Structural insights into the interactions of glutathione transferases with a nitric oxide carrier and sodium nitroprusside.

Glutathione transferases are detoxification enzymes with multifaceted roles, including a role in the metabolism and scavenging of nitric oxide (NO) compounds in cells. Here, we explored the ability of Trametes versicolor glutathione transferases (GSTs) from the Omega class (TvGSTOs) to bind metal-nitrosyl compounds. TvGSTOs have been studied previously for their ligandin role and are interesting models to study protein‒ligand interactions. First, we determined the X-ray structure of the TvGSTO3S isoform bound to the dinitrosyl glutathionyl iron complex (DNGIC), a physiological compound involved in the storage of nitric oxide. Our results suggested a different binding mode compared to the one previously described in human GST Pi 1 (GSTP1). Then, we investigated the manner in which TvGSTO3S binds three nonphysiological metal-nitrosyl compounds with different metal cores (iron, ruthenium and osmium). We assayed sodium nitroprusside, a well-studied vasodilator used in cases of hypertensive crises or heart failure. Our results showed that the tested GST can bind metal-nitrosyls at two distinct binding sites. Thermal shift analysis with six isoforms of TvGSTOs identified TvGSTO6S as the best interactant. Using the Griess method, TvGSTO6S was found to improve the release of nitric oxide from sodium nitroprusside in vitro, whereas the effects of human GST alpha 1 (GSTA1) and GSTP1 were moderate. Our results open new structural perspectives for understanding the interactions of glutathione transferases with metal-nitrosyl compounds associated with the biochemical mechanisms of NO uptake/release in biological systems.

Diffusion-Weighted MRI in the Genitourinary System.

Diffusion weighted imaging (DWI) constitutes a major functional parameter performed in Magnetic Resonance Imaging (MRI). The DW sequence is performed by acquiring a set of native images described by their b-values, each b-value representing the strength of the diffusion MR gradients specific to that sequence. By fitting the data with models describing the motion of water in tissue, an apparent diffusion coefficient (ADC) map is built and allows the assessment of water mobility inside the tissue. The high cellularity of tumors restricts the water diffusion and decreases the value of ADC within tumors, which makes them appear hypointense on ADC maps. The role of this sequence now largely exceeds its first clinical apparitions in neuroimaging, whereby the method helped diagnose the early phases of cerebral ischemic stroke. The applications extend to whole-body imaging for both neoplastic and non-neoplastic diseases. This review emphasizes the integration of DWI in the genitourinary system imaging by outlining the sequence's usage in female pelvis, prostate, bladder, penis, testis and kidney MRI. In gynecologic imaging, DWI is an essential sequence for the characterization of cervix tumors and endometrial carcinomas, as well as to differentiate between leiomyosarcoma and benign leiomyoma of the uterus. In ovarian epithelial neoplasms, DWI provides key information for the characterization of solid components in heterogeneous complex ovarian masses. In prostate imaging, DWI became an essential part of multi-parametric Magnetic Resonance Imaging (mpMRI) to detect prostate cancer. The Prostate Imaging-Reporting and Data System (PI-RADS) scoring the probability of significant prostate tumors has significantly contributed to this success. Its contribution has established mpMRI as a mandatory examination for the planning of prostate biopsies and radical prostatectomy. Following a similar approach, DWI was included in multiparametric protocols for the bladder and the testis. In renal imaging, DWI is not able to robustly differentiate between malignant and benign renal tumors but may be helpful to characterize tumor subtypes, including clear-cell and non-clear-cell renal carcinomas or low-fat angiomyolipomas. One of the most promising developments of renal DWI is the estimation of renal fibrosis in chronic kidney disease (CKD) patients. In conclusion, DWI constitutes a major advancement in genitourinary imaging with a central role in decision algorithms in the female pelvis and prostate cancer, now allowing promising applications in renal imaging or in the bladder and testicular mpMRI.

Sexual organ-sparing with hydrogel spacer injections for rectal cancer radiotherapy: a feasibility pilot study.

OBJECTIVES: The aim of this pilot study was to investigate in two rectal cancer patients undergoing neoadjuvant chemo-radiotherapy (nCRT) the implant feasibility and dosimetric benefit in sexual organ-sparing of an injectable, absorbable, radiopaque hydrogel spacer. METHODS: Two rectal cancer patients (one male and one female) underwent hydrogel implant between rectum and vagina/prostate before nCRT and curative surgery. A CT scan was performed before and after injection and a comparative dosimetric study was performed testing a standard (45/50 Gy) and a dose escalated (46/55.2 Gy) schedule. RESULTS: In both patients, the spacer implant in the recto-prostatic or recto-vaginal space was feasible and well tolerated. For the male, the dosimetric benefit with spacer was minimal for sexual organs. For the female however, doses delivered to the vagina were significantly reduced with spacer with a mean reduction of more than 5 Gy for both regimens. CONCLUSIONS: For organ preservation protocols and selected sexually active female patients, use of hydrogel spacers can be considered to spare sexual organs from the high radiotherapy dose levels. ADVANCES IN KNOWLEDGE: For females with advanced rectal tumor, a spacer implant between the rectum and the vagina before nCRT is feasible and reduces doses delivered to the vagina.

Diversity of Omega Glutathione Transferases in mushroom-forming fungi revealed by phylogenetic, transcriptomic, biochemical and structural approaches.

The Omega class of glutathione transferases (GSTs) forms a distinct class within the cytosolic GST superfamily because most of them possess a catalytic cysteine residue. The human GST Omega 1 isoform was first characterized twenty years ago, but it took years of work to clarify the roles of the human isoforms. Concerning the kingdom of fungi, little is known about the cellular functions of Omega glutathione transferases (GSTOs), although they are widely represented in some of these organisms. In this study, we re-assess the phylogeny and the classification of GSTOs based on 240 genomes of mushroom-forming fungi (Agaricomycetes). We observe that the number of GSTOs is not only extended in the order of Polyporales but also in other orders such as Boletales. Our analysis leads to a new classification in which the fungal GSTOs are divided into two Types A and B. The catalytic residue of Type-A is either cysteine or serine, while that of Type-B is cysteine. The present study focuses on Trametes versicolor GSTO isoforms that possess a catalytic cysteine residue. Transcriptomic data show that Type-A GSTOs are constitutive enzymes while Type-B are inducible ones. The crystallographic analysis reveals substantial structural differences between the two types while they have similar biochemical profiles in the tested conditions. Additionally, these enzymes have the ability to bind antioxidant molecules such as wood polyphenols in two possible binding sites as observed from X-ray structures. The multiplication of GSTOs could allow fungal organisms to adapt more easily to new environments.

Multi-seasonal modelling of plant-nematode interactions reveals efficient plant resistance deployment strategies.

Root-knot nematodes, Meloidogyne spp., are soil-borne polyphagous pests with major impact on crop yield worldwide. Resistant crops efficiently control avirulent root-knot nematodes, but favour the emergence of virulent forms. Since virulence is associated with fitness costs, susceptible crops counter-select virulent root-knot nematodes. In this study, we identify optimal rotation strategies between susceptible and resistant crops to control root-knot nematodes and maximize crop yield. We developed an epidemiological model describing the within-season dynamics of avirulent and virulent root-knot nematodes on susceptible or resistant plant root-systems, and their between-season survival. The model was fitted to experimental data and used to predict yield-maximizing rotation strategies, with special attention to the impact of epidemic severity and genetic parameters. Crop rotations were found to be efficient under realistic parameter ranges. They were characterized by low ratios of resistant plants and were robust to parameter uncertainty. Rotations provide significant gain over resistant-only strategies, especially under intermediate fitness costs and severe epidemic contexts. Switching from the current general deployment of resistant crops to custom rotation strategies could not only maintain or increase crop yield, but also preserve the few and valuable R-genes available.

Glutathione Transferases: Surrogate Targets for Discovering Biologically Active Compounds.

Glutathione transferases comprise a large class of multifunctional enzymes, some involved in detoxification pathways. Since these enzymes are able to interact with potentially toxic molecules, they could be used as targets to screen for compounds with biological activity. To test this hypothesis, glutathione transferases (GSTs) from the white-rot fungus Trametes versicolor have been used to screen for antifungal molecules from a library of tropical wood extracts. The interactions between a set of six GSTs from the omega class and 116 extracts from 21 tropical species were quantified using a high-throughput thermal shift assay. A correlation between these interactions and the antifungal properties of the tested extracts was demonstrated. This approach has been extended to the fractionation of an Andira coriacea extract and led to the detection of maackiain and lapachol in this wood. Altogether, the present results supported the hypothesis that such detoxification enzymes could be used to detect biologically active molecules.

A reverse chemical ecology approach to explore wood natural durability.

The natural durability of wood species, defined as their inherent resistance to wood-destroying agents, is a complex phenomenon depending on many biotic and abiotic factors. Besides the presence of recalcitrant polymers, the presence of compounds with antimicrobial properties is known to be important to explain wood durability. Based on the advancement in our understanding of fungal detoxification systems, a reverse chemical ecology approach was proposed to explore wood natural durability using fungal glutathione transferases. A set of six glutathione transferases from the white-rot Trametes versicolor were used as targets to test wood extracts from seventeen French Guiana neotropical species. Fluorescent thermal shift assays quantified interactions between fungal glutathione transferases and these extracts. From these data, a model combining this approach and wood density significantly predicts the wood natural durability of the species tested previously using long-term soil bed tests. Overall, our findings confirm that detoxification systems could be used to explore the chemical environment encountered by wood-decaying fungi and also wood natural durability.

Validation of the corticomedullary difference in magnetic resonance imaging-derived apparent diffusion coefficient for kidney fibrosis detection: a cross-sectional study.

BACKGROUND: Kidney cortical interstitial fibrosis (IF) is highly predictive of renal prognosis and is currently assessed by the evaluation of a biopsy. Diffusion magnetic resonance imaging (MRI) is a promising tool to evaluate kidney fibrosis via the apparent diffusion coefficient (ADC), but suffers from inter-individual variability. We recently applied a novel MRI protocol to allow calculation of the corticomedullary ADC difference (ΔADC). We here present the validation of ΔADC for fibrosis assessment in a cohort of 164 patients undergoing biopsy and compare it with estimated glomerular filtration rate (eGFR) and other plasmatic parameters for the detection of fibrosis. METHODS: This monocentric cross-sectional study included 164 patients undergoing renal biopsy at the Nephrology Department of the University Hospital of Geneva between October 2014 and May 2018. Patients underwent diffusion-weighted imaging, and T1 and T2 mappings, within 1 week after biopsy. MRI results were compared with gold standard histology for fibrosis assessment. RESULTS: Absolute cortical ADC or cortical T1 values correlated poorly to IF assessed by the biopsy, whereas ΔADC was highly correlated to IF (r=-0.52, P < 0.001) and eGFR (r = 0.37, P < 0.01), in both native and allograft patients. ΔT1 displayed a lower, but significant, correlation to IF and eGFR, whereas T2 did not correlate to IF nor to eGFR. ΔADC, ΔT1 and eGFR were independently associated with kidney fibrosis, and their combination allowed detection of extensive fibrosis with good specificity. CONCLUSION: ΔADC is better correlated to IF than absolute cortical or medullary ADC values. ΔADC, ΔT1 and eGFR are independently associated to IF and allow the identification of patients with extensive IF.

Bee pollination outperforms pesticides for oilseed crop production and profitability.

Nature-based agriculture that reduces dependency on chemical inputs requires using ecological principles for sustainable agro-ecosystems, aiming to balance ecology, economics and social justice. There is growing evidence that pollinator-dependent crops with high insect, particularly bee, pollination service can give higher yields. However, the interacting effects between insect pollination and agricultural inputs on crop yields and farm economics remain to be established to reconcile food production with biodiversity conservation. We quantified individual and combined effects of pesticides, insect pollination and soil quality on oilseed rape (Brassica napus L.) yield and gross margin, using a total of 294 farmers' fields surveyed between 2013 and 2016. We show that yield and gross margins are greater (15-40%) in fields with higher pollinator abundance than in fields with reduced pollinator abundance. This effect is, however, strongly reduced by pesticide use. Greater yields may be achieved by either increasing agrochemicals or increasing bee abundance, but crop economic returns were only increased by the latter, because pesticides did not increase yields while their costs reduced gross margins.

Recurrent prostate cancer after radical prostatectomy: restaging performance of 18F-choline hybrid PET/MRI.

To evaluate the diagnostic performance of a whole-body 18F-choline (FCH) hybrid PET/MRI for prostate cancer patients at biochemical relapse after radical prostatectomy (RP) compared to pelvic multiparametric MRI (mpMRI), one of the standard imaging modality for this patient population. From 2010 to 2016, 58 whole-body FCH PET/MRI studies with mpMRI acquisitions were performed in 53 prostate cancer patients relapsing after curative RP. Median PSA and PSA doubling time (PSA DT) at PET study were 1.5 ng/ml and 6.5 months, respectively. The overall positivity rate of FCH PET/MRI was 58.6% (n = 34), dropping to 44% in patients with a PSA ≤ 2 ng/ml (n = 36). Median PSA values in positive and negative PET/MRI studies were 2.2 ng/ml and 0.8 ng/ml, respectively, with no differences in PSA DT (6.5 vs. 6.6 months). A PSA value ≥ 1.5 ng/ml was a significant predictor of positivity on PET/MRI studies. Compared to PET, mpMRI identified more local relapses (17 vs. 14, p = 0.453) while PET outperformed whole-body Dixon MRI for regional (16 vs. 9, p = 0.016) and distant (12 vs. 6, p = 0.031) metastases. Compared to pelvic mpMRI, the treatment approach turned out to be influenced more frequently using whole-body FCH hybrid PET/MRI studies (58.6% vs. 38%). In prostate cancer patients with biochemical recurrence after RP, whole-body FCH PET/MRI achieved a higher detection rate of nodal/distant metastases compared to pelvic mpMRI alone, increasing the change of treatment strategy by more than 20%.

The structure of Trametes versicolor glutathione transferase Omega 3S bound to its conjugation product glutathionyl-phenethylthiocarbamate reveals plasticity of its active site.

Trametes versicolor glutathione transferase Omega 3S (TvGSTO3S) catalyzes the conjugation of isothiocyanates (ITC) with glutathione (GSH). Previously, this isoform was investigated in depth both biochemically and structurally. Structural analysis of complexes revealed the presence of a GSH binding site (G site) and a deep hydrophobic binding site (H site) able to bind plant polyphenols. In the present study, crystals of apo TvGSTO3S were soaked with glutathionyl-phenethylthiocarbamate, the product of the reaction between GSH and phenethyl isothiocyanate (PEITC). On the basis of this crystal structure, we show that the phenethyl moiety binds in a new site at loop ß2 -α2 while the glutathionyl part exhibits a particular conformation that occupies both the G site and the entrance to the H site. This binding mode is allowed by a conformational change of the loop ß2 -α2 at the enzyme active site. It forms a hydrophobic slit that stabilizes the phenethyl group at a distinct site from the previously described H site. Structural comparison of TvGSTO3S with drosophila DmGSTD2 suggests that this flexible loop could be the region that binds PEITC for both isoforms. These structural features are discussed in a catalytic context.

Trametes versicolor glutathione transferase Xi 3, a dual Cys-GST with catalytic specificities of both Xi and Omega classes.

Glutathione transferases (GSTs) from the Xi and Omega classes have a catalytic cysteine residue, which gives them reductase activities. Until now, they have been assigned distinct substrates. While Xi GSTs specifically reduce glutathionyl-(hydro)quinones, Omega GSTs are specialized in the reduction of glutathionyl-acetophenones. Here, we present the biochemical and structural analysis of TvGSTX1 and TvGSTX3 isoforms from the wood-degrading fungus Trametes versicolor. TvGSTX1 reduces GS-menadione as expected, while TvGSTX3 reduces both Xi and Omega substrates. An in-depth structural analysis indicates a broader active site for TvGSTX3 due to specific differences in the nature of the residues situated in the C-terminal helix α9. This feature could explain the catalytic duality of TvGSTX3. Based on phylogenetic analysis, we propose that this duality might exist in saprophytic fungi and ascomycetes.

Molecular recognition of wood polyphenols by phase II detoxification enzymes of the white rot Trametes versicolor.

Wood decay fungi have complex detoxification systems that enable them to cope with secondary metabolites produced by plants. Although the number of genes encoding for glutathione transferases is especially expanded in lignolytic fungi, little is known about their target molecules. In this study, by combining biochemical, enzymatic and structural approaches, interactions between polyphenols and six glutathione transferases from the white-rot fungus Trametes versicolor have been demonstrated. Two isoforms, named TvGSTO3S and TvGSTO6S have been deeply studied at the structural level. Each isoform shows two distinct ligand-binding sites, a narrow L-site at the dimer interface and a peculiar deep hydrophobic H-site. In TvGSTO3S, the latter appears optimized for aromatic ligand binding such as hydroxybenzophenones. Affinity crystallography revealed that this H-site retains the flavonoid dihydrowogonin from a partially purified wild-cherry extract. Besides, TvGSTO6S binds two molecules of the flavonoid naringenin in the L-site. These data suggest that TvGSTO isoforms could interact with plant polyphenols released during wood degradation.

The Effect of Neoadjuvant Androgen Deprivation Therapy on Tumor Hypoxia in High-Grade Prostate Cancer: An 18F-MISO PET-MRI Study.

PURPOSE: Tumor hypoxia is associated with radioresistance and poor prognosis after radiation therapy for prostate cancer (PCa). In this prospective pilot study, we assessed the ability of 18F-misonidazole (18F-MISO) positron emission tomography (PET)-magnetic resonance imaging (MRI) to detect hypoxia in high-grade PCa patients who were candidates for curative radiation therapy, and we evaluated 18F-MISO PET-MRI modulation after 3 months of neoadjuvant androgen deprivation therapy (nADT). METHODS AND MATERIALS: Eleven PCa patients with a Gleason score (GS) ≥ 8 underwent 18F-fluorocholine (18F-FCH) PET-computed tomography at diagnosis and an 18F-MISO hybrid PET-MRI examination before nADT; a second 18F-MISO PET-MRI examination was acquired after 3 months of nADT for all patients but one who dropped out because of noncompliance with nADT. Immunohistochemistry for tissue hypoxia- and proliferation-related biomarkers (glucose transporter 1, carbonic anhydrase IX, vascular endothelial growth factor A, Ki-67, hypoxia-inducible factor 1 alpha, and epidermal growth factor receptor) was performed in lesions bearing the highest GS. We used nonparametric tests to assess (1) the presence of 18F-MISO-positive regions (tumor-to-background ratio [TBR] ≥ 1.4) at baseline; (2) the correlation between imaging parameters (PET tracer uptake, Prostate Imaging Reporting and Data System [PIRADS] scores, and dynamic contrast enhancement perfusion markers) at baseline; (3) the difference in immunohistochemistry staining between 18F-MISO-positive and -negative lesions; and (4) the changes in 18F-MISO PET-MRI after nADT. RESULTS: Uptake of 18F-MISO was significant in 7 patients, being coincidental with the highest GS region in 5 of them. A significant correlation was found at baseline between GS and 18F-MISO TBR, between 18F-MISO TBR and MRI perfusion markers, between GS and 18F-FCH maximum standardized uptake value, between GS and PIRADS score, and between 18F-FCH maximum standardized uptake value and PIRADS score. No difference was found between 18F-MISO-positive and -negative biopsy specimens with respect to tissue biomarkers. The TBR of 18F-MISO diminished significantly after nADT only in high-grade lesions and in regions with a significant uptake at baseline. CONCLUSIONS: PET imaging with 18F-MISO showed variable uptake in PCa, associated with a higher GS, lowering significantly after 3 months of nADT in high-grade lesions. These results suggest the existence of a hypoxic microenvironment in PCa and a reoxygenation effect of nADT.

Structural plasticity among glutathione transferase Phi members: natural combination of catalytic residues confers dual biochemical activities.

The glutathione transferase (GST) gene family is divided into 14 classes in photosynthetic organisms. Among them, the Phi class (GSTF) is composed of a large number of genes that are often induced in response to environmental constraints due to their ability to detoxify xenobiotics, to their peroxidase activity and to their involvement in the biosynthesis and/or transport of secondary metabolites. However, the exact functions of GSTFs from many plants including Populus trichocarpa are unknown. Here, following GSTF1 characterization, we have performed a comparative analysis of the seven other GSTFs found in poplar by systematically evaluating the biochemical and enzymatic properties of the corresponding recombinant proteins and of variants mutated for active site residues and by determining the three-dimensional structures of several representatives. Owing to the presence of a cysteine with a pKa value around 5 in their active site, GSTF3, F7, and F8 displayed a thiol transferase activity in addition to the usual glutathione transferase and peroxidase activities. From structural analyses, it appeared that these dual biochemical properties originate from the existence of a certain variability in the ß1-α1 loop. This allows positioning of several active site residues at proximity of the glutathione molecule, which itself remains unchanged in GSTF three-dimensional structures. These results highlight the promiscuity of some GSTFs and that changes of active site residues in some isoforms during evolution generated functional diversity by modifying their activity profile. DATABASE: Structural data are available in the PDB under the accession numbers 5EY6, 5F05, 5F06, and 5F07.

Comparison of readout-segmented and conventional single-shot for echo-planar diffusion-weighted imaging in the assessment of kidney interstitial fibrosis.

PURPOSE: To compare readout-segmented echo-planar imaging (EPI) (RESOLVE) to single-shot EPI (ss-EPI) diffusion-weighted imaging (DWI) for the assessment of renal interstitial fibrosis. MATERIALS AND METHODS: A phantom, eight healthy volunteers (under 30 years to avoid age-fibrosis related) and 27 chronic kidney disease (CKD) patients (scheduled for kidney biopsy) were scanned (at 3T) with ss-EPI and 5-shot RESOLVE DWI (resolution: 2 × 2 × 5 mm3 , 10 b-values). The cortico-medullary difference for each DW parameter from a monoexponential fit (ΔADC) or, segmented biexponential fit (ΔD, ΔD*, ΔFp ) were compared between both sequences. A fibrosis threshold of 40% was defined to separate all 35 subjects into low and high fibrosis groups. The linear relationship between DW parameters and percentage fibrosis (up to 80%) from Masson trichrome was assessed with the Pearson product-moment correlation coefficient. Fisher Z-transform was used for R2 correlation comparison. RESULTS: A coefficient of variation between ADCs of 3% was measured between both sequences in the phantom. In healthy volunteers, no significant difference was measured for all DW parameters. Both sequences separated low to high level of fibrosis with a significant decrease of ΔADC (RESOLVE P = 3.1 × 10-6 , ss-EPI P = 0.003) and ΔD (RESOLVE P = 8.2 × 10-5 , ss-EPI P = 0.02) in the high level of fibrosis. However, RESOLVE ΔADC had a stronger negative correlation (P = 0.04 for R2 comparison) with fibrosis than ss-EPI ΔADC (RESOLVE R2 = 0.65, P = 5.9 × 10-9 , ss-EPI R2 = 0.29, P = 8.9 × 10-4 ). ΔD (RESOLVE) was correlated (moderately) with fibrosis (R2 = 0.29, P = 9.2 × 10-4 ); however, ΔD* and ΔFp did not show, in our population, a significant correlation with interstitial fibrosis (0.01 < R2 < 0.08). CONCLUSION: ΔADC derived from both sequences correlated with fibrosis. ΔADC from RESOLVE showed better correlation with fibrosis than ΔADC from ss-EPI and therefore has potential to monitor CKD. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1631-1640.

Prostatic Utricle Cyst as the Most Likely Cause in a Case of Recurrent Episodes of Hematospermia.

Hematospermia is a clinical symptom that raises anxiety in patients and has various causes, benign and malignant. We report a case of hematospermia for which appropriate multidisciplinary expertise favored a conservative management of a benign prostatic cyst, namely, a prostatic utricle cyst. A cystic lesion found by transrectal ultrasound in the context of hematospermia related to masturbation in a young virgin male patient was investigated with a high-field magnetic resonance imaging (MRI) and an endorectal coil. The association of high-field MRI and endorectal coil leads to high quality images.

Transrectal Ultrasound-Guided Prostate Biopsy for Cancer Detection: Performance of 2D-, 3D- and 3D-MRI Fusion Targeted Techniques.

INTRODUCTION: The study aimed to evaluate 3 different modalities of transrectal ultrasound (TRUS)-guided prostate biopsies (PBs; 2D-, 3D- and targeted 3D-TRUS with fusion to MRI - T3D). Primary end point was the detection rate of prostate cancer (PC). Secondary end point was the detection rate of insignificant PC according to the Epstein criteria. PATIENTS AND METHODS: Inclusion of 284 subsequent patients who underwent 2D-, 3D- or T3D PB from 2011 to 2015. All patients having PB for initial PC detection with a serum prostate-specific antigen value ≤20 ng/ml were included. Patients with T4 and/or clinical and/or radiological metastatic disease, so as these under active surveillance were excluded. RESULTS: Patients with T3D PB had a significantly higher detection rate of PC (58 vs. 19% for 2D and 38% for 3D biopsies; p = 0.001), with no difference in Gleason score distribution (p = 0.644), as well as detection rate of low-risk cancers (p = 0.914). Main predictive factor for positive biopsies was the technique used, with respectively a 3- and 8-fold higher detection rate in the 3D- and T3D group. For T3D-PB, there was a significant correlation between radiological cancer suspicion (Prostate Imaging Reporting and Data System Score) and cancer detection rate (p = 0.02). CONCLUSIONS: T3D PB should be preferred over 2D PB and 3D PB in patients with suspected PC as it improves the cancer detection rate.

Target Definition in Salvage Radiotherapy for Recurrent Prostate Cancer: The Role of Advanced Molecular Imaging.

Salvage radiotherapy (SRT) represents the main treatment option for relapsing prostate cancer in patients after radical prostatectomy. Several open questions remain unanswered in terms of target volumes definition and delivered doses for SRT: the effective dose necessary to achieve biochemical control in the SRT setting may be different if the tumor recurrence is micro- or macroscopic. At the same time, irradiation of only the prostatic bed or of the whole pelvis will depend on the localization of the recurrence, local or locoregional. In the "theragnostic imaging" era, molecular imaging using positron emission tomography (PET) constitutes a useful tool for clinicians to define the site of the recurrence, the extent of disease, and individualize salvage treatments. The best option currently available in clinical routine is the combination of radiolabeled choline PET imaging and multiparametric magnetic resonance imaging (MRI), associating the nodal and distant metastases identification based on PET with the local assessment by MRI. A new generation of targeted tracers, namely, prostate-specific membrane antigen, show promising results, with a contrast superior to choline imaging and a higher detection rate even for low prostate-specific antigen levels; validation studies are ongoing. Finally, imaging targeting bone remodeling, using whole-body SPECT-CT, is a relevant complement to molecular/metabolic PET imaging when bone involvement is suspected.

Diffusion in prostate cancer detection on a 3T scanner: How many b-values are needed?

PURPOSE: To assess the influence of perfusion on apparent coefficient diffusion (ADC) maps, the contribution of b-value images, and the number of b-values needed in prostate cancer detection by diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Patients scheduled for prostatectomy were scanned by 3T magnetic resonance imaging (MRI) with DWI based on b-values 0-500-1000-1500 s/mm(2) . A monoexponential model was fitted to obtain ADC using multiple b-values, with or without b0 (perfusion-sensitive ADC4b-b0-500-1000-1500 , perfusion-insensitive ADC3b-b500-1000-1500 ), or two b-values (ADC2b-b0-500 , ADC2b-b0-1000 , ADC2b-b0-1500 ). Prostate and cancer foci were segmented to label voxels as normal or tumoral, according to histology. Areas under receiver operating characteristic curves (AUC) were calculated for each ADC and b-value, then for multivariate logistic regression models combining them. A threshold of 85 tumoral voxels (=0.5 cm(3) ) was used to stratify AUC analysis. RESULTS: In all, 21 patients were selected. Segmentation collected 143,665 prostatic voxels including 10,069 tumoral voxels. In five patients, tumor segmentation provided fewer than 85 voxels, resulting in an ADC with AUC inferior to 0.52. In 16 patients with larger tumors, perfusion-sensitive ADC4b-b0-500-1000-1500 performed better than perfusion-insensitive ADC3b-b500-1000-1500 and similar to ADC2b-b0-1500 (AUC of 0.840, 0.809, and 0.838, respectively). In comparison to the ADC alone, models combining ADC4b-b0-500-1000-1500 or ADC2b-b0-1500 with b1500 improved performance, leading to similar AUCs of 0.884 and 0.883, respectively. In both models, ADC and b1500 were significant markers (P < 0.001). CONCLUSION: Including b0 in ADC calculation provided superior ADC maps for prostate cancer detection. b1500 images as a combined parameter with ADC also improved performance. Using more than two b-values showed no improvement. J. Magn. Reson. Imaging 2016;44:601-609.