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Immune cells such as macrophages are drivers and biomarkers of most cancers. Scoring macrophage infiltration in tumor tissue provides a prognostic assessment that is correlated with disease outcome and therapeutic response, but generally requires invasive biopsy. Routine detection of hemosiderin iron aggregates in macrophages in other settings histologically and in vivo by MRI suggests that similar assessments in cancer can bridge a gap in our ability to assess tumor macrophage infiltration. Quantitative histological and in vivo MRI assessments of non-heme cellular iron revealed that preclinical prostate tumor models could be differentiated according to hemosiderin iron accumulation-both in tumors and systemically. Monitoring cellular iron levels during "off-label" administration of the FDA-approved iron chelator deferiprone evidenced significant reductions in tumor size without extensive perturbation to these iron deposits. Spatial profiling of the iron-laden infiltrates further demonstrated that higher numbers of infiltrating macrophage iron deposits was associated with lower anti-tumor chelation therapy response. Imaging macrophages according to their innate iron status provides a new phenotypic window into the immune tumor landscape and reveals a prognostic biomarker associated with macrophage infiltration and therapeutic outcome.

Cancer growth and proliferation rely on intracellular iron availability. We studied the effects of Deferiprone (DFP), a chelator of intracellular iron, on three prostate cancer cell lines: murine, metastatic TRAMP-C2; murine, non-metastatic Myc-CaP; and human, non-metastatic 22rv1. The effects of DFP were evaluated at different cellular levels: cell culture proliferation and migration; metabolism of live cells (time-course multi-nuclear magnetic resonance spectroscopy cell perfusion studies, with 1- 13 C-glucose, and extracellular flux analysis); and expression (Western blot) and activity of mitochondrial aconitase, an iron-dependent enzyme. The 50% and 90% inhibitory concentrations (IC 50 and IC 90 , respectively) of DFP for the three cell lines after 48 h of incubation were within the ranges 51-67 μM and 81-186 μM, respectively. Exposure to 100 μM DFP led to: (i) significant inhibition of cell migration after different exposure times, ranging from 12 h (TRAMP-C2) to 48 h (22rv1), in agreement with the respective cell doubling times; (ii) significantly decreased glucose consumption and glucose-driven tricarboxylic acid cycle activity in metastatic TRAMP-C2 cells, during the first 10 h of exposure, and impaired cellular bioenergetics and membrane phospholipid turnover after 23 h of exposure, consistent with a cytostatic effect of DFP. At this time point, all cell lines studied showed: (iii) significant decreases in mitochondrial functional parameters associated with the oxygen consumption rate, and (iv) significantly lower mitochondrial aconitase expression and activity. Our results indicate the potential of DFP to inhibit prostate cancer proliferation at clinically relevant doses and plasma concentrations., (Copyright © 2017 John Wiley & Sons, Ltd.)

Purpose: To assess whether an artificial neural network (ANN) model is a useful tool for automatic detection of cancerous voxels in the prostate from (1)H-MRSI datasets and whether the addition of information about anatomical segmentation improves the detection of cancer., Materials and Methods: The Institutional Review Board approved this HIPAA-compliant study and waived informed consent. Eighteen men with prostate cancer (median age, 55 years; range, 36-71 years) who underwent endorectal MRI/MRSI before radical prostatectomy were included in this study. These patients had at least one cancer area on whole-mount histopathological map and at least one matching MRSI voxel suspicious for cancer detected. Two ANN models for automatic classification of MRSI voxels in the prostate were implemented and compared: model 1, which used only spectra as input, and model 2, which used the spectra plus information from anatomical segmentation. The models were trained, tested and validated using spectra from voxels that the spectroscopist had designated as cancer and that were verified on histopathological maps., Results: At ROC analysis, model 2 (AUC = 0.968) provided significantly better (P = 0.03) classification of cancerous voxels than did model 1 (AUC = 0.949)., Conclusion: Automatic analysis of prostate MRSI to detect cancer using ANN model is feasible. Application of anatomical segmentation from MRI as an additional input to ANN improves the accuracy of detecting cancerous voxels from MRSI., (© 2013 Wiley Periodicals, Inc.)

Generally, solid tumors (>400 mm(3)) are inherently acidic, with more aggressive growth producing greater acidity. If the acidity could be targeted as a biomarker, it would provide a means to gauge the pace of tumor growth and degree of invasiveness, as well as providing a basis for predicting responses to pH-dependent chemotherapies. We have developed a (64)Cu pH (low) insertion peptide (pHLIP) for targeting, imaging, and quantifying acidic tumors by PET, and our findings reveal utility in assessing prostate tumors. The new pHLIP version limits indiscriminate healthy tissue binding, and we demonstrate its targeting of extracellular acidification in three different prostate cancer models, each with different vascularization and acid-extruding protein carbonic anhydrase IX (CAIX) expression. We then describe the tumor distribution of this radiotracer ex vivo, in association with blood perfusion and known biomarkers of acidity, such as hypoxia, lactate dehydrogenase A, and CAIX. We find that the probe reveals metabolic variations between and within tumors, and discriminates between necrotic and living tumor areas.

Combinatorial activation of PI3-kinase and RAS signaling occurs frequently in advanced prostate cancer and is associated with adverse patient outcome. We now report that the oncogenic Ets variant 4 (Etv4) promotes prostate cancer metastasis in response to coactivation of PI3-kinase and Ras signaling pathways in a genetically engineered mouse model of highly penetrant, metastatic prostate cancer. Using an inducible Cre driver to simultaneously inactivate Pten while activating oncogenic Kras and a fluorescent reporter allele in the prostate epithelium, we performed lineage tracing in vivo to define the temporal and spatial occurrence of prostate tumors, disseminated tumor cells, and metastases. These analyses revealed that though disseminated tumors cells arise early following the initial occurrence of prostate tumors, there is a significant temporal lag in metastasis, which is temporally coincident with the up-regulation of Etv4 expression in primary tumors. Functional studies showed that knockdown of Etv4 in a metastatic cell line derived from the mouse model abrogates the metastatic phenotype but does not affect tumor growth. Notably, expression and activation of ETV4, but not other oncogenic ETS genes, is correlated with activation of both PI3-kinase and Ras signaling in human prostate tumors and metastases. Our findings indicate that ETV4 promotes metastasis in prostate tumors that have activation of PI3-kinase and Ras signaling, and therefore, ETV4 represents a potential target of therapeutic intervention for metastatic prostate cancer.

The spectral changes of native fluorophores among normal fibroblasts and cancer cell lines of different metastatic ability are investigated by fluorescence spectroscopy. The normal (fibroblast), moderately metastatic (DU-145), and advanced metastatic (PC-3) cell lines were each selectively excited at 300 nm, and their fluorescence emission spectra are analyzed using principal component analysis to explore the differences of the relative contents of tryptophan and reduced nicotinamide adenine dinucleotide in these cell lines. The results show that the tryptophan emission featured predominantly in the fluorescence spectra of the advanced metastatic cancer cells in comparison with the moderately metastatic cancer and normal cells.

Tumor hypoxia develops heterogeneously, affects radiation sensitivity and the development of metastases. Prognostic information derived from the in vivo characterization of the spatial distribution of hypoxic areas in solid tumors can be of value for radiation therapy planning and for monitoring the early treatment response. Tumor hypoxia is caused by an imbalance between the supply and consumption of oxygen. The tumor oxygen supply is inherently linked to its vasculature and perfusion which can be evaluated by dynamic contrast enhanced (DCE-) MRI using the contrast agent Gd-DTPA. Thus, we hypothesize that DCE-MRI data may provide surrogate information regarding tumor hypoxia. In this study, DCE-MRI data from a rat prostate tumor model were analysed with a Gaussian mixture model (GMM)-based classification to identify perfused, hypoxic and necrotic areas for a total of ten tumor slices from six rats, of which one slice was used as training data for GMM classifications. The results of pattern recognition analyzes were validated by comparison to corresponding Akep maps defining the perfused area (0.84 ± 0.09 overlap), hematoxylin and eosin (H&E)-stained tissue sections defining necrosis (0.64 ± 0.15 overlap) and pimonidazole-stained sections defining hypoxia (0.72 ± 0.17 overlap), respectively. Our preliminary data indicate the feasibility of a GMM-based classification to identify tumor hypoxia, necrosis and perfusion/permeability from non-invasively acquired, in vivo DCE-MRI data alone, possibly obviating the need for invasive procedures, such as biopsies, or exposure to radioactivity, such as positron emission tomography (PET) exams., (Copyright © 2013 John Wiley & Sons, Ltd.)

The contextual signals that regulate the expansion of prostate tumor progenitor cells are poorly defined. We found that a significant fraction of advanced human prostate cancers and castration-resistant metastases express high levels of the β4 integrin, which binds to laminin-5. Targeted deletion of the signaling domain of β4 inhibited prostate tumor growth and progression in response to loss of p53 and Rb function in a mouse model of prostate cancer (PB-TAg mice). Additionally, it suppressed Pten loss-driven prostate tumorigenesis in tissue recombination experiments. We traced this defect back to an inability of signaling-defective β4 to sustain self-renewal of putative cancer stem cells in vitro and proliferation of transit-amplifying cells in vivo. Mechanistic studies indicated that mutant β4 fails to promote transactivation of ErbB2 and c-Met in prostate tumor progenitor cells and human cancer cell lines. Pharmacological inhibition of ErbB2 and c-Met reduced the ability of prostate tumor progenitor cells to undergo self-renewal in vitro. Finally, we found that β4 is often coexpressed with c-Met and ErbB2 in human prostate cancers and that combined pharmacological inhibition of these receptor tyrosine kinases exerts antitumor activity in a mouse xenograft model. These findings indicate that the β4 integrin promotes prostate tumorigenesis by amplifying ErbB2 and c-Met signaling in tumor progenitor cells.

Longitudinal studies of lactate MRSI and dynamic contrast-enhanced MRI were performed at 4.7 T in two prostate tumor models grown in rats, Dunning R3327-AT (AT) and Dunning R3327-H (H), to determine the potential of lactate and the perfusion/permeability parameter Ak(ep) as markers of tumor aggressiveness. Subcutaneous AT (n = 12) and H (n = 6) tumors were studied at different volumes between 100 and 2900 mm(3) (Groups 1-5). Lactate concentration was determined using selective multiple quantum coherence MRSI with the phantom substitution method. Tumor enhancement after the administration of gadolinium diethylenetriaminepenta-acetic acid was analyzed using the Brix-Hoffmann model and the Ak(ep) parameter was used as a measure of tumor perfusion/permeability. Lactate was not detected in the smallest AT tumors (Group 1; 100-270 mm(3) ). In larger AT tumors, the lactate concentration increased from 2.8 ± 1.0 mm (Group 2; 290-700 mm(3)) to 8.4 ± 2.9 mm (Group 3; 1000-1340 mm(3)) and 8.2 ± 2.2 mm (Group 4; 1380-1750 mm(3) ), and then decreased to 5.0 ± 1.7 mm (Group 5; 1900-2500 mm(3)), and was consistently higher in the tumor core than in the rim. Lactate was not detected in any of the H tumors. The mean tumor Ak(ep) values decreased with increasing volume in both tumor types, but were significantly higher in H tumors. In AT tumors, the Ak(ep) values were significantly higher in the rim than in the core. Histological hypoxic and necrotic fractions in AT tumors increased with volume from 0% in Group 1 to about 20% and 30%, respectively, in Group 5. Minimal amounts of hypoxia and necrosis were found in H tumors of all sizes. Thus, the presence of lactate and heterogeneous perfusion/permeability are signatures of aggressive, metabolically deprived tumors., (Copyright © 2011 John Wiley & Sons, Ltd.)

Purpose: Radical prostatectomy has significant side effects. Preoperative information predicting its long-term outcome would be valuable to patients and physicians. We determined whether pretreatment endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging predicts biochemical recurrence after radical prostatectomy., Materials and Methods: Of 202 patients who underwent endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging from January 2000 to December 2002 before radical prostatectomy 130 satisfied study inclusion criteria and were included in analysis. We compared imaging factors with potential predictive capability to biochemical recurrence data, including magnetic resonance imaging risk score based on local disease extent and magnetic resonance spectroscopic imaging index lesion characteristics, such as the number of voxels and degree of metabolic abnormality (magnetic resonance spectroscopic imaging grade). We evaluated associations of these imaging variables with time to biochemical recurrence by Cox proportional hazards regression adjusted for known predictors of biochemical recurrence, such as stage, grade and prostate specific antigen., Results: At a median 68-month followup there were 26 biochemical failures. Risk score, lesion volume and high grade voxels each correlated with time to biochemical recurrence. In a model combining clinical parameters risk score, lesion volume and at least 1 high grade voxel the magnetic resonance spectroscopic imaging variables remained significant but the magnetic resonance imaging score dropped out., Conclusions: Index lesion volume on magnetic resonance spectroscopic imaging and high grade magnetic resonance spectroscopic imaging voxels correlate with time to biochemical recurrence after radical prostatectomy even when adjusted for clinical data. Results suggest the preoperative predictive usefulness of endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging in patients considering radical prostatectomy., (Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

17-Allylamino, 17-demethoxygeldanamycin (17-AAG), an effective inhibitor of the heat shock protein hsp90, preferentially inhibiting tumor hsp90 compared to hsp90 from normal cells, has shown promising results against several cancers, including hormone-resistant prostate cancer. Levels of several oncogenic proteins critical to tumor growth and progression, such as androgen receptor and HER2/neu, were reduced 4 h post 17-allylamino, 17-demethoxygeldanamycin treatment. Posttreatment metabolic changes have also been observed in several tumor cell lines. In this study, total choline distributions in hormone sensitive CWR22 and hormone resistant CWR22r prostate cancer xenograft tumors in mice were measured before and at 4 h and 48 h after a single-bolus 17-allylamino, 17-demethoxygeldanamycin treatment at 100 mg/kg, using proton MR spectroscopy. Our results show that tumor total choline levels declined 4 h after the treatment for CWR22 (P = 0.001) and 48 h post treatment for CWR22r (P = 0.003). Metabolic changes, in particular of total choline intensity detected by proton magnetic resonance spectroscopic imaging (MRSI), are consistent with the observed immunohistochemistry changes, tumor growth inhibition for CWR22r (P = 0.01 at 14 days post treatment), and a constant prostate specific antigen level versus increasing prostate specific antigen for control CWR22 (P = 0.01). Metabolic changes in total choline by proton MRSI can be used as an early biomarker of response for advanced-stage prostate cancer in targeted therapy such as 17-allylamino, 17-demethoxygeldanamycin., ((c) 2009 Wiley-Liss, Inc.)

Purpose: To test the hypothesis that, with 5-fluorocytosine (5-FC) treatment, the co-expression of cytosine deaminase (CD) and uracil phosphoribosyltransferase (UPRT) can lead to greater radiosensitization and bystander effect than CD-expression alone., Methods and Materials: R3327-AT cell lines stably expressing CD or CDUPRT were generated. The 5-FC and 5-FU cytotoxicity, and the radiosensitivity with/without 5-FC treatment, of these cells were evaluated under both aerobic and hypoxic conditions. The bystander effect was assessed by apoptosis staining and clonogenic survival. The pharmacokinetics of 5-FU and 5-FC metabolism was monitored in mice bearing CD- or CDUPRT-expressing tumors using 19F MR spectroscopy (MRS)., Results: CDUPRT-expressing cells were more sensitive to 5-FC and 5-FU than CD-expressing cells. CDUPRT-expression further enhanced the radiosensitizing effect of 5-FC, relative to that achieved by CD-expression alone. A 25-fold lower dose of 5-FC resulted in the same magnitude of radiosensitization in CDUPRT-expressing cells, relative to that in CD-expressing cells. The 5-FC cytotoxicity in co-cultures of parental cells mixed with 10-20% CDUPRT cells was similar to that in 100% CDUPRT cells. 19F MRS measurements showed that expression of CDUPRT leads to enhanced accumulation of fluorine nucleotide (FNuc), relative to that associated with CD-expression alone., Conclusion: Our study suggests that CDUPRT/5-FC strategy may be more effective than CD/5-FC, especially when used in combination with radiation.

Tumor vasculature and tissue oxygen pressure can influence tumor growth, metastases, and patient survival. Elevated levels of lactate may be observed during the process of aggressive tumor development accompanied by angiogenesis (the evolution of the microenvironment). The noninvasive MR detection of lactate in tumor tissues as a potential biomarker is difficult due to the presence of co-resonating lipids that are present at high concentrations. Methods were previously reported for lactate editing using the SELective Multiple Quantum Coherence (SelMQC) method. Here we report a sequence "SS-SelMQC," Spectral-Selective SelMQC, which is a modified version of SelMQC using binomial pulses. Binomial pulses were employed in this editing sequence for frequency excitation or inversion of selective lactate resonances. Lactate detection has been demonstrated using SS-SelMQC, both in vitro (30 mM lactate/H(2)O doped with 25 microM Gd-DTPA) and in vivo (Dunning R3337-AT prostate tumors), and compared to similar measurements made with SelMQC. Lactate areas were measured from nonlocalized spectra, one-dimensional (1D) localized spectra, and two-dimensional chemical shift images (CSI) of the localized slice. In data from whole phantoms, the modified pulse sequence yielded enhancement of the lactate signal of 2.4 +/- 0.40 times compared to SelMQC. Similar in vivo lactate signal enhancement of 2.3 +/- 0.24 times was observed in 1D slice-localized experiment.

One reported function of the tumor suppressor p19(Arf) is to stabilize p53, providing a critical checkpoint in the response to oncogenic insults. Acute loss of Pten leads to an increase in the abundance of p19(Arf), p53, and p21 proteins as part of a fail-safe senescence response. Here, we report that loss of p19(Arf) in prostate epithelium does not accelerate-but rather partially inhibits-the prostate cancer phenotype of Pten-deficient mice. Moreover, cellular senescence and a further decrease in the number of pre-neoplastic glands were observed in prostates of the Pten-p19(Arf) double-mutant mice. In both prostate epithelium and primary mouse embryo fibroblasts (MEFs), the increase in p53 protein abundance found upon loss of Pten was unaffected by the simultaneous loss of p19(Arf). However, in contrast to that in the prostate epithelium, p19(Arf) deficiency in MEFs lacking Pten abolished cell senescence and promoted hyperproliferation and transformation despite the unabated increase in p53 abundance. Consistent with the effect of p19(Arf) loss in Pten-deficient mouse prostate, we found that in human prostate cancers, loss of PTEN was not associated with loss of p14(ARF) (the human equivalent of mouse p19(Arf)). Collectively, these data reveal differential consequences of p19(Arf) inactivation in prostate cancer and MEFs upon Pten loss that are independent of the p53 pathway.

Purpose: To retrospectively determine the accuracy of diffusion-weighted (DW) magnetic resonance (MR) imaging for identifying cancer in the prostate peripheral zone (PZ) and to assess the accuracy of tumor volume measurements made with T2-weighted imaging and combined T2-weighted and DW MR imaging by using surgical pathologic examination as the reference standard., Materials and Methods: The institutional review board issued a waiver of informed consent for this HIPAA-compliant study. Forty-two patients underwent endorectal MR at 1.5 T before undergoing radical prostatectomy for prostate cancer and had at least one PZ tumor larger than 0.1 cm(3) at surgical pathologic examination. On T2-weighted images, an experienced radiologist outlined suspected PZ tumors. Two apparent diffusion coefficient (ADC) cutoff values were identified by using the Youden index and published literature. Image cluster analysis was performed on voxels within the suspected tumor regions. Associations between volume measurements from imaging and from pathologic examination were assessed by using concordance correlation coefficients (CCCs). The sensitivity and specificity of ADCs for identifying malignant PZ voxels were calculated., Results: In identifying malignant voxels, respective ADC cutoff values of 0.0014 and 0.0016 mm(2)/sec yielded sensitivity of 82% and 95% and specificity of 85% and 65%, respectively. Sixty PZ cancer lesions larger than 0.1 cm(3) were found at pathologic examination; 43 were detected by the radiologist. CCCs between imaging and pathologic tumor volume measurements were 0.36 for T2-weighted imaging, and 0.46 and 0.60 for combined T2-weighted and DW MR imaging with ADC cutoffs of 0.0014 and 0.0016 mm(2)/sec, respectively; the CCC of combined T2-weighted and DW MR imaging (ADC cutoff, 0.0016 mm(2)/sec) was significantly higher (P = .006) than that of T2-weighted imaging alone., Conclusion: Adding DW MR to T2-weighted imaging can significantly improve the accuracy of prostate PZ tumor volume measurement., Supplemental Material: http://radiology.rsnajnls.org/cgi/content/full/252/2/449/DC1.

Purpose: To quantify, as a function of average magnetic resonance spectroscopy (MRS) score and tumor volume, the probability that a cancer-suspected lesion has an elevated Gleason grade., Methods and Materials: The data consist of MRS imaging ratios R stratified by patient, lesion (contiguous abnormal voxels), voxels, biopsy and pathologic Gleason grade, and lesion volume. The data were analyzed using a logistic model., Results: For both low and high Gleason score biopsy lesions, the probability of pathologic Gleason score >/=4+3 increases with lesion volume. At low values of R a lesion volume of at least 15-20 voxels is needed to reach a probability of success of 80%; the biopsy result helps reduce the prediction uncertainty. At larger MRS ratios (R > 6) the biopsy result becomes essentially uninformative once the lesion volume is >12 voxels. With the exception of low values of R, for lesions with low Gleason score at biopsy, the MRS ratios serve primarily as a selection tool for assessing lesion volumes., Conclusions: In patients with biopsy Gleason score >/=4+3, high MRS imaging tumor volume and (creatine + choline)/citrate ratio may justify the initiation of voxel-specific dose escalation. This is an example of biologically motivated focal treatment for which intensity-modulated radiotherapy and especially brachytherapy are ideally suited.

In vivo knowledge of the spatial distribution of viable, necrotic, and hypoxic areas can provide prognostic information about the risk of developing metastases and regional radiation sensitivity and may be used potentially for localized dose escalation in radiation treatment. In this study, multimodality in vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging using stereotactic fiduciary markers in the Dunning R3327-AT prostate tumor were performed, focusing on the relationship between dynamic contrast-enhanced (DCE) MRI using Magnevist (Gd-DTPA) and dynamic (18)F-fluoromisonidazole ((18)F-Fmiso) PET. The noninvasive measurements were verified using tumor tissue sections stained for hematoxylin/eosin and pimonidazole. To further validate the relationship between (18)F-Fmiso and pimonidazole uptake, (18)F digital autoradiography was performed on a selected tumor and compared with the corresponding pimonidazole-stained slices. The comparison of Akep values (kep = rate constant of movement of Gd-DTPA between the interstitial space and plasma and A = amplitude in the two-compartment model (Hoffmann U, Brix G, Knopp MV, Hess T and Lorenz WJ (1995). Magn Reson Med 33, 506-514) derived from DCE-MRI studies and from early (18)F-Fmiso uptake PET studies showed that tumor vasculature is a major determinant of early (18)F-Fmiso uptake. A negative correlation between the spatial map of Akep and the slope map of late (last 1 hour of the dynamic PET scan) (18)F-Fmiso uptake was observed. The relationships between DCE-MRI and hematoxylin/eosin slices and between (18)F-Fmiso PET and pimonidazole slices confirm the validity of MRI/PET measurements to image the tumor microenvironment and to identify regions of tumor necrosis, hypoxia, and well-perfused tissue.

Dedicated small-animal imaging devices, e.g. positron emission tomography (PET), computed tomography (CT) and magnetic resonance imaging (MRI) scanners, are being increasingly used for translational molecular imaging studies. The objective of this work was to determine the positional accuracy and precision with which tumors in situ can be reliably and reproducibly imaged on dedicated small-animal imaging equipment. We designed, fabricated and tested a custom rodent cradle with a stereotactic template to facilitate registration among image sets. To quantify tumor motion during our small-animal imaging protocols, 'gold standard' multi-modality point markers were inserted into tumor masses on the hind limbs of rats. Three types of imaging examination were then performed with the animals continuously anesthetized and immobilized: (i) consecutive microPET and MR images of tumor xenografts in which the animals remained in the same scanner for 2 h duration, (ii) multi-modality imaging studies in which the animals were transported between distant imaging devices and (iii) serial microPET scans in which the animals were repositioned in the same scanner for subsequent images. Our results showed that the animal tumor moved by less than 0.2-0.3 mm over a continuous 2 h microPET or MR imaging session. The process of transporting the animal between instruments introduced additional errors of approximately 0.2 mm. In serial animal imaging studies, the positioning reproducibility within approximately 0.8 mm could be obtained.

Purpose: To retrospectively measure the mean apparent diffusion coefficient (ADC) with diffusion-weighted magnetic resonance (MR) imaging and the mean metabolic ratio (MET) with three-dimensional (3D) hydrogen 1 ((1)H) MR spectroscopic imaging in regions of interest (ROIs) drawn over benign and malignant peripheral zone (PZ) prostatic tissue and to assess ADC, MET, and combined ADC and MET for identifying malignant ROIs, with whole-mount histopathologic examination as the reference standard., Materials and Methods: The institutional review board approved this HIPAA-compliant retrospective study and issued a waiver of informed consent. From among 61 consecutive patients with prostate cancer, 38 men (median age, 61 years; range, 42-72 years) who underwent 1.5-T endorectal MR imaging before radical prostatectomy and who fulfilled all inclusion criteria of no prior hormonal or radiation treatment and at least one PZ lesion (volume, >0.1 cm(3)) at whole-mount pathologic examination were included. ADC maps were generated from diffusion-weighted MR imaging data, and MET maps of (choline plus polyamine plus creatine)/citrate were calculated from 3D (1)H MR spectroscopic imaging data. ROIs in the PZ identified by matching pathologic slides with T2-weighted images were overlaid on MET and ADC maps. Areas under the receiver operating characteristic curves (AUCs) were used to evaluate accuracy., Results: The mean ADC +/- standard deviation, (1.39 +/- 0.23) x 10(-3) mm(2)/sec, and mean MET (0.92 +/- 0.32) for malignant ROIs differed significantly from the mean ADC, (1.69 +/- 0.24) x 10(-3) mm(2)/sec, and mean MET (0.73 +/- 0.18) for benign ROIs (P < .001 for both). In distinguishing malignant ROIs, combined ADC and MET (AUC = 0.85) performed significantly better than MET alone (AUC = 0.74; P = .005) and was also better than ADC alone (AUC = 0.81), although the difference was not statistically significant (P = .09)., Conclusion: The combination of ADC and MET performs significantly better than MET for differentiating between benign and malignant ROIs in the PZ., ((c) RSNA, 2008.)

Proton Magnetic Resonance Spectroscopic Imaging (MRSI) permits a non-invasive assessment of metabolites in the prostate gland. This article reviews the assessment of choline-containing compounds, citrate, and polyamines as markers for prostate tumor detection and aggressiveness.

Purpose: To characterize benign and malignant prostate peripheral zone (PZ) tissue retrospectively by using a commercial magnetic resonance (MR) spectroscopic imaging package and incorporating the choline plus creatine-to-citrate ratio ([Cho + Cr]/Cit) and polyamine (PA) information into a statistically based voxel classification procedure., Materials and Methods: The institutional review board approved this HIPAA-compliant study and waived the requirement for informed consent. Fifty men (median age, 60 years; range, 44-69 years) with untreated biopsy-proved prostate cancer underwent combined endorectal MR imaging and MR spectroscopic imaging. Commercial software was used to acquire and process MR spectroscopic imaging data. The (Cho + Cr)/Cit and the PA level were tabulated for each voxel. The PA level was scored on a scale of 0 (PA undetectable) to 2 (PA peak as high as or higher than Cho peak). Whole-mount step-section histopathologic analysis constituted the reference standard. Classification and regression tree analysis in a training set generated a decision-making tree (rule) for classifying voxels as malignant or benign, which was validated in a test set. Receiver operating characteristic and generalized estimating equation regression analyses were used to assess accuracy and sensitivity, respectively., Results: The median (Cho + Cr)/Cit was 0.55 (mean +/- standard deviation, 0.59 +/- 0.03) in benign and 0.77 (mean, 1.08 +/- 0.20) in malignant PZ voxels (P = .027). A significantly higher percentage of benign (compared with malignant) voxels had higher PA than choline peaks (P < .001). In the 24-patient training set (584 voxels), the rule yielded 54% sensitivity and 91% specificity for cancer detection; in the 26-patient test set (667 voxels), it yielded 42% sensitivity and 85% specificity. The percentage of cancer in the voxel at histopathologic analysis correlated positively (P < .001) with the sensitivity of the classification and regression tree rule, which was 75% in voxels with more than 90% malignancy., Conclusion: The statistically based classification rule developed indicated that PAs have an important role in the detection of PZ prostate cancer. With commercial software, this method can be applied in clinical settings.

Objective: To design new models that combine clinical variables and biopsy data with magnetic resonance imaging (MRI) and MR spectroscopic imaging (MRSI) data, and assess their value in predicting the probability of insignificant prostate cancer., Patients and Methods: In all, 220 patients (cT stage T1c or T2a, prostate-specific antigen level <20 ng/mL, biopsy Gleason score 6) had MRI/MRSI before surgery and met the inclusion criteria for the study. The probability of insignificant cancer was recorded retrospectively and separately for MRI and combined MRI/MRSI on a 0-3 scale (0, definitely insignificant; - 3, definitely significant). Insignificant cancer was defined from surgical pathology as organ-confined cancer of

The genetic transfer of antigen receptors is a powerful approach to rapidly generate tumor-specific T lymphocytes. Unlike the physiologic T-cell receptor, chimeric antigen receptors (CARs) encompass immunoglobulin variable regions or receptor ligands as their antigen recognition moiety, thus permitting T cells to recognize tumor antigens in the absence of human leukocyte antigen expression. CARs encompassing the CD3zeta chain as their activating domain induce T-cell proliferation in vitro, but limited survival. The requirements for genetically targeted T cells to function in vivo are less well understood. We have, therefore, established animal models to assess the therapeutic efficacy of human peripheral blood T lymphocytes targeted to prostate-specific membrane antigen (PSMA), an antigen expressed in prostate cancer cells and the neovasculature of various solid tumors. In vivo specificity and antitumor activity were assessed in mice bearing established prostate adenocarcinomas, using serum prostate-secreted antigen, magnetic resonance, computed tomography, and bioluminescence imaging to investigate the response to therapy. In three tumor models, orthotopic, s.c., and pulmonary, we show that PSMA-targeted T cells effectively eliminate prostate cancer. Tumor eradication was directly proportional to the in vivo effector-to-tumor cell ratio. Serial imaging further reveals that the T cells must survive for at least 1 week to induce durable remissions. The eradication of xenogeneic tumors in a murine environment shows that the adoptively transferred T cells do not absolutely require in vivo costimulation to function. These results thus provide a strong rationale for undertaking phase I clinical studies to assess PSMA-targeted T cells in patients with metastatic prostate cancer.

Cellular senescence has been theorized to oppose neoplastic transformation triggered by activation of oncogenic pathways in vitro, but the relevance of senescence in vivo has not been established. The PTEN and p53 tumour suppressors are among the most commonly inactivated or mutated genes in human cancer including prostate cancer. Although they are functionally distinct, reciprocal cooperation has been proposed, as PTEN is thought to regulate p53 stability, and p53 to enhance PTEN transcription. Here we show that conditional inactivation of Trp53 in the mouse prostate fails to produce a tumour phenotype, whereas complete Pten inactivation in the prostate triggers non-lethal invasive prostate cancer after long latency. Strikingly, combined inactivation of Pten and Trp53 elicits invasive prostate cancer as early as 2 weeks after puberty and is invariably lethal by 7 months of age. Importantly, acute Pten inactivation induces growth arrest through the p53-dependent cellular senescence pathway both in vitro and in vivo, which can be fully rescued by combined loss of Trp53. Furthermore, we detected evidence of cellular senescence in specimens from early-stage human prostate cancer. Our results demonstrate the relevance of cellular senescence in restricting tumorigenesis in vivo and support a model for cooperative tumour suppression in which p53 is an essential failsafe protein of Pten-deficient tumours.

Purpose: To prospectively evaluate magnetic resonance (MR) imaging and MR spectroscopy for depiction of local prostate cancer recurrence after external-beam radiation therapy, with step-section pathologic findings as the standard of reference., Materials and Methods: Study received institutional approval, and written informed consent was obtained. Study was compliant with Health Insurance Portability and Accountability Act. Sextant biopsy, digital rectal examination, MR imaging, MR spectroscopy, and salvage radical prostatectomy with step-section pathologic examination were performed in nine patients with increasing prostate-specific antigen levels after external-beam radiation therapy. MR imaging criterion for tumor was a focal nodular region of reduced signal intensity at T2-weighted imaging. MR spectroscopic criteria for tumor were voxels with choline (Cho) plus creatine (Cr) to citrate (Cit) ratio ([Cho + Cr]/Cit) of at least 0.5 or voxels with detectable Cho and no Cit in the peripheral zone. Sensitivity and specificity of sextant biopsy, digital rectal examination, MR imaging, and MR spectroscopy were determined by using a prostate sextant as the unit of analysis. For feature analysis, MR imaging and MR spectroscopic findings were correlated with step-section pathologic findings., Results: MR imaging and MR spectroscopy showed estimated sensitivities of 68% and 77%, respectively, while sensitivities of biopsy and digital rectal examination were 48% and 16%, respectively. MR spectroscopy appears to be less specific (78%) than the other three tests, each of which had a specificity higher than 90%. MR spectroscopic feature analysis showed that a metabolically altered benign gland could be falsely identified as tumor by using MR spectroscopic criteria; further analysis of MR spectroscopic features did not lead to improved MR spectroscopic criteria for recurrent tumor., Conclusion: In summary, MR imaging and MR spectroscopy may be more sensitive than sextant biopsy and digital rectal examination for sextant localization of cancer recurrence after external-beam radiation therapy.

Purpose: To determine whether hydrogen 1 magnetic resonance (MR) spectroscopic imaging can be used to predict aggressiveness of prostate cancer., Materials and Methods: All patients gave informed consent according to an institutionally approved research protocol. A total of 123 patients (median age, 58 years; age range, 40-74 years) who underwent endorectal MR imaging and MR spectroscopic imaging between January 2000 and December 2002 were included. MR imaging and spectroscopy were performed by using combined pelvic phased-array and endorectal probe. Water and lipids were suppressed, and phase-encoded data were acquired with 6.2-mm resolution. Voxels in the peripheral zone were considered suspicious for cancer if (Cho + Cr)/Cit was at least two standard deviations above the normal level, where Cho represents choline-containing compounds, Cr represents creatine and phosphocreatine, and Cit represents citrate. Correlation between metabolite ratio and four Gleason score groups identified at step-section pathologic evaluation (3 + 3, 3 + 4, 4 + 3, and > or =4 + 4) was assessed with generalized estimating equations., Results: Data from 94 patients were included. Pathologic evaluation was used to identify 239 lesions. Overall sensitivity of MR spectroscopic imaging was 56% for tumor detection, increasing from 44% in lesions with Gleason score of 3 + 3 to 89% in lesions with Gleason score greater than or equal to 4 + 4. There was a trend toward increasing (Cho + Cr)/Cit with increasing Gleason score in lesions identified correctly with MR spectroscopic imaging. Tumor volume assessed with MR spectroscopic imaging increased with increasing Gleason score., Conclusion: MR spectroscopic imaging measurement of prostate tumor (Cho + Cr)/Cit and tumor volume correlate with pathologic Gleason score. There is overlap between MR spectroscopic imaging parameters at various Gleason score levels, which may reflect methodologic and physiologic variations. MR spectroscopic imaging has potential in noninvasive assessment of prostate cancer aggressiveness.

The purpose of the study was to determine whether 3D proton magnetic resonance spectroscopic imaging (MRSI) can predict treatment outcome in high risk patients with prostate cancer. Endorectal magnetic resonance imaging (MRI) and 1H-MRSI were performed in 16 patients with prostate cancer who were considered high risk because of clinical stage T3-4, Gleason score>/=8, and/or prostate-specific antigen (PSA) level>20 ng/mL. Patients were treated with chemotherapy/hormone therapy, underwent radical prostatectomy (RP) or radiation therapy, and were followed for PSA relapse (follow-up, 19-43 months). The ratio of choline plus creatine to citrate was used to localize peripheral zone cancer. An MRSI risk score on a scale of 0-3 was derived from the volume and degree of metabolic abnormality. Magnetic resonance spectroscopic imaging risk score, MRI tumor/node (TN) stage, clinical stage, Gleason score, and PSA were used as predictors of pathologic stage in patients treated with RP (n=10) and PSA relapse in all patients. Magnetic resonance imaging TN stage (P<0.01) and MRSI risk score (P<0.05) correlated with pathologic stage, but clinical stage did not (P=0.35). Magnetic resonance imaging TN stage was the only significant predictor of PSA relapse in the univariate analysis (P<0.05). Although the MRSI risk score did not reach significance (P=0.13), 6 patients with a score<0.9 were relapse-free, whereas 7 of 10 patients with a score>0.9 relapsed. Magnetic resonance imaging and MRSI risk assessments agreed in 15 of 16 patients. These preliminary results suggest that tumor metabolic assessment may indicate treatment outcome in high-risk patients with prostate cancer. Although MRSI did not provide added prognostic value to MRI in this small number of patients, MRSI might increase the confidence of the clinician in assessing risk on MRI by contributing supporting metabolic data.

Complete inactivation of the PTEN tumor suppressor gene is extremely common in advanced cancer, including prostate cancer (CaP). However, one PTEN allele is already lost in the vast majority of CaPs at presentation. To determine the consequence of PTEN dose variations on cancer progression, we have generated by homologous recombination a hypomorphic Pten mouse mutant series with decreasing Pten activity: Pten(hy/+) > Pten(+/-) > Pten(hy/-) (mutants in which we have rescued the embryonic lethality due to complete Pten inactivation) > Pten prostate conditional knockout (Pten(pc)) mutants. In addition, we have generated and comparatively analyzed two distinct Pten(pc) mutants in which Pten is inactivated focally or throughout the entire prostatic epithelium. We find that the extent of Pten inactivation dictate in an exquisite dose-dependent fashion CaP progression, its incidence, latency, and biology. The dose of Pten affects key downstream targets such as Akt, p27(Kip1), mTOR, and FOXO3. Our results provide conclusive genetic support for the notion that PTEN is haploinsufficient in tumor suppression and that its dose is a key determinant in cancer progression., Competing Interests: The authors have declared that no conflicts of interest exist.

Purpose: The ability to determine the spatial and metabolic distribution of prostate cancer is essential in assessing initial stage, prognosis, and treatment efficacy. Current markers of tumor progression such as prostate-specific antigen (PSA) do not provide spatial information about tumor extent or regions of high metabolic activity., Experimental Design: This study used the androgen-dependent CWR22 human prostate tumor xenograft in mice to characterize metabolic, PSA, and tumor volume changes that occurred with untreated growth or radiation therapy (XRT). One cohort of mice was studied as the tumor grew to 400 mm(3), whereas a second cohort was treated with a single 20-Gy fraction of radiation and studied before and 1, 2, and 4 days after XRT. In both cohorts, tumor volume, PSA, and choline:water ratios measured by nuclear magnetic resonance were monitored., Results: The CWR22 tumor had an untreated tumor-doubling time of 2.6 +/- 0.6 days (n = 7). In untreated mice, PSA strongly correlated with tumor volume (P < 0.01, R(2) = 0.99). The untreated tumor cohort had a PSA-doubling time of 3.2 +/- 0.6 days. Administration of 20 Gy produced a regrowth delay of >15.8 +/- 4.8 days (n = 6). PSA values after XRT were not correlated with post-XRT tumor volume (P < 0.20, R(2) = 0.02). A constant level of the choline:water ratio (0.010 +/- 0.001; n = 22, R(2) = 0.007, P < 0.3) was observed during the course of untreated tumor growth. A statistically significant (P < 0.04, one-tailed t test) 42% decrease in the choline:water ratio at 24 h after administration of XRT preceded observable changes in PSA., Conclusions: Nuclear magnetic resonance spectroscopy provided a method with which to monitor metabolic changes of tumor response to XRT that preceded and predicted PSA and tumor volume changes.

Purpose: To determine whether cancers of the prostate transition zone (TZ) possess a unique metabolic pattern by which they may be identified at proton magnetic resonance (MR) spectroscopic imaging., Materials and Methods: Findings in 40 patients who underwent combined endorectal MR imaging and hydrogen 1 MR spectroscopic imaging before radical prostatectomy and who had TZ tumor identified subsequently at step-section pathologic analysis were retrospectively reviewed. Within this population, a subset of 16 patients whose TZ tumor had a largest diameter of 1 cm or greater and was included in the MR spectroscopic imaging excitation volume was identified. In these 16 patients, the ratios of choline-containing compounds (Cho) and creatine/phosphocreatine (Cr) to citrate (Cit) (ie, [Cho + Cr]/Cit), Cho/Cr, and Cho/Cit were compared in tumor and control tissues. The presence of only Cho and the absence of all metabolites were also assessed., Results: The mean values of (Cho + Cr)/Cit, Cho/Cr, and Cho/Cit were different between TZ cancer and control tissues (P =.001, P =.003, and P =.001, respectively; Wilcoxon signed rank test). Nine (56%) of 16 patients had at least one tumor voxel in which Cho comprised the only detectable peak, while no control voxels showed only Cho (P =.008, McNemar test). The percentage of voxels in which no metabolites were detected did not differ between tumor and control tissues (P =.134, McNemar test)., Conclusion: TZ cancer has a metabolic profile that is different from that of benign TZ tissue; however, the broad range of metabolite ratios observed in TZ cancer precludes the use of a single ratio to differentiate TZ cancer from benign TZ tissue., (Copyright RSNA, 2003)

Expression of neutral endopeptidase (NEP) 24.11 is diminished in metastatic, androgen-independent prostate cancers (PCs; C. N. Papandreou et al., NAT: MED:, 4: 50--57, 1998). To determine the effects on androgen-independent PC cells of overexpressing cell-surface NEP, an inducible tetracycline-regulatory gene expression system was used to stably introduce and express the NEP gene in androgen-independent TSU-Pr1 cells generating WT-5 cells, which expressed high levels of enzymatically active NEP protein when cultured in the absence of tetracycline. TN12 cells, which contain the identical vectors without the NEP gene and do not express NEP, were used as control. Expression of NEP in WT-5 cells after removal of tetracycline from the media resulted in a >80% inhibition in cell proliferation over a 1-week period (P < 0.005) compared with control cells. Tumor formation occurred in the prostate glands of orthotopically injected athymic mice killed at 30 days in 4 of 5 mice that were given injections of 2 x 10(6) WT-5 cells and were fed doxycycline (NEP suppressed), and in all mice that were given injections of TN12 cells and were fed with or without doxycycline. In contrast, only 1 of 5 mouse prostates developed a tumor in mice that were given injections of WT-5 cells and that did not receive doxycycline. Analysis of the mechanisms of NEP-induced growth suppression revealed that NEP expression in WT-5 cells induced a 4-fold increase in the number of PC cells undergoing apoptosis, and increased the expression of p21 tumor suppressor gene protein and the level of unphosphorylated retinoblastoma protein as determined by Western blot. Flow cytometric analysis show that induced NEP expression in WT-5 cells resulted in a G(1) cell cycle arrest. These data show that NEP can inhibit PC cell growth and tumorigenicity and suggest that NEP has potential as therapy for androgen-independent PC.

Since the first suggested use of nuclear magnetic resonance (NMR) for detecting cancer, followed by the demonstration of the feasibility of imaging based on the NMR signal in 1973, magnetic resonance imaging (MRI) has become the modality of choice for a variety of clinical applications. Subsequently, the use of NMR spectroscopy (MRS) to detect the presence of different metabolites in vivo has provided unique opportunities for obtaining physiological and biochemical information. More recently, improvements in NMR equipment (magnet, electronics, computers, gradients coils, radiofrequency coils) and pulse sequences (software) have further improved these capabilities. The distinctions between MRI and MRS have begun to blur as new techniques emerge that combine imaging and spectroscopy, generating MRS images of a variety of metabolites. This review provides a brief overview of recent developments in MRS studies pertinent to the clinical evaluation of prostate cancer. The paper has been divided into three parts: a brief qualitative theoretical section about MRS, a review of in vitro studies, and a discussion of the clinical studies of the human prostate.

Purpose: Recent studies have demonstrated that magnetic-resonance spectroscopic imaging (MRSI) of the prostate may effectively distinguish between regions of cancer and normal prostatic epithelium. This diagnostic imaging tool takes advantage of the increased choline plus creatine versus citrate ratio found in malignant compared to normal prostate tissue. The purpose of this study is to describe a novel brachytherapy treatment-planning optimization module using an integer programming technique that will utilize biologic-based optimization. A method is described that registers MRSI to intraoperative-obtained ultrasound images and incorporates this information into a treatment-planning system to achieve dose escalation to intraprostatic tumor deposits., Methods: MRSI was obtained for a patient with Gleason 7 clinically localized prostate cancer. The ratios of choline plus creatine to citrate for the prostate were analyzed, and regions of high risk for malignant cells were identified. The ratios representing peaks on the MR spectrum were calculated on a spatial grid covering the prostate tissue. A procedure for mapping points of interest from the MRSI to the ultrasound images is described. An integer-programming technique is described as an optimization module to determine optimal seed distribution for permanent interstitial implantation. MRSI data are incorporated into the treatment-planning system to test the feasibility of dose escalation to positive voxels with relative sparing of surrounding normal tissues. The resultant tumor control probability (TCP) is estimated and compared to TCP for standard brachytherapy-planned implantation., Results: The proposed brachytherapy treatment-planning system is able to achieve a minimum dose of 120% of the 144 Gy prescription to the MRS positive voxels using (125)I seeds. The preset dose bounds of 100-150% to the prostate and 100-120% to the urethra were maintained. When compared to a standard plan without MRS-guided optimization, the estimated TCP for the MRS-optimized plan is superior. The enhanced TCP was more pronounced for smaller volumes of intraprostatic tumor deposits compared to estimated TCP values for larger lesions., Conclusions: Using this brachytherapy-optimization system, we could demonstrate the feasibility of MRS-optimized dose distributions for (125)I permanent prostate implants. Based on probability estimates of anticipated improved TCP, this approach may have an impact on the ability to safely escalate dose and potentially improve outcome for patients with organ-confined but aggressive prostatic cancers. The magnitude of the TCP enhancement, and therefore the risks of ignoring the MR data, appear to be more substantial when the tumor is well localized; however, the gain achievable in TCP may depend quite considerably on the MRS tumor-detection efficiency.

Purpose: Recent studies have demonstrated that magnetic resonance spectroscopic imaging (MRSI) of the prostate may effectively distinguish between regions of cancer and normal prostatic epithelium. This diagnostic imaging tool takes advantage of the increased choline and creatine versus citrate ratio found in malignant, compared with normal, prostate tissue. The purpose of this report is to present our initial experience integrating MRSI data into an intraoperative computer-based optimization planning system for prostate cancer patients who underwent permanent interstitial I 125 implantation. The goal of this approach was to achieve dose escalation to intraprostatic tumor deposits on the basis of MRSI findings without exceeding the tolerance of adjacent normal tissue structures., Materials and Methods: MRSI was obtained before surgery for four consecutive patients with clinically localized prostate cancer. The ratios of choline and citrate for the prostate were analyzed, and regions in which malignant cells were suspected to be present were identified. These ratios were calculated on a spatial grid overlying the axial MRSI of the prostate. MRSI coordinates containing these suspicious regions were registered to the intraoperative ultrasound images. A computer-based treatment planning system, which relied on a genetic algorithm, was used to determine the optimal seed distribution necessary to achieve maximal target volume coverage with the prescription dose and to maintain urethra and rectal doses within tolerance ranges. The treatment planning system was specifically designed to escalate the dose to MRS-positive voxels while at the same time achieving preferential sparing of surrounding normal tissues. Patients underwent transperineal interstitial implantation with I 125 by use of this intraoperatively generated plan. Postimplant computed tomographic scans were performed on the same day of the procedure in all cases, and dosimetric guidelines of the American Brachytherapy Society were used to assess implant quality., Results: Based on the postimplant computed tomographic evaluation, the intraoperative optimization treatment planning program was able to achieve a minimum dose of 139% to 192% of the 144-Gy prescription dose to the MRS-positive voxels. The percentage of the prostate volume receiving 100% of the prescription dose ranged from 92% to 97%, and the dose delivered to 90% of the target for the target volume ranged from 96% to 124%. Despite the dose escalation achieved for the positive voxels, the urethral and rectal doses were maintained within tolerance ranges. The average and maximal rectal doses ranged from 28% to 43% and 69% to 115% of the prescription dose, respectively. The average and maximal urethral doses ranged from 66% to 144% and 118% to 166% of the prescription dose, respectively., Conclusions: Using this brachytherapy optimization system, we could demonstrate the feasibility of MRS-optimized dose distributions for I 125 permanent prostate implants. This approach may have an impact on the ability to select regions within the prostate to safely employ dose escalation for patients treated with permanent interstitial implantation and to improve outcome for patients with organ-confined prostatic cancers.

Twenty-five patients with prostatic cancer were prospectively examined with a prototype endorectal surface coil featuring a birdcage resonator circuit design. The purpose was to determine the safety of an intracavitary probe for magnetic resonance (MR) imaging of the pelvis that incorporates the "inside-out" characteristics of a volume coil design and allows high-resolution MR imaging of the prostate and potentially serves as an alternative to single-loop intracavitary surface coils. Clinically useful images supplementing images obtained with the body or external surface coils were obtained with the prototype probe. It was tolerated by all patients enrolled in the study, and none experienced side effects. The cylindrically symmetric sensitivity profile of the probe allowed identification of prostate tumors and pelvic lymph node and bone metastases. Volume-type coils may improve endopelvic MR imaging when used alone or in combination with external coil systems.