Hani Abdel-Nabi

Radiolabeled antibody imaging in the management of colorectal cancer. Results of a multicenter clinical study.

Presurgical colorectal cancer patients (n = 116) received single intravenous infusions of 1 mg of CYT-103 (OncoScint CR103), an immunoconjugate of monoclonal antibody B72.3, radiolabeled with 111In. Following gamma camera imaging, 103 patients underwent an operative procedure: 92 had primary or recurrent colorectal carcinoma, 1 patient evaluated for recurrence of colorectal cancer had a second primary malignancy (small cell lung), and 10 patients had no demonstrable evidence of malignancy. 111In-CYT-103 immunoscintigraphic findings were consistent with the pathologic diagnoses for 70% of patients with colorectal cancer and 90% of disease-free patients. Antibody imaging contributed to surgical decision making through the detection of occult disease (12% of patients) and the confirmation of localized, potentially resectable disease without regional or metastatic spread. Seven patients (6%) experienced adverse effects, primarily fevers and itching, and 33% of patients developed antibodies to murine immunoglobulin after administration of 111In-CYT-103. The results of this study suggest that 111In-CYT-103 is a useful diagnostic tool for the presurgical evaluation of colorectal cancer patients.

Current status of cancer immunodetection with radiolabeled human monoclonal antibodies

The use of radiolabeled murine monoclonal antibodies (MoAbs) for cancer immunodetection has been limited by the development of human antimouse antibodies (HAMA). Human monoclonal antibodies do not elicit a significant human antihuman (HAHA) response. The generation and production of human monoclonal antibodies met with technical difficulties that resulted in delaying their clinical testing. Human monoclonal antibodies of all isotypes have been obtained. Most were immunoglobulin (Ig) M directed against intracellular antigens. Two antibodies, 16.88 (IgM) and 88BV59 (IgG3k), recognize different epitopes on a tumor-associated antigen, CTA 16.88, homologous to cytokeratins 8, 18, and 19. CTA 16.88 is expressed by most epithelial-derived tumors including carcinomas of the colon, pancreas, breast, ovary, and lung. The in vivo targeting by these antibodies is related to their localization in nonnecrotic areas of tumors. Repeated administration of 16.88 over 5 weeks to a cumulative dose of 1,000 mg did not elicit a HAHA response. Two of 53 patients developed a low titer of HAHA 1 to 3 months after a single administration of 88BV59. Planar imaging of colorectal cancer with Iodine-131 (131I)-16.88 was positive in two studies in 9 of 12 and 16 of 20 patients preselected by immunohistochemistry. Tumors less than 2 cm in diameter are usually not detected. The lack of immunogenicity and long tumor residence time (average = 17 days) makes 16.88 a good candidate for therapy. Radioimmunlymphoscintigraphy with indium-111 (111In)-LiLo-16.88 administered by an intramammary route was used in the presurgical staging of primary breast cancer. The negative predictive value of lymph node metastases for tumors less than 3 cm was 90.5%. Planar and single photon emission computed tomography imaging of colorectal carcinoma with technetium-99m (99mTc) 88BV59 was compared with computed tomography (CT) scan in 36 surgical patients. The antibody scan was more sensitive than the CT scan in detecting abdominal and pelvic tumors: 68% versus 40% (P < .05). The combination of antibody scan and CT scan was superior to CT scan alone: 80% versus 40% (P < .01). Lesions as small as 0.5 cm in diameter were detected by antibody scan. The CT scan appears superior to the antibody scan for liver metastases. Patients with a high serum titer of HAMA from previous exposure to murine antibodies were successfully imaged. Antibody scans obtained with 99mTc-88BV59 have imaging characteristics similar to murine antibody scans obtained with radiolabeled IgGs. The absence or weak immunogenicity of the human monoclonal antibodies makes them good candidates for radioimmunodetection and radioimmunotherapy.

Clinical applications of indium-111-labeled monoclonal antibody imaging in colorectal cancer patients.

During the past two decades, the in vivo application of monoclonal antibodies (MoAbs) in cancer diagnosis and therapy have been widely studied. This can be related to three main factors: (1) dramatic improvement in monoclonal antibody production, revolutionized by Kohler and Milstein; (2) improvement in radioisotopes and monoclonal antibody conjugation procedure and further simplification and ease of use of these procedures; and (3) the apparent safety of single or, in selected cases, multiple administration of MoAbs to humans. The development of radioimmunoscintigraphy or radioimmunodetection has added a significant new dimension to nuclear imaging, and it is very likely to broaden our approach to diagnosis and perhaps therapy of malignant diseases. The indications and limitation of radioimmunoscintigraphy must be clearly outlined to the referring oncologists and surgeons. The unique capability of radiolabeled MoAbs in detecting occult disease, upstaging patients, and, most importantly, changing patient management must be emphasized.

In‐111 CYT‐103 monoclonal antibody imaging in patients with suspected recurrent colorectal cancer

Recurrent colorectal cancer is seen in as many as 40% of patients after curative resection. In view of the limitations of endoscopic and cross‐sectional imaging, external immunoscintigraphy has been added to the follow‐up regimen of patients at high‐risk of recurrent disease. The authors investigated the utility of immunoscintigraphy with Indium‐111 (In‐111) CYT‐103 (site specifically labeled conjugate of monoclonal antibody B72.3) in 19 patients with suspected recurrences after previous curative resection of colorectal carcinoma. Local or regional recurrences (4 patients) and liver metastasis (6 patients) were indicated by physical examination and computed tomography (CT), whereas nine patients had occult disease with increasing serum carcinoembryonic antigen (CEA) levels and negative conventional workups. Serum CEA levels were elevated (mean, 22 ng/ml) in all patients. Approximately 4.3 mCi In‐111 labeled to 1.0 mg CYT‐103 was administered intravenously to each patient. Planar and single photon emission computed tomography (SPECT) imaging were performed 2–5 days after infusion. The final diagnosis of recurrence or metastasis was established in 18 patients by second‐look surgery or biopsy. One patient died before exploration. Tumor was identified at the following locations: pelvis (12 patients), abdominal wall (2 patients), retroperitoneum (1 patient), liver (5 patients), and omentum (2 patients). Superiority of monoclonal antibody (MoAb) scan is noted in the detection of pelvic and intraabdominal recurrences (100%) versus CT scan (43%). Liver metastases were identified with equal facility by both modalities. In‐111 CYT‐103 scan findings influenced the management of 10 (55%) of 18 patients. Surgery was avoided in one patient with disseminated metastases detected by the scan. Correct identification of occult local recurrences was made in six patients. An isolated liver metastasis was confirmed in one patient with equivocal CT scan. Finally, additional intraabdominal lesions were detected in two patients. These results suggest an important and beneficial role for In‐111 CYT‐103 MoAb imaging in patients with suspected recurrent colorectal carcinomas, particularly in patients in whom cross‐sectional imaging is negative; such imaging may prevent patients from undergoing unnecessary surgical exploration.

Carcinoembryonic antigen immunoscintigraphy complements mammography in the diagnosis of breast carcinoma

An adjunctive noninvasive test that is predictable and highly specific for breast carcinoma would complement the high false‐positive rate of mammography in certain patients.

Immunoscintigraphy with111 In-satumomab pendetide in patients with colorectal adenocarcinoma: Performance and impact on clinical management

PURPOSE: The role of immunoscintigraphy with111 Insatumomab pendetide in the medical and/or surgical management of colorectal cancer patients was evaluated in a multicenter trial. METHODS: This 103 patient study population included 46 individuals with rising serum carcinoembryonic antigen levels and otherwise negative diagnostic evaluation, 29 patients with known recurrence, presumed to be isolated and resectable, and 28 patients for whom standard diagnostic tests provided equivocal information. RESULTS: No adverse reactions were noted following intravenous administration of 1 mg of satumomab pendetide radiolabeled with approximately 5 mCi of111 In. Thirty percent of patients developed human anti-mouse antibodies postinfusion. In the 84 patients for whom correlation with histopathologic, diagnostic, and/or clinical findings was available, antibody imaging demonstrated a sensitivity of 73 percent in patients with confirmed tumor (36/49) and negative results for all 35 patients with no evidence of malignancy. Occult disease was detected in 18 patients. CONCLUSION: 111 In-satumomab pendetide immunoscintigraphy was helpful in the medical and/or surgical management of 45 (44 percent) patients and provided information unavailable from other diagnostic modalities.

Results of immunoscintigraphy using a cocktail of radiolabeled monoclonal antibodies in the detection of colorectal cancer

AbstractBackground: External immunoscintigraphy using a single monoclonal antibody has been employed successfully to localize primary, recurrent, and occult colorectal carcinoma. This prospective study investigated the accuracy and sensitivity of external immunoscintigraphy when the combination or “cocktail” of radiolabeled monoclonal antibodies, CYT-103 (an IgG1a) and CYT-372 (an IgG2b) directed against TAG-72 and CEA, respectively, is given to patients with known or suspected colorectal cancer. Methods: Eleven patients enrolled in this open label phase I/II study underwent preoperative external immunoscintigraphy after intravenous cocktail administration of two indium 111-labeled monoclonal antibodies (MoAb), CYT103 and CYT372. Antibody dose ranged from 0.2 mg (five patients) to 1.0 mg (six patients), each antibody radiolabeled with 2.5 mCi of indium 111, delivering a total dose of 5 mCi per patient. Planar and SPECT images were performed 2 to 5 days postinjection. Suspected lesions were surgically resected within 2 weeks of injection. Results: A total of 23 lesions (sites) were identified in the eleven patients, 19 of which were confirmed by pathology (hematoxylin and eosin [H&E]). Cocktail immunoscintigrams identified 16 of the 19 confirmed lesions. Computed tomography (CT) scan detected 9 of the 19 lesions. The sensitivities of cocktail immunoscintigraphy and CT scan for the detection of colorectal cancer were 84% and 64%, respectively. The positive predictive value for immunoscintigraphy was 94%. The antibody scans detected six occult, previously unsuspected lesions. Cocktail immunoscintigraphy changed the surgical management in four of the 11 (36%) patients. Conclusions: The combination of In 111 CYT-103 and CYT-372 improved the sensitivity of external immunoscintigraphy for the detection of colorectal cancer compared to that obtained with a single MoAb imaging. Cocktail antibody imaging may enhance the staging and management of patients with cancers of colon and rectum.

Iodine-131 labeled anti-CEA antibodies uptake by Hürthle cell carcinoma.

Localization of Hürthle cell cancer deposits in the lung with l-131 labeled anti-carcinoembryonic antigen (CEA) monoclonal antibody is described. This technique may prove useful if conventional scanning with l-131 sodium iodide for distant metastases is negative.

Nonvisualization of sterile surgical incisions with indium-111 labeled leukocytes.

The localization of ln-111 labeled leukocytes (WBCs) in recent surgical incisions was studied in 18 patients, ln-111 WBC images correlated well with culture results and clinical findings. No accumulation of ln-111 WBCs was detected at the site of noninfected incisions in nine patients, ln-111 WBCs did accumulate at incision sites in nine patients with infected surgical incisions. These results indicate that ln-111 WBC study can accurately distinguish between normal healing and infection of recent surgical incisions.