Purpose: We evaluate the usefulness of pretreatment (111)Indium capromab pendetide (ProstaScint (TM)) planar imaging (immunoscintigraphy) plus single photon emission tomography co-registration with computerized tomography scans to detect occult metastatic disease and predict for biochemical failure, in a cohort of patients with a clinical diagnosis of localized adenocarcinoma of the prostate referred for primary radiotherapy.Materials and Methods: Patients were followed after radiotherapy for evidence of biochemical failure using 2 criteria of prostate specific antigen clinical nadir +2 ng/ml and American Society for Therapeutic Radiology and Oncology Consensus definitions. Median followup was 58.8 months (mean 64.8). Clinical risk factors defined 3 risk groups of high (51), intermediate (72) and low (116).Results: Overall biochemical failure was 18.3% vs 11.8% by the 2-BFC at 8-year actuarial analysis with 58.8 months median followup. By the CN +2 definition the control date for the cohort is 34.8 months. Pretreatment SPECT/CT suggested prostate cancer metastasis (22), seminal vesicle extension (20) and organ confined disease (197). Biochemical failure in patients having extra-periprostatic metastatic prostate cancer, seminal vesicle extension and organ confined disease uptake on SPECT/CT was 43.2%, 16.0% vs 14.7% (p = 0.0006); and 33.3%, 15.0% vs 8.7% (p = 0.0017) by the 2-BFC, respectively. Cox multiple regression analysis demonstrated that a finding of extra-periprostatic metastatic prostate on SPECT/CT significantly predicted a 4.2-fold greater risk (p = 0.0012) and a 4.5-fold greater risk (p = 0.0011) of failure by the 2-BFC than organ confined disease adjusting for treatment and risk group.Conclusions: Unconfirmed findings of extra-periprostatic metastatic prostate cancer on SPECT/CT immunoscintigraphy independently and significantly predicted an increased risk of biochemical failure in patients presenting for radiotherapy with a clinical diagnosis of localized prostate cancer.

OBJECTIVE: To evaluate SPECT/CT Capromab pendetide as a lymph node staging tool for the prediction of biochemical disease free survival (bDFS) in patients prior to definitive radiation therapy for prostate cancer.METHODS: 239 patients with clinical T1c-T3b NxMO prostate cancer were evaluated for lymph node status using co-registered SPECT/CT Capromab pendetide (SPECT/CT) image sets prior to undergoing primary image guided radiation therapy (IGRT) seed implant (SI).Median follow-up was 47.2 months (range 24.8-96.1 ).Patients identified with local vs.distant disease by SPECT/CT were followed for bDFS post-definitive radiation therapy using either Sl-alone, or external beam radiation plus Slboost (EBRT +SI).Patients with distant SPECT/CT findings were assumed to represent possible false positive findings, when not confirmed by secondary assessment.At the clinical discretion of the Urologist, a total of 65 patients underwent node sampling and 50 received neoadjuvant hormone therapy.Biochemical disease free survival (bDFS) was calculated using 3 failure criteria: ASTRO consensus (ASTRO) definition, PSA ~ 1.0 ng/ml and PSA ~ 0.5 ng/ml after nadir.RESULTS: In univariate Cox regression analysis, SPECT/CT distant findings were found to be statistically significant predictors of bDFS in both the entire cohort and in the hormonal na"ive sub-population.For the entire cohort, 217 patients with local and 22 with extraperiprostatic disease by SPECT/CT evaluation had a 7-year bDFS of 90.6% and 66.1% (p = 0.0003); 87.1% and 45.5% (p < 0.0001); 85.8% and 43.8% (p < 0.0001), by the 3 criteria: ASTRO, PSA ~ 1.0 ng/ml, and PSA ~ 0.5 ng/ml after nadir, respectively.For hormonal na"ive patients, the local (n=171) and distant (n =18) subsets, 7-year bDFS rates were 91.6% and 64.2% (p = 0.0004); 88.4% and 31.0%(p = 0.0001); 86.7% and 30.0%(p < 0.0001) by the 3 criteria, respectively.On multivariate Cox regression analysis, SPECT/CT findings significantly predicted for bDFS.The hazard ratio for patients with distant disease by SPECT/CT was found to be 3-fold greater (p = 0.020) for the entire cohort, and 4-fold greater (p = 0.015) for the hormonal na"lve sub-population; with respect to bDFS failure using ASTRO criteria, when compared to those with local disease, after controlling for all confounding factors.CONCLUSIONS: SPECT/CT Capromab pendetide was found beneficial for patient selection prior to local therapy by independently predicting bDFS.SPECT/CT may predict for the benefit of long-term hormonal therapy for patients with distant findings.

Purpose: We determined the prognostic role, if any, of the ProstaScint(TM) (111)indium-capromab pendetide scan before salvage radiotherapy for biochemical recurrence after RP for localized prostate cancer.Materials and Methods: We reviewed the records of 649 patients who underwent a ProstaScint(TM) scan from 1998 to 2004. A total of 44 patients were identified who had biochemical recurrence after RP and underwent a ProstaScint(TM) scan immediately before salvage radiotherapy. All patients received salvage radiotherapy to the prostatic bed unless pelvic lymph node uptake was identified on the scan, resulting in initial whole pelvic radiotherapy with 45 Gy, followed by a conformal boost to the prostate bed in 6. The median salvage radiotherapy dose to the prostate bed was 72 Gy. Patient demographics, pathological information, PSA values and ProstaScint(TM) results were collected retrospectively. The majority of ProstaScint(TM) scans were digitally fused with noncontrast pelvic computerized tomography images for interpretation. PSA progression after radiotherapy was defined using American Society for Therapeutic Radiation and Oncology criteria.Results: At a mean followup of 22 months 43 of 44 patients (97%) experienced a PSA decrease after salvage radiotherapy with a mean PSA nadir of 0.16 ng/ml compared to a mean pre-radiotherapy PSA of 1.7 ng/ml. Of the 44 patients 15 (34%) showed post-radiotherapy PSA progression. When the entire cohort was analyzed, patients with negative ProstaScint(TM) scans had statistically lower post-radiotherapy PSA progression rates than patients with positive scans (I of 10 or 10% vs 14 of 34 or 41%, p = 0.026). Patients with negative ProstaScint(TM) results were also statistically more likely to have a pre-radiotherapy PSA of less than 1.0 ng/ml (p = 0.005), no seminal vesicle involvement (p = 0.006), a greater mean PSA doubling time (p = 0.008) and received no hormone therapy (p = 0.003). When patients with pre-radiotherapy PSA less than 1.0 ng/ml were analyzed, a negative ProstaScint(TM) scan suggested but did not provide a statistically significant advantage over pre-radiotherapy PSA alone for predicting post-radiotherapy PSA progression (1 of 9 or 11% for negative vs 5 of 15 or 33% for positive scans, p = 0.20).Conclusions: Our early experience supports an improved prognosis in patients receiving salvage pelvic radiotherapy for biochemical recurrence after RP who have a negative pre-radiotherapy ProstaScint(TM) scan. However, this finding is not necessarily independent of pre-radiotherapy PSA.

Accurate characterization of prostate cancer is crucial for treatment planning and patient management. Non-invasive SPECT imaging using a radiolabeled monoclonal antibody, 111In-labeled capromab pendetide, offers advantage over existing means for prostate cancer diagnosis and staging. However, there are difficulties associated with the interpretation of these SPECT images. In this study, we developed a 3D surface-volume hybrid rendering method that utilizes multi-modality image data to facilitate diagnosis of prostate cancer. SPECT and CT or MRI (or both) images were aligned either manually or automatically. 3D hybrid rendering was implemented to blend prostate tumor distribution from SPECT in pelvis with anatomic structures from CT/MRI. Feature extraction technique was also implemented within the hybrid rendering for tumor uptake enhancement. Autoradiographic imaging and histological evaluation were performed to correlate with the in-vivo SPECT images. Warping registration of histological sections was carried out to compensate the deformation of histology slices during fixation to help the alignment between histology and in-vivo images. Overall, the rendered volumetric evaluation of prostate cancer has the potential to greatly increase the confidence in the reading of radiolabeled monoclonal antibody scans, especially in patients where there is a high suspicion of prostate tumor metastasis.

RATIONALE AND OBJECTIVES:Three-dimensional (3D) nonrigid image registration for potential applications in prostate cancer treatment and interventional magnetic resonance (iMRI) imaging-guided therapies were investigated.MATERIALS AND METHODS:An almost fully automated 3D nonrigid registration algorithm using mutual information and a thin plate spline (TPS) transformation for MR images of the prostate and pelvis were created and evaluated. In the first step, an automatic rigid body registration with special features was used to capture the global transformation. In the second step, local feature points (FPs) were registered using mutual information. An operator entered only five FPs located at the prostate center, left and right hip joints, and left and right distal femurs. The program automatically determined and optimized other FPs at the external pelvic skin surface and along the femurs. More than 600 control points were used to establish a TPS transformation for deformation of the pelvic region and prostate. Ten volume pairs were acquired from three volunteers in the diagnostic (supine) and treatment positions (supine with legs raised).RESULTS:Various visualization techniques showed that warping rectified the significant pelvic misalignment by the rigid-body method. Gray-value measures of registration quality, including mutual information, correlation coefficient, and intensity difference, all improved with warping. The distance between prostate 3D centroids was 0.7 +/- 0.2 mm after warping compared with 4.9 +/- 3.4 mm with rigid-body registration.CONCLUSION:Semiautomatic nonrigid registration works better than rigid-body registration when patient position is changed greatly between acquisitions. It could be a useful tool for many applications in the management of prostate.

We are investigating interventional MRI (iMRI) guided radiofrequency thermal ablation for the minimally invasive treatment of the prostate cancer. Nuclear medicine can detect and localize tumor in the prostate not reliably seen in MRI. We intend to combine the advantages of functional images such as nuclear medicine SPECT with iMRI-guided treatments. Our concept is to first register the low-resolution SPECT with a high-resolution MRI volume. Then by registering the high-resolution MR image with live-time iMRI acquisitions, we can, in turn, map the functional data and high-resolution anatomic information to live-time iMRI images for improved tumor targeting. For the first step, we used a three-dimensional mutual information registration method. For the latter, we developed a robust slice to volume (SV) registration algorithm with special features. The concept was tested using image data from three patients and three volunteers. The SV registration accuracy was 0.4 mm /spl plusmn/ 0.2 mm as compared to our volume- to-volume registration that was previously shown to be quite accurate for these image pairs. With our image registration and fusion software, simulation experiments show that it is quite feasible to incorporate SPECT and high-resolution MRI into the iMRI-guided minimally invasive treatment procedures.

METHODS: In 191 consecutive patients undergoing retropubic RP with pelvic lymphadenectomy and without evidence of lymph node involvement in the final histological examination (pNO), the radiologic-pathologic correlation was evaluated using a pMRI.Predictive study variables included clinical TNM classification, preoperative serum PSA, biopsy Gleason score, and pMRI findings.The predicted result included in analysis was PSA failure (PSA2:0.lng/ml).The predicted ability of ANNA with several parameters for a set of 150 randomly selected test data was compared with those of Cox regression analysis and "Kattan nomogram" by area under the receiver operating characteristic (ROC) curve analysis.No adjuvant hormonal or radiation therapy was given before PSA failure.RESULTS: Fifty-seven patients (30%) failed at a median follow-up of 64 (mean: 61, range: 2-86) months Overall accuracy of the ANNA, Cox regression and Kattan nomogram were 90%, 72% and 73% for prediction of disease recurrence 5 years after RP, respectively.The area under the ROC curve of ANNA (0.897:'::0.063)was significantly larger (p< 0.05) than those for Cox regression (0.785:'::0.060)and Kattan nomogram (0.733:'::0.061).The Gleason score represented the most influential predictor (relative weight: 2.5) of disease recurrence, followed by pMRI findings (2.2), and PSA (2.0).CONCLUSIONS: ANNA is superior from regression models to predict accurately disease recurrence in more than 90% of the test set patients.The relative importance of pMRI findings and the utility of ANNA to predict the biochemical failure in individual patient referred for RP or other curative treatments must be confirmed in a prospective trial.

RATIONALE AND OBJECTIVES:To aid in surgical and radiation therapy planning for prostate adenocarcinoma, a general-purpose automatic registration method that is based on mutual information was used to align magnetic resonance (MR) images and single photon emission computed tomographic (SPECT) images of the pelvis and prostate. MATERIALS AND METHODS:The authors assessed the effects of various factors on alignment between pairs of MR and SPECT images, including the use of particular pulse sequences in MR imaging, image voxel intensity scaling, the use of different regions on the MR-SPECT histogram, spatial masking of nonoverlapping visual data between images, and multiresolution optimization. A mutual information algorithm was used as the cost function for automatic registration. Automatic registration was deemed acceptable when it resulted in a transformation with less than 2 voxel units (6 mm) difference in translation and less than 2 degree difference in rotation from that obtained with manual registration performed independently by nuclear medicine radiologists. RESULTS:Paired sets of MR and SPECT image volumes from four of five patients were successfully registered. For successful registration, MR images must be optimal and registration must be performed at full spatial resolution and at the full intensity range. Masking, cropping, and the normalization of mutual information, used to register partially overlapping MR-SPECT volumes, were not successful. Multiresolution optimization had little effect on the accuracy and speed of the registration. CONCLUSION:Automatic registration between MR and SPECT images of the pelvis can be achieved when data acquisition and image processing are performed properly. It should prove useful for prostate cancer diagnosis, staging, and treatment planning.

PURPOSE:We have previously presented a technique that fuses ProstaScint and pelvic CT images for the purpose of designing brachytherapy that targets areas at high risk for treatment failure. We now correlate areas of increased intensity seen on ProstaScint-CT fusion images to biopsy results in a series of 7 patients to evaluate the accuracy of this technique in localizing intraprostatic disease.METHODS AND MATERIALS:The 7 patients included in this study were evaluated between June 1998 and March 29, 1999 at Metrohealth Medical Center and University Hospitals of Cleveland in Cleveland, Ohio. ProstaScint and CT scans of each patient were obtained before transperineal biopsy and seed implantation. Each patient's prostate gland was biopsied at 12 separate sites determined independently of Prostascint-CT scan results.RESULTS:When correlated with biopsy results, our method yielded an overall accuracy of 80%: with a sensitivity of 79%, a specificity of 80%, a positive predictive value of 68%, and a negative predictive value of 88%.CONCLUSION:The image fusion of the pelvic CT scan and ProstaScint scan helped identify foci of adenocarcinoma within the prostate that correlated well with biopsy results. These data may be useful to escalate doses in regions containing tumor by either high-dose rate or low-dose rate brachytherapy, as well as by external beam techniques such as intensity modulated radiotherapy (IMRT).