Current applications of immunoscintigraphy in prostate cancer.

While adenocarcinoma of the prostate has always been one of the top three lethal malignant diseases in adult men, the ever-increasing size of the older male population due to prolonged life expectancy has added to the importance of this condition. It is estimated that over 133,000 new cases of prostatic cancer will be diagnosed this year and some 34,000 men will die from the disease. Thus, the importance of early detection and accurate staging has become more critical, particularly since safe and effective treatments are available. There is still considerable debate as to the most effective means of detection and routine screening procedures for prostatic cancer in men over the age of 50 yr. Digital rectal examination, prostatic-specific antigen determinations and rectal ultrasonography are the most successful and cost-effective screening procedures available. Regardless of the technique used, simple, accurate and reproducible staging is essential. Total surgical removal of the prostate, whether by radical retropubic or perineal approach, along with a lymph node dissection, is a potentially curative procedure. This is true provided the clinical staging is accurate and no undetected metastatic lesions are present. It is in this latter area that current technology is lacking. Routine technetium bone scans are not specific for prostatic cancer. Similarly, abdominal/pelvic computed tomography studies fail to detect lesions in localized prostatic cancer. A tumor-specific scan that detect not only bony lesions but also soft-tissue lesions would be optimal. Some believe that monoclonal antibodies directed at tumor-specific antigens afford this opportunity. We report on the Phase 1 clinical study results using an indium-labeled conjugate of the 7E11-C5.3 murine monoclonal antibody in patients with prostate cancer.

Correlative imaging with monoclonal antibodies in colorectal, ovarian, and prostate cancer.

Monoclonal antibody (MoAb) imaging has contributed greatly to the diagnosis and staging of both colorectal and ovarian cancers, and recently has been tested in patients with prostate cancer. Anatomic imaging modalities such as computed tomography, ultrasound, and magnetic resonance imaging have deficiencies in imaging each of these cancers that can be complemented or overcome by using radioimmunoscintigraphy. The management of patients with colorectal cancer, in particular, has been aided by developments in immunoscintigraphy. The new, safe, and easy-to-prepare MoAbs make possible an effective form of colon and rectal cancer imaging that has been used for (1) staging primary colorectal tumors in presurgical patients, (2) determining extent of disease, (3) continuing surveillance of patients at risk for recurrence of disease, (4) managing patients with elevated carcinoembryonic antigen levels (even those with otherwise negative workup results), and (5) imaging for occult, disease in patients both before and after surgery. In ovarian cancer patients, MoAbs are promising as safe, sensitive imaging tools. The U.S. Food and Drug Administration has approved 111In satumomab pendetide (OncoScint CR/OV; Cytogen Corporation, Princeton, NJ) for use in imaging colorectal and ovarian cancer. Immunoscintigraphy is being refined and tested to locate bony and soft-tissue metastases in patients with prostate cancer. As both a complementary tool and, in some cases, the imaging modality of choice, MoAbs have proven to be safe, accurate imaging tools for many patients with cancer.

Monoclonal antibodies in ovarian and prostate cancer.

Radioimmunoscintigraphy (RIS)--using radiolabeled monoclonal antibodies (MoAbs) to image disease--is a growing subspecialty of nuclear medicine. RIS of the reproductive tracts of men and women has shown encouraging results in imaging both primary lesions and metastases of these cancers. Ovarian cancer is the most fatal gynecologic cancer in the United States, and prostate cancer is the most prevalent form of cancer in men. Several MoAbs against reproductive tumor antigens were used with limited success in clinical trials before 1989. Most recently, MoAbs CYT-103 (satumomab pendetide) and OV-TL 3 have shown promise as safe, sensitive imaging tools for ovarian cancer. Although to date more agents have been used to image ovarian carcinoma than prostate cancer, research has been restimulated in prostate carcinoma imaging because of development of a promising MoAb conjugate, CYT-356. Radionuclide indium-111 appears to be the most promising radiolabeled to date for ovarian and prostate carcinoma RIS performed in the United States. In future clinical trials, consideration of safety issues and a standardization of methods among institutions using RIS are needed before the use of MoAb technology in cancer imaging will become routine. Comparative studies with more traditional methods like computed tomography are needed, as well as more trials comparing radioimmunoscintigraphic findings with pathological evidence.

Quantitative analysis of In-111 satumomab pendetide immunoscintigraphy. An aid to visual interpretation of images in patients with suspected carcinomatosis.

The diagnosis of the diffuse intrapertioneal spread of ovarian or colorectal carcinoma (carcinomatosis) can be difficult when based on visual interpretation of immunoscintigraphic images alone. Twenty-nine patients with either colorectal or ovarian cancer were retrospectively evaluated by three technologists for carcinomatosis employing a quantitative analysis technique that compares uptake of In-111 satumomab pendetide (Oncoscint CR/ OV, Cytogen Corp., Princeton, NJ) in a region of interest in the femoral vascular bundle to the uptake in two regions of interest in the lower abdomen, resulting in an uptake ratio (UR). All 29 patients underwent laparotomy after immunoscintigraphy. Of the 29 patients evaluated, 7 had histologically proven carcinomatosis obtained from the laparotomy. Using quantitative analysis, patients who did not have carcinomatosis had a mean uptake ratio of 1.12, and patients with carcinomatosis had a mean uptake ratio of 2.12. The differences between the means of these two groups of patients was statistically significant for all three technologists (P < .05). The results of this study indicate that there is a significant difference in uptake ratios between patients with carcinomatosis and those without it, and that quantitative analysis can be a useful adjunct to visual interpretation.

In-111 CYT-103 immunoscintigraphy in the imaging of ovarian carcinoma.

Fifteen presurgical patients with a history of ovarian carcinoma were evaluated with immunoscintigraphy using the In-111-labeled monoclonal antibody conjugate CYT-103. Twelve of these patients had residual neoplasia at time of laparotomy. A single intravenous dose of the radiolabeled monoclonal antibody was given to these patients before restaging laparotomy. All patients also underwent CT scanning of the abdomen and pelvis before laparotomy. Immunoscintigraphy detected the presence of disease in 10 of 12 patients before surgery, whereas CT scanning detected disease in only 6 of these 12 women. The results of this study indicate that immunoscintigraphy using In-111 CYT-103 is more sensitive than CT and may add useful information to the preoperative evaluation of women with ovarian carcinoma.

The role of monoclonal antibody in the management of prostate adenocarcinoma.

PURPOSE: A study using monoclonal antibody ProstaScint was conducted to determine the role of radioscintigraphy for evaluation of patients with adenocarcinoma of the prostate. Previous evaluations determining sensitivity and toxicity for this agent were conducted in a multicenter study. MATERIALS AND METHODS: ProstaScint scans were used for preoperative staging in patients presumed to be candidates for total prostatectomy and a subsequent study was performed for the detection and localization of recurrent prostate cancer following definitive therapy. RESULTS: The monoclonal antibody scan detected localized recurrent cancer in 43 patients who were possible candidates for external beam radiation therapy. CONCLUSIONS: The monoclonal antibody conjugate ProstaScint provides additional information in detection and localization of recurrent prostate cancer and would be helpful in the selection of patients for subsequent external beam radiation therapy.

Patient perceptions of pain, paresthesia, and swelling after orthognathic surgery.

The aims of this study were to determine patients' perceptions of pain, paresthesia, and swelling after orthognathic surgery and to analyze the association between these perceptions and neuroticism, temporomandibular joint dysfunction, and mood states among the patients. Levels of pain, paresthesia, and swelling were measured by two self-appraisals that were developed for this research. Perceptions of facial discomfort decreased with time and varied according to the surgical procedure. Patients who scored high on neuroticism tests reported greater levels of temporomandibular joint symptoms before surgery and greater experiences of pain 2 years after surgery. Perceived pain appeared to exert a negative influence on mood states up to 2 years following surgery. These results reveal the importance of continued psychological support for orthognathic surgery patients throughout their course of treatment.

Neurosensory changes following orthognathic surgery.

Much variability exists among studies of neurosensory disturbance following facial surgery. This diversity of findings may be a function of the different surgical procedures and measurement methods used. The present study compared 3 methods of assessing neurosensory loss following surgical orthodontics. Two objective tests and 1 subjective test were administered to 24 patients preoperatively and 4 weeks postoperatively. These included measures of 2-point discrimination, pressure-pain thresholds, and perceived sensation changes in specific facial regions. Postoperatively, all patients needed greater separation on the 2-point discrimination test in the lower facial regions, but not in the upper regions. Bilateral sagittal split osteotomy patients, especially males, required greater separation on these lower sites. Pressure-pain thresholds were not significantly impaired in most patients. Those who underwent combined maxillary and mandibular procedures experienced lower thresholds on the lower lip, while bilateral sagittal split osteotomy patients reported lower thresholds on the upper lip. The 2-point discrimination test was consistent with patients' self-ratings of neurosensory problems using facial maps, but the pressure-pain test was not. The majority of patients reported changed sensation in the lower facial regions postoperatively, regardless of surgery type. Examiners were less likely to rate these same facial regions as different in sensory acuity. Male patients were more likely to report sensory loss or pain postoperatively. These findings suggest that self-reports of neurosensory change following orthognathic surgery are consistent with tests of 2-point discrimination and somewhat higher than examiner ratings, but the objective test of pressure-pain thresholds in this study was least sensitive to neurosensory changes.

Immunoscintigraphy of colorectal carcinoma utilizing 111In-labeled monoclonal antibody conjugate CYT-103.

Twelve presurgical patients with colorectal carcinoma received a single intravenous infusion of 0.5-20.0 mg of the radiolabeled monoclonal antibody conjugate CYT-103. This product is an immunoconjugate of B72.3 labeled with Indium-111 (111In). Patients underwent preoperative gamma camera imaging and computed tomographic (CT) scanning of the abdomen and pelvis. Fifteen intraabdominal sites of tumor were found at surgery. Monoclonal antibody imaging detected 87% of these lesions, whereas CT of the abdomen and pelvis detected 47%. Monoclonal antibody imaging identified tumor in 27% of the patients in which CT did not identify any sites of tumor. The results of this study indicate that monoclonal antibody imaging using [111In]CYT-103 is useful for the preoperative evaluation of colorectal carcinoma patients and the results are complimentary to CT of the abdomen and the pelvis.

Immunoscintigraphy of prostatic cancer: preliminary results with 111In-labeled monoclonal antibody 7E11-C5.3 (CYT-356).

A phase 1 study was conducted with the investigational immunoscintigraphic agent, 111In-CYT-356, a radiolabeled, site-specific immunoconjugate of monoclonal antibody 7E11-C5.3, in 40 patients with prostatic carcinoma and known distant metastases. Each patient received a single intravenous infusion of CYT-356 (dose range, 0.1-5 mg) radiolabeled with approximately 5 mCi of 111In. None of the patients experienced adverse reactions. One patient who received a 5-mg dose developed antibodies to the CYT-356 immunoconjugate. 111In-CYT-356 immunoscintigraphy detected bony metastases in 21 of 38 patients (55%), including 12 of 14 (86%) receiving concomitant hormonal therapy, and soft tissue lesions in four of six patients (67%). Antibody imaging detected occult lesions in the bony pelvis and lumbar spine, which were confirmed by follow-up imaging tests, in one patient. Higher CYT-356 doses may clear the blood pool more slowly. These results suggest that 111In-CYT-356 can be safely administered to patients with prostatic carcinoma and that further clinical investigation of this agent is warranted.

Multicenter radioimmunoscintigraphic evaluation of patients with prostate carcinoma using indium-111 capromab pendetide.

BACKGROUND: Optimum therapy for prostate carcinoma patients requires accurate staging, but computed tomography (CT) and magnetic resonance imaging (MRI) have limitations as methods for detecting soft tissue metastases. In this study, radioimmunoscintigraphy (RIS) was evaluated for its ability to identify sites of metastatic disease in lymph nodes. METHODS: RIS was evaluated in 51 prostate carcinoma patients at high risk for metastatic disease. An intravenous infusion of indium-111 capromab pendetide was given, followed by nuclear medicine imaging on two separate dates. Bilateral, open pelvic lymph node dissection was performed with additional exploration and biopsy of scan positive extraprostatic regions. Histologic evaluation of removed tissue confirmed the accuracy of RIS. In addition, results were compared with other standard methods for diagnosing patients prior to surgery. RESULTS: Nineteen patients (37%) had evidence of lymph node involvement with RIS. Fifteen of the 19 positive patients had pathologic evidence of cancer in the biopsied lymph nodes. Sensitivity, specificity, accuracy, and the positive predictive value for detection of extraprostatic disease were 75%, 86%, 81%, and 79%, respectively. CT, MRI, and ultrasound of the pelvis demonstrated a combined accuracy of only 48% in detecting lymph node disease. Twenty-five previously undetected sites were deemed positive with RIS. Fourteen of these were biopsy-proven tumor sites, seven were probable tumor sites, and four were assumed to be false-positive. CONCLUSIONS: RIS had an impact on patient management through its detection of occult disease in more than 50% of prostate carcinoma patients studied, and it provided information concerning the likelihood that lymph node metastases would be found during surgery.

Immunoscintigraphy with indium-111-capromab pendetide: evaluation before definitive therapy in patients with prostate cancer.

OBJECTIVES: No standard noninvasive diagnostic test reliably differentiates patients with organ-confined prostate cancer from those with lymph node metastases. The ability of a radiolabeled monoclonal antibody, indium-111 (111ln)-capromab pendetide, to identify sites of metastatic disease in patients at moderate to high risk of nodal involvement was investigated. METHODS: The study prospectively evaluated 160 patients with prostate cancer scheduled to undergo pelvic lymph node dissection (PLND) before or during definitive treatment. All were at relatively high risk of nodal involvement by virtue of significantly elevated baseline prostate-specific antigen (PSA) values, Gleason scores, and/or locally advanced clinical stages of disease. The histologic findings of the PLNDs were compared with the results of immunoscintigraphy, computed tomography, and magnetic resonance imaging. RESULTS: Among the 152 evaluable patientS studied with 111In-capromab pendetide before PLND, the sensitivity of immunoscintigraphy for lymph node detection was 62% and the specificity was 72%; the positive predictive value was 62% and the negative predictive value was 72%. In comparison, the sensitivity of computed tomography and magnetic resonance imaging was 4% and 15%, respectively, and the specificity was 100% for both procedures on the basis of a large number of negative interpretations. Logistic regression analysis revealed that immunoscintigraphy with 111In-capromab pendetide provided strong, independent evidence of the presence of lymph node metastases. Furthermore, the analysis indicated that certain combinations of PSA, Gleason score, and 111In-capromab pendetide were particularly effective at predicting the risk of nodal involvement. CONCLUSIONS: Immunoscintigraphy with 111In-capromab pendetide outperformed standard diagnostic imaging techniques in the detection of prostate cancer lymph node metastases and provided independent prognostic information that complemented PSA, Gleason score, and clinical stage.