Diagnosis of breast carcinoma with radiolabeled monoclonal antibodies (MoAbs) to carcinoembryonic antigen (CEA) and human milk fat globulin (HMFG).

The current study attempted to assess the potential proficiency of radioimmunodetection (RAID) of primary, residual, multicentric, and recurrent breast carcinoma using two radiolabeled murine monoclonal antibodies (MoAbs), anti-human milk fat globulin (HMFG1) labeled with iodine (123I) and anti-carcinoembryonic antigen (CEA) labeled with technetium (99Tc). Thirteen patients with suspicious clinical and/or mammographic primary or recurrent breast carcinoma were studied in a phase I-II prospective, consecutive, nonrandomized, noncontrolled study. Five patients received intravenous infusion with 0.5-2.0 mg anti-CEA MoAb type CYT 380 labeled with 99Tc [13-22 millicurie (mCI)] and 8 patients received intravenous infusion with 0.25-1.0 mg anti-HMFG1 MoAb (Unipath, U.K.) labeled with 123I (4-17 mCI). Both MoAbs used in this study demonstrated ability to bind specifically to breast cancer lesions, resulting in successful RAID in 10 of 12 of studied patients (5 of 5 patients in the anti-CEA-99Tc and 5 of 7 in the anti-HMFG-123I group--accuracy 83.3%). One patient was excluded due to protocol violation. Seven patients had true-positive scans when correlated with surgery (sensitivity 87.5%). The MoAb scans accurately diagnosed lesions in 3 of the 4 primary invasive breast carcinomas confirmed histologically. Presence of residual carcinoma following wide excision was established in 1 of 2 patients and presence of soft tissue metastases in 3 patients. Three patients had true-negative scan (specificity 75%): 2 patients presented with suspicious mammographic recurrence postlumpectomy and 1 patient had questionable soft tissue recurrence. One patient with primary breast carcinoma had a false-negative scan and another had a false-positive scan in the presence of fibrosis following lumpectomy and radiation therapy. No adverse reactions were noted in the patients studied. RAID findings were confirmed by immunohistochemistry in 6 of 9 cases studied. Our data suggest that radiolabeled MoAbs used in this study are potentially useful diagnostic agents for evaluation of primary or recurrent breast carcinoma, particularly in the areas where conventional methodology is limited.

Scintigraphic detection of gastric and pancreatic carcinomas with In-111 ZCE 025 monoclonal antibody.

We have evaluated the role of In-111 anti-CEA (carcinoembryonic antigen) monoclonal antibody ZCE 025 in 8 patients. Three patients had a confirmed diagnosis of gastric carcinoma. Three had a confirmed diagnosis of pancreatic carcinoma. Two patients had elevated serum levels of CEA with no known primary. Each patient received 5.5 mCi In-111 ZCE 025 infused at doses of 10-80 mg. Planar and single photon emission computed tomography (SPECT) imaging at 3 and 7 days after infusion detected 9 of 12 known tumor sites and all 5 of the previously identified sites of metastasis. In-111 ZCE 025 MoAb imaging also found 6 previously unsuspected tumor sites and changed the preoperative evaluation in 50% of the patients studied. It changed the clinical management in 2 patients and established the site of primary involvement in 2 others. There were no clinical or biochemical reactions. In-111 ZCE 025 monoclonal antibody scintigraphy is a useful adjunct in the evaluation of patients with either gastric or pancreatic carcinoma. It may have a beneficial impact on the surgical decision making in these patients.

Clinical experience with intra lymphatic administration of 111In-labelled monoclonal antibody PAY 276 for the detection of pelvic nodal metastases in prostatic carcinoma.

The ability of 111In-PAY 276 (anti prostatic acid phosphatase antibody) in detecting pelvic lymph node metastasis following bipedal intra lymphatic administration was studied in five patients with carcinoma of the prostate. The labeled antibody was injected directly into the lymphatics of each foot. Planar and tomographic images radioactivity content of lymph nodes resected during staging pelvic lymphadenectomy were compared to the histologic and immunoperoxidase findings. Radioactivity in pelvic lymph nodes was prominently seen within 20 min of injection and was present 16 days later. Persistent accumulation of tracer in the lymphatics of the lower extremities was also observed in all patients 16 days post injection. Radioactivity counts in tumor-free lymph nodes were higher than in tumored lymph nodes resected. Our results demonstrate that intra lymphatic administration of 111In-labeled PAY 276 monoclonal antibody has major technical limitations, and that further research directed at the causes of tracer accumulation in the lymphatics and tumor-free lymph nodes is required.

Colorectal tumors: scintigraphy with In-111 anti-CEA monoclonal antibody and correlation with surgical, histopathologic, and immunohistochemical findings.

A prospective clinical study of 17 patients with a histologic diagnosis of colorectal carcinoma proved at colonoscopy and surgery was performed with indium-111 anticarcinoembryonic-antigen (CEA) monoclonal antibody (MoAb), ZCE-025. MoAb scanning depicted nine of 16 primary colorectal carcinomas on planar scintigrams (true-positive findings = 56%) and ten of 16 lesions on single-photon emission computed tomography (SPECT) scans (true-positive findings = 62%). Liver metastases were detected in three of three patients, and lymph node metastases were detected in one of four patients. Immunohistochemical examination for CEA in resected colorectal cancer tissues demonstrated a positive correlation between MoAb imaging of primary lesions and cytoplasmic-stromal intracellular CEA distribution. There was no correlation between CEA serum levels and lesion detectability with MoAb scanning.

Morphology and glycoprotein synthesis of uterine glandular epithelium in human basal plate at term: an ultrastructural and autoradiographic study.

This study describes the morphologic features of uterine glandular epithelium in human basal plate at term and identifies this epithelium as an active site of glycoprotein synthesis. Wedge biopsies were obtained from the basal plate at the time of repeat cesarean section from 11 normal pregnant patients at term. Biopsy specimens were either processed immediately for microscopic examination or incubated in vitro with 25 microCi/cc of 3H-galactose or 3H-leucine. Tissues incubated with tritiated compounds (2-hour pulse +/- 3-hour chase in nonradioactive medium) were either processed for light microscopic autoradiographic analysis or extracted for determination of trichloroacetic-acid-precipitable tritiated macromolecules in tissues and medium. Profiles of cuboidal-columnar glandular epithelium were identified in the decidual component of the basal plate region adjacent to spiral arterioles and perpendicular to the inner layers of myometrial muscle. Autoradiographic and biochemical studies identified the glandular epithelium, as well as large decidual cells, to be major sites of incorporation of both 3H-galactose and 3H-leucine and to be prime sources for secretion of tritiated macromolecules that appeared in the medium during in vitro incubation of basal plate tissue. Ultrastructurally, the glandular epithelium was noted to rest on a basal lamina, to have lateral cell membranes with numerous desmosomes, and to exhibit an apical surface with microvilli projecting into a luminal space. Cytologic features of the cells included abundant profiles of rough endoplasmic reticulum, multiple mitochondria with lamellar cristae, a well-developed perinuclear but nonpolarized Golgi apparatus,and nuclei containing predominantly euchromatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Differentiation and secretory activities of cultured human placental cytotrophoblast.

Ultrastructural, autoradiographic, immunofluorescent and biochemical techniques were used to characterize primary cultures of term placental cytotrophoblast in order to gain insight into the differentiation and secretory capacities of the cellular component of human trophoblast. Trypsin treatment of placental villi allowed isolation of a predominantly cytotrophoblast cell population that maintained viability up to 13 weeks in monolayer culture. Autoradiographic studies of tritiated thymidine incorporation identified a smaller diameter mononucleated cell population that was mitotically active and developed into larger diameter mononucleated cells and into multinucleated cells during culture. Ultrastructurally, cultured cells formed desmosomes, had an extensive network of cytoplasmic microfilaments and contained the organelles for hormone synthesis and secretion. These cells secreted steroid hormones, secreted Schwangerschafts protein I, actively incorporated tritiated glycoprotein precursors and expressed surface immunoreactivity for the beta-subunit of human chorionic gonadotrophin (hCG). However, medium concentrations of hCG and human placental lactogen dropped rapidly to undetectable levels after 14 days in primary culture. Cells grown beyond confluence differentiated into 1 to 2 mm structures with a villus-like histology. Our studies indicate that cytotrophoblast can secrete steroids, cytotrophoblast differentiation occurs in vitro in the absence of maternal tissues, hCG synthesis occurs in cultured cytotrophoblast and medium concentrations of placental protein hormones are not the best indicators of cell viability for cultures of cytotrophoblast.