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PURPOSE: We evaluate the usefulness of pretreatment (111)Indium capromab pendetide (ProstaScint) 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.

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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).

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PURPOSE: We present a technique that fuses pelvic CT scans and ProstaScint images to localize areas of disease within the prostate gland to customize prostate implants. Additionally, the acute toxicity results from the first 43 patients treated with this technique are reviewed. METHODS AND MATERIALS: Between 2/97 and 8/98, 43 patients with clinical stage II prostate adenocarcinoma received ultrasound-guided transperineal implantation of I-125 or Pd-103 seeds. The median patient age was 70 years (range 49-79). Prior to treatment, the median Gleason score and prostate-specific antigen (PSA) were 6 (range 3-8) and 7.5 (range 1.8-16.6 ng/mL), respectively. The median follow-up was 10 months (range 2.9-20.4 months). RESULTS: The median PSA value at 10 months is 0.7 ng/mL. Significant acute complications within the first month following implantation included 13 Grade I urinary symptoms, 24 Grade II urinary symptoms, 6 Grade III symptoms, and no Grade IV complications. Beyond 4 months, complications included 12 Grade I urinary symptoms, 17 Grade II urinary symptoms, 1 Grade III, and 1 Grade IV complications. CONCLUSIONS: The image fusion of the pelvic CT scan and ProstaScint scans helped identify regions within the prostate at high risk of local failure, which were targeted with additional seeds during implantation.

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OBJECTIVES: To report the results of a retrospective study of 2290 ProstaScint scans of 2154 patients with prostate carcinoma done at 15 institutions. METHODS: The results were analyzed by logistic regression after stratification of the patients into four groups: group 1, newly diagnosed; group 2, after radical prostatectomy with a rising prostate-specific antigen (PSA) level; group 3, after radiation therapy with a rising PSA level; and group 4, after hormonal therapy. RESULTS: The PSA level and ProstaScint scans positive in the prostate bed (P <0.001) and for pelvic metastases (P <0.001), but not for extrapelvic metastases, correlated significantly in group 1 patients. In group 2, the association for detecting fossa recurrence was weaker (P = 0.033) and was insignificant for pelvic and extrapelvic metastases. Patients in group 3 also exhibited a weak PSA-ProstaScint association for detecting fossa recurrence (P = 0.038), and was insignificant for pelvic and extrapelvic metastases. No significant PSA-ProstaScint correlation was found in patients in group 4 for fossa recurrence, pelvic or extrapelvic metastases. The distribution of positive ProstaScint results among the prostate/prostate bed, pelvic nodes, and extrapelvic nodes was nearly equal for all groups, except that a significantly greater percentage of extrapelvic metastases was found in the hormonal group (group 4). The ProstaScint results were independent of the Gleason score for 260 patients before and 285 patients after therapy. CONCLUSIONS: The results of this study underscore the complementary diagnostic value of ProstaScint to PSA level and Gleason score as an independent indicator of prostate cancer recurrence and metastases and in identifying extrapelvic metastases in both newly diagnosed and recurrent prostate cancer.

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BACKGROUND: ProstaScint (Cytogen Corporation, Princeton, NJ) murine monoclonal antibody imaging is FDA-approved for imaging of prostate cancer patients at high risk for metastatic disease and patients postprostatectomy with a rising serum prostate-specific antigen (PSA) level. ProstaScint is a murine monoclonal antibody which targets prostate-specific membrane antigen (PSMA). PSMA expression is upregulated in primary and metastatic prostate cancer. FDA Cytogen (Princeton, NJ) protocol studies using 111indium-labeled ProstaScint revealed correlation between areas of increased concentration in the prostate and biopsy-proven tumors in patients imaged pretherapy. METHODS: In our study, four transverse, single-photon emission tomography (SPECT) images were isolated and regions of interest were selected and correlated with pretherapy prostate biopsy results. Prostate cancer and normal tissue prostate/muscle background (P/M) ratios were derived, so that postprostatectomy/radiation therapy patients could be evaluated for the presence of residual prostate cancer. Twenty-three pretherapy prostate cancer patients with quadrant/sextant biopsies had SPECT 96-hr 111indium ProstaScint pelvic images. The four transverse 1-cm slices above the midline penile blood pool were chosen, and four to six 27-30-pixel regions of interest were placed over the prostate bed. The background muscle region of interest was placed over the external obturator muscle region. The P/M ratio was calculated and compared to the quadrant/sextant prostatic biopsy result. The same procedure was applied to 17 posttherapy prostate cancer patients with rising PSA. RESULTS: In the 23 pretherapy prostate cancer patients, there was a correlation between the P/M ratio of at least 3.0 in 32 of 35 prostatic cancer biopsy regions, and there was correlation with P/M ratios less than 3.0 in 82 of 89 negative biopsy regions. Seventeen posttherapy patients underwent ProstaScint studies. Six underwent biopsy, with typically one biopsy site per patient. All 6 had P/M ratios greater than 3.0 in the biopsied region. Five out of six biopsies revealed residual prostate cancer. CONCLUSIONS: A prostate/muscle ratio was developed from 111indium ProstaScint regions of interest obtained on 1-cm SPECT transverse slices through the prostate bed in 23 patients preprostatic cancer therapy. A P/M ratio above 3.0 correlated in the majority of positive cases, and a P/M ratio below 3.0 was demonstrated in negative prostatic biopsy cases. The P/M ratio of above 3.0 or below 3.0 also separated those posttherapy prostate cancer patients with rising PSA who had residual prostate carcinoma in the prostate bed.

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To evaluate whether In-111 capromab pendetide (an antibody conjugate directed to a glycoprotein found primarily on the cell membrane of prostate tissue) radioimmunoscintigraphy can localize residual or metastatic prostatic carcinoma in 15 patients after prostatectomy and lymphadenectomy for prostatic carcinoma with rising serum prostate-specific antigen. One patient with 0.6 ng/ml serum prostate-specific antigen had normal imaging results and 14 patients had scintigraphic evidence of residual prostatic bed or metastatic prostatic carcinoma. Two patients with borderline abnormal bone scans had abnormal activity in the same regions on In-111 capromab pendetide images. All patients had negative radiographic abdominal and pelvic cross-sectional prestudy images, and there were no adverse effects related to In-111 capromab pendetide infusion and little human antimouse antibody response.

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Technetium-99m-sestamibi (MIBI) is a new radionuclide for imaging parathyroid tissue. The purpose of this study was to evaluate parathyroid localization using single radiotracer, dual-phase MIBI scintigraphy and to compare the results to ultrasonography. Twenty-one patients with hyperparathyroidism underwent dual-phase scintigraphy using 25 mCi MIBI and high resolution ultrasonography before parathyroidectomy. Scan results were correlated with size, weight, location, and histopathology of excised parathyroid glands, thyroid abnormalities, and cost. Seventeen patients were female, five had secondary or tertiary hyperparathyroidism, and three had a previous parathyroid exploration. Twenty patients (95%) were cured, 14 with a single and 1 with a double adenoma, and 5 of 6 patients with generalized hyperplasia. There were no false positive MIBI scans and one false positive ultrasound study, despite associated thyroid nodules in 29 per cent of patients. The sensitivity of MIBI and ultrasound in the identification of adenomas was 87 per cent versus 57 per cent (P = 0.046), and the rate of detection of hyperplastic glands was 44 per cent versus 24 per cent (P = 0.19), respectively. There was no correlation between scan results and size, weight, or location of adenomatous glands. The cost of dual-phase MIBI was comparable to that of ultrasound. Dual-phase MIBI is more sensitive than ultrasound in the localization of adenomas and is the preferable modality for preoperative parathyroid localization. Neither MIBI nor ultrasound is effective in localization of hyperplastic glands, underscoring the importance of routine bilateral neck exploration.

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To evaluate whether a prolonged infusion of Tc-99m sestamibi allows for visualization of viable myocardium in areas of hypoperfused myocardium, 25 patients were prospectively studied. Each patient was imaged four times in two consecutive days in the following manner: day 1:1) immediately after injection of Tl-201 at rest, 2) 1 hour after a bolus injection of Tc-99m sestamibi at rest; and day 2: 1) imaging in the Tl-201 window for 24 hour redistribution, 2) imaging after a 1-hour infusion of Tc-99m sestamibi. The two Tc-99m sestamibi and two Tl-201 studies were evaluated for presence of redistribution. This was present both on the Tl-201 and Tc-99m sestamibi studies (concordant) in 13 cases, and absent on both the Tl-201 and Tc-99m sestamibi studies (concordant) in 9 cases. In two cases redistribution was seen on the Tl-201 images only, and in one case it was seen on the Tc-99m sestamibi images only (discordant). Tc-99m sestamibi infusion may provide information about the presence of viable myocardium which is similar to that provided by Tl-201 24-hour imaging.

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SPECT imaging was utilized in 1052 liver/spleen and 338 brain imaging evaluations. In a quality assurance retrospective analysis with clinical and tissue diagnoses, SPECT liver images had a higher correlation than CT or ultrasound. In brain imaging, SPECT matched MRI in correlation and was more sensitive than CT in evaluating the posterior fossa. SPECT was positive earlier than CT in the discovery of cerebral infarcts. In several cases, primary brain tumors were initially diagnosed on SPECT images. SPECT imaging is a cost effective modality.

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