = 9) demonstrated significant enhancement compared to pre-contrast images at 20-, 40- and 60-min timepoints (p < 0.0078). The localized cancer subgroup (n = 11) demonstrated earlier enhancement compared to the mCRPC group, but no retention over time (p > 0.05). OATP1B3 expression on IHC trended higher contrast enhancement between 20–40 min (p ≤ 0.064) and was associated with contrast enhancement at 60 min (p = 0.0422). OATP1B1 haplotype, with N130D and V174A substitutions, impacted enhancement at 40–60 min (p ≤ 0.038). mCRPC lesions demonstrate enhancement after injection of gadoxetate disodium on MRI and retention over 60 min. As inter-individual variability in OATP1B3 expression and function has both predictive and prognostic significance, gadoxetate disodium has potential as a biomarker in prostate cancer. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of cleansing Fleet's™ enema (FE) on rectal distention and image quality of diffusion-weighted imaging (DWI) in prostate magnetic resonance imaging (MRI). Methods: This study included 117 prospectively accrued active surveillance patients who underwent prostate MRI both without (prep−) and with bowel preparation consisting of FE (prep+) obtained within 12 months of each other. The anterior–posterior (AP) diameter of the rectum, degree of perceived distention in the rectum and image quality scores were assessed by two independent readers for both (prep− and prep+) scans. DWI distortion was assessed quantitatively using the degree of anatomic mismatches between images obtained at different b values and the T2-weighted MRI. DWI artifact was qualitatively scored based on the presence of blurring, poor signal-to-noise, and artifact lines. The difference in rectal AP diameters between the two methods was tested by the paired Wilcoxon rank test. Stuart Maxell test was used in comparing rectal distention, DWI distortion, and artifact. Reader agreement was estimated by kappa statistics. p values < 0.05 were considered statistically significant. Results: Mean rectal AP diameter was significantly larger in prep− compared with prep+ scans (p = 0.002). Subjective scores demonstrated inter-reader variability. For instance, the rectal distention score was significantly lower in prep+ for reader 2 (p < 0.001) whereas it was not significant for reader 1 (p = 0.09). Reader 2 also found significant improvement in DWI distortion (p = 0.02) in prep+ scans. There was no significant difference between prep− and prep+ in DWI distortion and artifacts for reader 1 (p = 0.17 and p = 0.49, respectively), or DWI artifacts for reader 2 (p = 0.55). Kappa scores were moderate for rectal distension, but weak for DWI distortion, and artifacts. Conclusion: Bowel preparation with enema prior to prostate MRI may diminish rectal gas but has modest effects on DWI distortion and overall image quality. The value of bowel prep is not conclusively validated in this study. [ABSTRACT FROM AUTHOR]

Purpose: Apical periurethral transition zone (TZ) cancers can pose unique problems for surgery and radiation therapy. Here, we describe the appearance of such cancers on multiparametric MRI (mpMRI) and correlate this with histopathology derived from MRI-targeted biopsy. Materials and methods: Between May 2011 and January 2019, a total of 4381 consecutive patients underwent 3 T mpMRI. Of these, 53 patients with 58 apical periurethral TZ lesions underwent TRUS/MRI fusion-guided biopsy and 12-core systematic TRUS-guided biopsy. Correlation was made with patient age, PSA, PSA density, whole prostate volume, and Gleason scores. Results: A total 53 men (median age 68 years, median PSA 7.94 ng/ml) were identified as having at least one apical periurethral TZ lesion on mpMRI and 5 (9%) patients had more than one apical periurethral lesion. Thus, 58 lesions were identified in 53 patients. Of these 37/53 patients (69%) and 40/58 lesions were positive at biopsy for prostate cancer. Seven were diagnosed by 12-core systematic TRUS-guided biopsy and 34 were diagnosed by TRUS/MRI fusion-guided biopsy. Gleason score was ≥ 3 + 4 in 34/58 (58%) lesions. Conclusion: Identification of apical periurethral TZ prostate cancers is important to help guide surgical and radiation therapy as these tumors are adjacent to critical structures. Because of the tendency to undersample the periurethral zone during TRUS biopsy, MRI-guided biopsy is particularly helpful for detecting apical periurethral TZ prostate cancers many of which prove to be clinically significant. [ABSTRACT FROM AUTHOR]

Imaging plays an increasing role in prostate cancer diagnosis and staging. Accurate staging of prostate cancer is required for optimal treatment planning. In detecting extraprostatic cancer and sites of early recurrence, traditional imaging methods (computed tomography, magnetic resonance imaging, radionuclide bone scan) have suboptimal performance. This leaves a gap between known disease recurrence as indicated by rising prostate-specific antigen and the ability to localize the recurrence on imaging. Novel positron emission tomography (PET) agents including radiolabeled choline, fluciclovine (18F-FACBC), and agents targeting prostate-specific membrane antigen are being developed and tested to increase diagnostic performance of non-invasive prostate cancer localization. When combined with CT or MRI, these tracers offer a combination of functional information and anatomic localization that is superior to conventional imaging methods. These PET radiotracers have varying mechanisms and excretion patterns affecting their pharmacokinetics and diagnostic performance, which will be reviewed in this article. [ABSTRACT FROM AUTHOR]

Localized prostate cancers are genetically variable and frequently multifocal, comprising spatially distinct regions with multiple independently-evolving clones. To date there is no understanding of whether this variability can influence management decisions for patients with prostate tumors. Here, we present a single case from a clinical trial of neoadjuvant intense androgen deprivation therapy. A patient was diagnosed with a large semi-contiguous tumor by imaging, histologically composed of a large Gleason score 9 tumor with an adjacent Gleason score 7 nodule. DNA sequencing demonstrates these are two independent tumors, as only the Gleason 9 tumor harbors single-copy losses of PTEN and TP53. The PTEN/TP53-deficient tumor demonstrates treatment resistance, selecting for subclones with mutations to the remaining copies of PTEN and TP53, while the Gleason 7 PTEN-intact tumor is almost entirely ablated. These findings indicate that spatiogenetic variability is a major confounder for personalized treatment of patients with prostate cancer. Prostate cancer is often a multifocal disease but how best to manage this clinically remains unclear. Here, the authors report a single case study of a patient with two genetically diverse tumours which showed differential response to therapy. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the prognostic value of 18F-sodium fluoride (NaF) PET/CT in patients with urological malignancies treated with cabozantinib and nivolumab with or without ipilimumab. Methods: We prospectively recruited patients with advanced urological malignancies into a phase I trial of cabozantinib plus nivolumab with or without ipilimumab. NaF PET/CT scans were performed pre- and 8 weeks post-treatment. We measured the total volume of fluoride avid bone (FTV) using a standardized uptake value (SUV) threshold of 10. We used Kaplan-Meier analysis to predict the overall survival (OS) of patients in terms of SUVmax, FTV, total lesion fluoride (TLF) uptake at baseline and 8 weeks post-treatment, and percent change in FTV and TLF. Result: Of 111 patients who underwent NaF PET/CT, 30 had bone metastases at baseline. Four of the 30 patients survived for the duration of the study period. OS ranged from 0.23 to 34 months (m) (median 6.0 m). The baseline FTV of all 30 patients ranged from 9.6 to 1570 ml (median 439 ml). The FTV 8 weeks post-treatment was 56–6296 ml (median 448 ml) from 19 available patients. Patients with higher TLF at baseline had shorter OS than patients with lower TLF (3.4 vs 14 m; p = 0.022). Patients with higher SUVmax at follow-up had shorter OS than patients with lower SUVmax (5.6 vs 24 m; p = 0.010). However, FTV and TLF 8 weeks post-treatment did not show a significant difference between groups (5.6 vs 17 m; p = 0.49), and the percent changes in FTV (12 vs 14 m; p = 0.49) and TLF (5.6 vs 17 m; p = 0.54) also were not significant. Conclusion: Higher TLF at baseline and higher SUVmax at follow-up NaF PET/CT corresponded with shorter survival in patients with bone metastases from urological malignancies who underwent treatment. NaF PET/CT may be a useful predictor of OS in this population. [ABSTRACT FROM AUTHOR]

Radiomics and radiogenomics are attractive research topics in prostate cancer. Radiomics mainly focuses on extraction of quantitative information from medical imaging, whereas radiogenomics aims to correlate these imaging features to genomic data. The purpose of this review is to provide a brief overview summarizing recent progress in the application of radiomics-based approaches in prostate cancer and to discuss the potential role of radiogenomics in prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Peritoneal dissemination (PD) of abdominal malignancies is a common form of metastasis and its presence signals a poor prognosis. New treatment is required for patients with PD. Near infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody–photo-absorber conjugate (APC). In this study, we investigate in vitro and in vivo efficacy of trastuzumab (tra)-IR700DX NIR-PIT on a human epidermal growth factor receptor type 2 (HER2)-positive gastric cancer cell line. Methods: NIR-PIT effects were investigated in vitro and in vivo. Disseminated peritoneal implants mice were separated into 5 groups: (1) no treatment; (2) tra-IR700 i.v. only; (3) NIR light only; (4) NIR-PIT; (5) repeated NIR-PIT. The peritoneal cavity was irradiated with NIR light using a fiber optic diffuser delivered through the catheter. Results: Specific binding and cell-specific killing was observed after NIR-PIT in vitro. In the in vivo study, fluorescence endoscopy showed high tumor accumulation of tra-IR700 within tumors. Significantly prolonged survival was achieved in the three treatment groups (tra-IR700 i.v. only, NIR-PIT, and repeated NIR-PIT groups) compared with control and NIR light only group (p < 0.05 for tra-IR700 i.v. only, p < 0.01 for NIR-PIT, and p < 0.0001 for repeated NIR-PIT). Moreover, most prolonged survival was shown for the repeated NIR-PIT group (p < 0.0001 vs tra-IR700 i.v. only, p < 0.01 vs NIR-PIT). Conclusion: NIR-PIT using a fiber optic diffuser to deliver light is a promising candidate for the treatment of disseminated peritoneal metastases and could be readily translated to humans. [ABSTRACT FROM AUTHOR]

Introduction: Multiparametric magnetic resonance imaging (mpMRI) has improved clinicians' ability to detect clinically significant prostate cancer (csPCa). Combining or fusing these images with the real-time imaging of transrectal ultrasound (TRUS) allows urologists to better sample lesions with a targeted biopsy (Tbx) leading to the detection of greater rates of csPCa and decreased rates of low-risk PCa. In this review, we evaluate the technical aspects of the mpMRI-guided Tbx procedure to identify possible sources of error and provide clinical context to a negative Tbx.Methods: A literature search was conducted of possible reasons for false-negative TBx. This includes discussion on false-positive mpMRI findings, termed "PCa mimics," that may incorrectly suggest high likelihood of csPCa as well as errors during Tbx resulting in inexact image fusion or biopsy needle placement.Results: Despite the strong negative predictive value associated with Tbx, concerns of missed disease often remain, especially with MR-visible lesions. This raises questions about what to do next after a negative Tbx result. Potential sources of error can arise from each step in the targeted biopsy process ranging from "PCa mimics" or technical errors during mpMRI acquisition to failure to properly register MRI and TRUS images on a fusion biopsy platform to technical or anatomic limits on needle placement accuracy.Conclusions: A better understanding of these potential pitfalls in the mpMRI-guided Tbx procedure will aid interpretation of a negative Tbx, identify areas for improving technical proficiency, and improve both physician understanding of negative Tbx and patient-management options. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to determine if the ≥ 15 mm threshold currently used to define PIRADS 5 lesions is the optimal size threshold for predicting high likelihood of clinically significant (CS) cancers.Materials: Three hundred and fifty-eight lesions that may be changed from category 4 to 5 or vice versa on the basis of the size criterion (category 4: n = 288, category 5: n = 70) from 255 patients were evaluated. Kendall’s tau-b statistic accounting for inter-lesion correlation, generalized estimation equation logistic regression, and receiver operating curve analysis evaluated two lesion size-metrics (lesion diameter and relative lesion diameter—defined as lesion diameter/prostate volume) for ability to identify CS (Gleason grade ≥ 3 + 4) cancer at targeted biopsy. Optimal cut-points were identified using the Youden index. Analyses were performed for the whole prostate (WP) and zone-specific sub-cohorts of lesions in the peripheral and transition zones (PZ and TZ).Results: Lesion diameter showed a modest correlation with Gleason grade (WP: τB = 0.21, p < 0.0001; PZ: τB = 0.13, p = 0.02; TZ: τB = 0.32, p = 0.001), and association with CS cancer detection (WP: AUC = 0.63, PZ: AUC = 0.59, TZ: AUC = 0.74). Empirically derived thresholds (WP: 14 mm, PZ: 13 mm, TZ: 16 mm) performed similarly to the current ≥ 15 mm standard. Lesion relative lesion diameter improved identification of CS cancers compared to lesion diameter alone (WP: τB = 0.30, PZ: τB = 0.24, TZ: τB = 0.42, all p < 0.0001). AUC also improved for WP and PZ lesions (WP: AUC = 0.70, PZ: AUC = 0.68, and TZ: AUC = 0.74).Conclusions: The current ≥ 15 mm diameter threshold is a reasonable delineator of PI-RADS category 4 and category 5 lesions in the absence of extraprostatic extension to predict CS cancers. Additionally, relative lesion diameter can improve identification of CS cancers and may serve as another option for distinguishing category 4 and 5 lesions. [ABSTRACT FROM AUTHOR]

Purpose: We propose an approach of 3D convolutional neural network to segment the prostate in MR images.Methods: A 3D deep dense multi-path convolutional neural network that follows the framework of the encoder-decoder design is proposed. The encoder is built based upon densely connected layers that learn the high-level feature representation of the prostate. The decoder interprets the features and predicts the whole prostate volume by utilizing a residual layout and grouped convolution. A set of sub-volumes of MR images, centered at the prostate, is generated and fed into the proposed network for training purpose. The performance of the proposed network is compared to previously reported approaches.Results: Two independent datasets were employed to assess the proposed network. In quantitative evaluations, the proposed network achieved 95.11 and 89.01 Dice coefficients for the two datasets. The segmentation results were robust to variations in MR images. In comparison experiments, the segmentation performance of the proposed network was comparable to the previously reported approaches. In qualitative evaluations, the segmentation results by the proposed network were well matched to the ground truth provided by human experts.Conclusions: The proposed network is capable of segmenting the prostate in an accurate and robust manner. This approach can be applied to other types of medical images. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate if computer-aided diagnosis (CAD) prior to prostate multi-parametric MRI (mpMRI) can improve sensitivity and agreement between radiologists.Methods: Nine radiologists (three each high, intermediate, low experience) from eight institutions participated. A total of 163 patients with 3-T mpMRI from 4/2012 to 6/2015 were included: 110 cancer patients with prostatectomy after mpMRI, 53 patients with no lesions on mpMRI and negative TRUS-guided biopsy. Readers were blinded to all outcomes and detected lesions per PI-RADSv2 on mpMRI. After 5 weeks, readers re-evaluated patients using CAD to detect lesions. Prostatectomy specimens registered to MRI were ground truth with index lesions defined on pathology. Sensitivity, specificity and agreement were calculated per patient, lesion level and zone-peripheral (PZ) and transition (TZ).Results: Index lesion sensitivity was 78.2% for mpMRI alone and 86.3% for CAD-assisted mpMRI (p = 0.013). Sensitivity was comparable for TZ lesions (78.7% vs 78.1%; p = 0.929); CAD improved PZ lesion sensitivity (84% vs 94%; p = 0.003). Improved sensitivity came from lesions scored PI-RADS < 3 as index lesion sensitivity was comparable at PI-RADS ≥ 3 (77.6% vs 78.1%; p = 0.859). Per patient specificity was 57.1% for CAD and 70.4% for mpMRI (p = 0.003). CAD improved agreement between all readers (56.9% vs 71.8%; p < 0.001).Conclusions: CAD-assisted mpMRI improved sensitivity and agreement, but decreased specificity, between radiologists of varying experience.Key Points: • Computer-aided diagnosis (CAD) assists clinicians in detecting prostate cancer on MRI. • CAD assistance improves agreement between radiologists in detecting prostate cancer lesions. • However, this CAD system induces more false positives, particularly for less-experienced clinicians and in the transition zone. • CAD assists radiologists in detecting cancer missed on MRI, suggesting a path for improved diagnostic confidence. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the negative predictive value (NPV) of a negative prostate multi-parametric magnetic resonance imaging (mpMRI) in ruling out clinically significant prostate upon 12-core systematic biopsy. Methods: We retrospectively reviewed 114 men evaluated at our institution who underwent systematic 12-core biopsy within 1 year of a negative prostate mpMRI. Clinicopathologic features were evaluated and NPV was calculated for detection of clinically significant (Gleason ≥ 7) cancer. Regression analysis was performed to identify clinical predictors of biopsy outcome. Results: Overall, 88 (77.2%) patients in our cohort had no cancer detected upon biopsy. The highest pathologic grade was Gleason 6 (3 + 3) in 22 (19.3%) patients, and Gleason ≥ 7 in 4 (3.6%) patients. NPV for detecting Gleason ≥ 7 cancer was 96.5% (95% CI 93.1-99.9%) in the entire negative MRI cohort, 100% in those who were prostate biopsy naïve ( n = 20), 100% in those with a prior negative biopsy ( n = 53), and 90% in those who have had a previous positive biopsy and on active surveillance ( n = 41). Regression analysis identified no predictors of significant cancer in our cohort. Conclusion: In our cohort of men with no lesions detected on prostate mpMRI, we found very low rates of clinically significant cancer on systematic 12-core biopsy. In the few patients who diagnosed with prostate cancer, the majority had low-risk disease and could remain on active surveillance. Although validation studies and greater sample size is needed before clinical recommendations can be made, our data suggest patients with negative mpMRI evaluated by experienced radiologists may avoid unnecessary prostate biopsy and potential overtreatment. [ABSTRACT FROM AUTHOR]

Imaging of prostate cancer presents many challenges to the imaging community. There has been much progress in this space in large part due to MRI and PET radiopharmaceuticals. Though MRI has been focused on the evaluation of local disease and PETon the detection of metastatic disease, these two areas do converge and will be complementary especially with the growth of new PET/MRI technologies. In this review article, we review novel MRI, MRI/US, and PET radiopharmaceuticals which will offer insight into the future direction of imaging in prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: The posterior subcapsular region of the prostate is often undersampled by transrectal ultrasound (TRUS)-guided biopsy. The close proximity of these lesions to the posterior capsular wall of the prostate makes them difficult to localize while increasing the need for early detection because of their increased risk for extracapsular extension. We retrospectively evaluated the multiparametric MRI (mpMRI) features of subcapsular prostate cancers to make radiologists more aware of this condition.Materials and Methods: Between January 2010 and July 2014, all patients referred for 3T mpMRI and subsequent MR-US Fusion-guided biopsy (FgBx) and systematic 12-core sextant biopsy (SBx) under an IRB approved protocol, were reviewed, and imaging confirmed subcapsular prostate cancers were identified. Subcapsular lesions were defined as thin lesions that were just inside the prostate capsule. Matching patient demographics and clinical findings including age, PSA, PSA density, whole prostate volume, history of prostate cancer, Gleason score, and clinical management were tabulated.Results: Of 992 eligible patients, 33 patients had subcapsular lesions in the prostate detected by mpMRI. Mean age, PSA, and prostate volume in this group were 63 years (range: 52-76 years), 8.4 ng/mL (range: 1.22-65.20), and 53 mL (range: 12-125 mL), respectively. The combination biopsy (SBx + FgBx) confirmed prostate cancer in 24 of 33 patients (72.7%) and in 9 patients the biopsy was negative. Of the 24 cancers, 19 were confirmed on both FgBx and conventional biopsy; however, 5 cancers were only detected on FgBx. In 4 of the 19 patients in which both biopsy methods were positive, the FgBx yielded a higher Gleason score.Conclusion: Subcapsular lesions on mpMRI are relatively infrequent but are usually malignant. Although the majority are confirmed on conventional 12-core biopsies, about 20% of these lesions require FgBx for diagnosis, and FgBx more accurately grades the lesions in another 20%. Thus, FgBx is of considerable benefit in confirming the diagnosis of subcapsular prostate cancer despite their proximity to the prostatic capsule. [ABSTRACT FROM AUTHOR]

Approximately one in seven American men will be diagnosed with prostate cancer during his lifetime, and at least 50 % of newly diagnosed patients will present with low-risk disease. In the last decade, the decision-making paradigm for management has shifted due to high rates of disease detection and overtreatment, attributed to prostate-specific antigen screening, with more men deferring definitive treatment for active surveillance. The advent of multiparametric magnetic resonance imaging (MP-MRI) and MRI/ transrectal ultrasound-guided fusion-guided prostate biopsy has refined the process of diagnosis, identifying patients with clinicallysignificant cancer and larger disease burden who would most likely benefit from intervention. In parallel, the utilization of MP-MRI in the surveillance of low-grade, low-volume disease is on the rise, reflecting support in a growing body of literature. The aim of this review is to appraise and summarize the data evaluating the role of magnetic resonance imaging in active surveillance for prostate cancer. [ABSTRACT FROM AUTHOR]

Nodal staging is important in prostate cancer treatment. While surgical lymph node dissection is the classic method of determining whether lymph nodes harbor malignancy, this is a very invasive technique. Current noninvasive approaches to identifying malignant lymph nodes are limited. Conventional imaging methods rely on size and morphology of lymph nodes and have notoriously low sensitivity for detecting malignant nodes. New imaging techniques such as targeted positron emission tomography (PET) imaging and magnetic resonance lymphography (MRL) with iron oxide particles are promising for nodal staging of prostate cancer. In this review, the strengths and limitations of imaging techniques for lymph node staging of prostate cancer are discussed. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to investigate the utility of contrast-enhanced magnetic resonance imaging (CE-MRI), diffusion-weighted MRI (DW-MRI), and (68)Ga-DOTATOC positron emission tomography/computer tomography ((68)Ga-DOTATOC PET/CT) in the assessment of response to loco-regional peptide receptor radiotherapy (PRRT) with (90)Y-/(177)Lu-DOTATOC in patients with hepatic metastases from gastro-entero-pancreatic neuroendocrine tumors (GEP-NET).Procedures: CE-MRI, DW-MRI, and (68)Ga-DOTATOC-PET/CT images were acquired before and 3 months after one to two cycles of intra-arterial (90)Y-/(177)Lu-DOTATOC therapy in 14 patients (nine female, five male; mean age, 54 ± 9 years; range, 41-69 years) with hepatic metastases from GEP-NET. A total of 38 liver metastases were defined as target lesions for which the longest diameter, mean apparent diffusion coefficient (ADCmean) and maximum standardized uptake value (SUVmax) were assessed. Based on changes in size on follow-up imaging, target lesions were classified as responding (RL) or nonresponding (NRL). Relative changes in tumor size, ADCmean, and SUVmax were compared between the two subgroups.Results: A total of 27 responding and 11 nonresponding lesions were successfully evaluated. Mean ADCmean increased significantly in RL (p = 0.011) as well as NRL (p = 0.025). A significant correlation was found between baseline ADCmean and both the percent ADCmean change (p = 0.033) and decrease in lesion size after therapy (diameter p = 0.006; volume p = 0.002). SUVmax of RL declined significantly by 24.1 % (p = 0.014) and remained nearly unchanged in NRL. The change of SUVmax correlated significantly with the pretreatment SUVmax (p < 0.001) and the change in lesion diameter (p = 0.009). NRL with an ADCmean change >0.31 × 10(-3) mm(2)/s on first follow-up imaging showed a decrease in size in the long-term course.Conclusion: These results suggest that both DW-MRI and DOTATOC-PET imaging provide potential biomarkers for early assessment of treatment and stratification of therapy response, but that DW-MRI should be interpreted only in combination with SSTR expression and morphologic changes. [ABSTRACT FROM AUTHOR]

Three major modes of cancer therapy (surgery, radiation and chemotherapy) are the mainstay of modern oncologic therapy. To minimize the side effects of these therapies, molecular-targeted cancer therapies, including armed antibody therapy, have been developed with limited success. In this study, we have developed a new type of molecular-targeted cancer therapy, photoimmunotherapy (PIT), that uses a target-specific photosensitizer based on a near-infrared (NIR) phthalocyanine dye, IR700, conjugated to monoclonal antibodies (mAbs) targeting epidermal growth factor receptors. Cell death was induced immediately after irradiating mAb-IR700-bound target cells with NIR light. We observed in vivo tumor shrinkage after irradiation with NIR light in target cells expressing the epidermal growth factor receptor. The mAb-IR700 conjugates were most effective when bound to the cell membrane and produced no phototoxicity when not bound, suggesting a different mechanism for PIT as compared to conventional photodynamic therapies. Target-selective PIT enables treatment of cancer based on mAb binding to the cell membrane. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to develop and characterize the trafficking of a dual-modal agent that identifies primary draining or sentinel lymph node (LN).Procedure: Herein, a dual-reporting silica-coated iron oxide nanoparticle (SCION) is developed. Nude mice were imaged by magnetic resonance (MR) and optical imaging and axillary LNs were harvested for histological analysis. Trafficking through lymphatics was observed with intravital and ex vivo confocal microscopy of popliteal LNs in B6-albino, CD11c-EYFP, and lys-EGFP transgenic mice.Results: In vivo, SCION allows visualization of LNs. The particle's size and surface functionality play a role in its passive migration from the intradermal injection site and its minimal uptake by CD11c+ dendritic cells and CD169+ and lys+ macrophages.Conclusions: After injection, SCION passively migrates to LNs without macrophage uptake and then can be used to image LN(s) by MRI and fluorescence. Thus, SCION can potentially be developed for use in sentinel node resections or for intralymphatic drug delivery. [ABSTRACT FROM AUTHOR]

Purpose: Clinical translation of novel optical probes requires testing of human specimens ex vivo to ensure efficacy. However, it may be difficult to remove human tissue from the operating room due to regulatory/privacy issues. Therefore, we designed a portable fluorescence camera to test targeted optical imaging probes on human specimens in the operating room.Procedures: A compact benchtop fluorescence camera was designed and built in-house. A mouse xenograft model of ovarian cancer with an activatable imaging probe based on rhodamine green was used to test the device. Comparison was made to commercially available imaging systems.Results: The prototype camera produced images comparable to images acquired with commercially available, non-portable imaging systems.Conclusion: We demonstrate the feasibility of a specimen-based portable fluorescence camera for use in the operating room. Its small size ensures that tissue excised from patients can be tested promptly for fluorescence within the operating room environment, thus expediting the testing of novel imaging probes. [ABSTRACT FROM AUTHOR]

ARPKD/CHF is an inherited disease characterized by non-obstructive fusiform dilatation of the renal collecting ducts leading to enlarged spongiform kidneys and ductal plate malformation of the liver resulting in congenital hepatic fibrosis. ARPKD/CHF has a broad spectrum of clinical presentations involving the kidney and liver. Imaging plays an important role in the diagnosis and follow-up of ARPKD/CHF. Combined use of conventional and high-resolution US with MR cholangiography in ARPKD/CHF patients allows detailed definition of the extent of kidney and hepatobiliary manifestations without requiring ionizing radiation and contrast agents. [ABSTRACT FROM AUTHOR]

A long-term goal of cancer diagnosis is to develop tumor-imaging techniques that have sufficient specificity and sensitivity. To achieve this goal, minimizing the background signal originating from nontarget tissues is crucial. Here we achieve highly specific in vivo cancer visualization by using a newly designed targeted 'activatable' fluorescent imaging probe. This agent is activated after cellular internalization by sensing the pH change in the lysosome. Novel acidic pH–activatable probes based on the boron-dipyrromethene fluorophore were synthesized and then conjugated to a cancer-targeting monoclonal antibody. As proof of concept, ex vivo and in vivo imaging of human epidermal growth factor receptor type 2–positive lung cancer cells in mice was performed. The probe was highly specific for tumors with minimal background signal. Furthermore, because the acidic pH in lysosomes is maintained by the energy-consuming proton pump, only viable cancer cells were successfully visualized. The design concept can be widely adapted to cancer-specific, cell surface–targeting molecules that result in cellular internalization. [ABSTRACT FROM AUTHOR]

Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection, and virtually all cases of cervical cancer are attributable to infection by a subset of HPVs (reviewed in ref. 1). Despite the high incidence of HPV infection and the recent development of a prophylactic vaccine that confers protection against some HPV types, many features of HPV infection are poorly understood. It remains worthwhile to consider other interventions against genital HPVs, particularly those that target infections not prevented by the current vaccine. However, productive papillomavirus infection is species- and tissue-restricted, and traditional models use animal papillomaviruses that infect the skin or oral mucosa. Here we report the development of a mouse model of cervicovaginal infection with HPV16 that recapitulates the establishment phase of papillomavirus infection. Transduction of a reporter gene by an HPV16 pseudovirus was characterized by histology and quantified by whole-organ, multispectral imaging. Disruption of the integrity of the stratified or columnar genital epithelium was required for infection, which occurred after deposition of the virus on the basement membrane underlying basal keratinocytes. A widely used vaginal spermicide, nonoxynol-9 (N-9), greatly increased susceptibility to infection. In contrast, carrageenan, a polysaccharide present in some vaginal lubricants, prevented infection even in the presence of N-9, suggesting that carrageenan might serve as an effective topical HPV microbicide. [ABSTRACT FROM AUTHOR]

Advances in imaging are transforming our understanding of angiogenesis and the evaluation of drugs that stimulate or inhibit angiogenesis in preclinical models and human disease. Vascular imaging makes it possible to quantify the number and spacing of blood vessels, measure blood flow and vascular permeability, and analyze cellular and molecular abnormalities in blood vessel walls. Microscopic methods ranging from fluorescence, confocal and multiphoton microscopy to electron microscopic imaging are particularly useful for elucidating structural and functional abnormalities of angiogenic blood vessels. Magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), ultrasonography and optical imaging provide noninvasive, functionally relevant images of angiogenesis in animals and humans. An ongoing dilemma is, however, that microscopic methods provide their highest resolution on preserved tissue specimens, whereas clinical methods give images of living tissues deep within the body but at much lower resolution and specificity and generally cannot resolve vessels of the microcirculation. Future challenges include developing new imaging methods that can bridge this resolution gap and specifically identify angiogenic vessels. Another goal is to determine which microscopic techniques are the best benchmarks for interpreting clinical images. The importance of angiogenesis in cancer, chronic inflammatory diseases, age-related macular degeneration and reversal of ischemic heart and limb disease provides incentive for meeting these challenges. [ABSTRACT FROM AUTHOR]

Adrenal masses are a relatively common finding on computed tomography (CT) and magnetic resonance imaging (MRI). Until recently, adrenal biopsy, resection, or clinical follow-up were the only methods of distinguishing benign adenomas from malignancies. On the basis of their higher lipid content, adenomas have characteristic appearances on CT and MRI that can be used to separate them from non-lipid-containing lesions such as metastases. CT densitometry with or without contrast media and chemical shift MRI (CSI) are two examples of techniques with adequate sensitivity (50–90%) and excellent specificity (>95%) for adrenal adenomas. While the need for invasive tissue sampling is reduced because of these techniques, it is eliminated because lesions not meeting the criteria for adenomas are not always malignant. However, CT densitometry and CSI are likely to reduce significantly the need for histology sampling of incidentally discovered adrenal masses due to the high specificity of these new techniques. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review aims to highlight the limitations of current standard-of-care prostate cancer (PCa) imaging and discuss novel clinical imaging in advanced disease. Recent Findings: PCa staging through imaging is important for proper selections in clinical treatment. Traditional imaging techniques for metastatic disease (i.e., computed tomography [CT], magnetic resonance imaging [MRI], and radionuclide bone scan) have suboptimal performance in early recurrent or metastatic disease. Novel positron emission tomography agents including radiolabeled prostate specific membrane antigen (PSMA), choline, and anti-18F-fluorocyclobutane-1-carboxylic acid (18F-FACBC) have demonstrated improved sensitivity and specificity in initial staging and early biochemical recurrence (BCR). Summary: Conventional imaging modalities for PCa incompletely characterize disease burden. The development of new PET tracers in combination with CT and MRI offers superior anatomic localization and biologic correlation of tumor sites, which enhance providers' abilities to make appropriate decisions regarding treatment. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming is one of the defining features of cancer and abnormal metabolism is associated with many other pathologies. Molecular imaging techniques capable of detecting such changes have become essential for cancer diagnosis, treatment planning, and surveillance. In particular, 18F-FDG (fluorodeoxyglucose) PET has emerged as an essential imaging modality for cancer because of its unique ability to detect a disturbed molecular pathway through measurements of glucose uptake. However, FDG-PET has limitations that restrict its usefulness in certain situations and the information gained is limited to glucose uptake only.13C magnetic resonance spectroscopy theoretically has certain advantages over FDG-PET, but its inherent low sensitivity has restricted its use mostly to single voxel measurements unless dissolution dynamic nuclear polarization (dDNP) is used to increase the signal, which brings additional complications for clinical use. We show here a new method of imaging glucose metabolism in vivo by MRI chemical shift imaging (CSI) experiments that relies on a simple, but robust and efficient, post-processing procedure by the higher dimensional analog of singular value decomposition, tensor decomposition. Using this procedure, we achieve an order of magnitude increase in signal to noise in both dDNP and non-hyperpolarized non-localized experiments without sacrificing accuracy. In CSI experiments an approximately 30-fold increase was observed, enough that the glucose to lactate conversion indicative of the Warburg effect can be imaged without hyper-polarization with a time resolution of 12s and an overall spatial resolution that compares favorably to 18F-FDG PET. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is heterogeneous and expresses various cell surface targets. Photoimmunotherapy (PIT) involves monoclonal antibodies (MAbs) conjugated to a photoabsorber (PA), IR Dye 700Dx, and then activated by near infra-red light (NIR) to specifically target tumors. We have demonstrated that tumors expressing EGFR can be targeted with PIT. However, PIT may be less effective when a tumor lacks "overwhelming" expression of a single target such as EGFR. We present a combinatorial PIT approach for targeting BC expressing EGFR and HER2, using PA- labeled panitumumab (pan) and trastuzumab (tra), respectively. Human BC tissues and cell lines were analyzed for EGFR and HER2 expression. Efficacy of PA-labeled MAbs singly and in combination was analyzed. About 45% of BC tissues stain for both EGFR and HER2. In vitro, the combination of pan IR700 and tra IR700 with NIR was more efficacious than either agent alone. Tumor xenografts treated with combination PIT showed significant tumor growth retardation. Combination PIT is a promising approach for treating BC with low/moderate expression of surface receptors. In addition, given the molecular heterogeneity of bladder cancer, targeting more than one surface receptor may allow for more effective cell death across different bladder tumors. [ABSTRACT FROM AUTHOR]