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PubMed1980

Clinical studies on the radioimmunodetection of tumors containing alpha-fetoprotein.

This study reports the use of radiolabeled antibodies to alpha-fetoprotein for the detection and localization of hepatocellular and germ cell carcinomas. Twelve patients with histories of histologically-confirmed neoplasia received a total dose between 1.0 and 4.4 mCi of 131I-labeled goat IgG prepared against human alpha-fetoprotein. Total-body photoscans were taken with a gamma scintillation camera at various intervals after injection of the radioactive antibody. Computer subtraction of radioactive technetium background images from the antibody 131I scans permitted the visualization of all tumor sites known to be present in 4 patients with either primary hepatocellular cancer or metastatic germ cell carcinoma of the testis. In contrast to the results with the specific antibody, radioactive normal goat IgG given to one of these patients with metastatic embryonal carcinoma of the testis failed to show equivalent localization. Among 8 patients with diverse neoplasms not believed to contain alpha-fetoprotein, 5 of 19 tumor sites showed radioactive antibody accretion, although significantly less than in the patients with liver or testicular cancer. Circulating antigen levels of up to 15,000 ng per milliliter did not prevent successful tumor imaging after intravenous injection of the radioantibody. This investigation indicates that alpha-fetoprotein-containing tumors can be detected and localized in vivo by the method of radioimmunodetection.

Adult↗
PubMed1986

Radioimmunodetection of human colon carcinoma xenografts in visceral organs of congenitally athymic mice.

The LS-174T human colon carcinoma line and A375 human melanoma line were used to establish primary tumor xenografts at three sites (subcutaneous, spleen, and kidney) in congenitally athymic mice. A monoclonal antibody (MAb) reactive with the LS-174T line, B72.3 IgG, was labeled with iodine 125, and an isotype-identical control antibody MOPC-21, was labeled with iodine 131. Labeled antibodies were injected intravenously in tumor-bearing mice, and animals were killed at varying intervals. Tumor-to-blood and tumor-to-organ ratios of MAb 72.3 indicated no significant difference at any of the three primary tumor sites in LS-174T tumor-bearing mice. The percent injected dose per gram was higher at visceral sites on day 3, but was similar on days 5 and 7 at all sites. Localization indices on all days ranged from 4 to 1 to greater than 16 to 1, confirming the specificity of the B72.3 reactivity at all sites. Athymic mice bearing tumor xenografts were scanned on day 7, and the LS-174T spleen and kidney tumors were imaged, with efficacy similar to that of the subcutaneous site. The visceral tumor model is more representative of the human disease, and may therefore be a better model for evaluation of monoclonal antibodies for radioimmunodetection and therapy for cancer in intra-abdominal organs.

Animals↗
PubMed1989

Radioimmunodetection of lymph node invasion in prostatic cancer. The use of iodine 123 (123I)-labeled monoclonal anti-prostatic acid phosphatase (PAP) 227 A F(ab')2 antibody fragments in vivo.

The therapeutic indications in prostatic cancer depend on the regional and distant extension of the cancer and are difficult to assess before lymphadenectomy. Radioimmunodetection of lymph node involvement with monoclonal anti-prostatic acid phosphatase (PAP) antibodies can be proposed as a noninvasive alternative to lymphadenectomy. Fifteen patients with various stages of histologically proven prostatic cancer were examined by immunolymphoscintigraphy (ILS) before treatment to detect lymph node metastases. These patients had Stage A (n = 7), Stage B (n = 3), Stage C (n = 2), and Stage D (n = 3) tumors. They received between 100 and 400 micrograms of monoclonal antibody 227 A in the form of F(ab')2 fragments labeled with iodine 123 (123I). The antibody was injected directly into the periprostatic area. ILS images were obtained after 1, 3, 6, and 24 hours. Three days later, each patient underwent a lymphadenectomy for histologic examination. The results of the histologic examination and ILS were compared. In ten patients, the examination did not show any images capable of being interpreted as lymphadenopathy and histologic examination confirmed the integrity of the nodes examined. In five cases, scintigraphy suggested the presence of lymph node invasion by prostatic cancer and this was confirmed by histologic examination in three of the five cases. Overall, in terms of lymphadenopathy, this examination had a sensitivity of 100% and a specificity of 83%. Therefore, ILS appears to be capable of detecting lymph node metastases in prostatic cancer.

Acid Phosphatase↗
PubMed1985

Radioimmunodetection of murine mammary adenocarcinoma (TA3/Ha) lung and liver metastases with radioiodinated PNA.

Organ-specific lung and liver metastatic variants of the murine TA3/Ha mammary adenocarcinoma cell line were selected by sequential in vivo growth with intervening in vitro cell culture. These variants readily formed specific lung or liver metastatic lesions upon i.v. injection into A/J mice. TA3/Ha cells produce a large cell surface glycoprotein called epiglycanin, which contains a high proportion of Thomsen-Friedenreich (TF) antigenic structures. The presence of non-cryptic TF has been associated with malignancy in humans and animals. We used peanut lectin agglutinin (PNA), which has a preferential affinity for TF antigenic structures, to determine whether these selected metastatic variants retained the TF antigen expression. In vitro, the TA3/Ha metastatic variant lines exhibited strong PNA binding similar to that seen with human RBC after neuraminidase treatment to expose the cryptic TF antigen. In contrast, the non-epiglycanin-producing TA3/St subline did not bind PNA appreciably. Autoradiography of liver sections with TA3/Ha metastatic lesions after 125I-PNA i.v. indicated an avid uptake throughout the viable tumor mass and FITC-PNA staining of these tissue sections readily identified the metastatic tumors under fluorescence microscopy. Tissue biodistribution studies revealed that lung or liver containing the TA3/Ha metastatic variant nodules retained about 7 to 8 times as much of an i.v. dose of radioiodinated PNA as did controls, allowing for clear delineation of tumor-infiltrated lung or liver by gamma scintigraphy. These in vitro and in vivo tests confirm that the selected organ-specific TA3/Ha variants retained the binding characteristics of the parent TA3/Ha line. These observations illustrate the potential utility of radiolabelled PNA for the detection of TF-antigen-expressing tumors and metastases. This murine system with organ-specific TA3/Ha metastatic variants also provides a model for evaluation of various other macromolecular probes for tumor radioimmunodetection of metastatic lesions.

Adenocarcinoma↗
PubMed1987

Antibody protein dose and radioimmunodetection of GW-39 human colon tumor xenografts.

This study investigates the influence of antibody protein dose on the radioimmunodetection of a CEA-producing, human colonic tumor xenograft (GW-39) using affinity-purified goat anti-carcinoembryonic antigen (CEA) antibody and a murine monoclonal anti-CEA antibody (NP-2). Hamsters bearing GW-39 tumors were given an equal mixture of 131I-labelled antibody and 125I-labelled irrelevant IgG at doses varying from 0.01 to 1.0 mg (0.1 to 10 mg/kg body weight) for each antibody preparation. No differences were found in the percentage of antibody in the tumor or the clearance rate from the blood as the antibody dose was increased. The concentration of antibody in the tumor increased proportionally with the antibody dose and maintained a linear relationship with increasing dose, indicating that antigenic sites in the tumor were not saturated with antibody. The concentration of irrelevant IgG in the tumor also increased proportionally as the dose was increased, but the concentration of irrelevant IgG in the tumor was less than the antibody and was removed more rapidly from the tumor than the antibody. By considering the amount of irrelevant IgG in the tumor as a measure of the amount of antibody non-specifically bound, we determined that there was no change in the amount of antibody in the tumor between days 3 and 7, and the amount of antibody increased uniformly for both the tumor and non-tumor tissues, resulting in no improvement in the tumor/non-tumor ratios with increasing antibody dose. External scintigraphy verified that the dose of the antibody did not influence tumor imaging. Thus, tumor accretion of antibody in this model is not dependent principally on the antibody protein dose, and other factors such as accessibility to antigen and antibody metabolism may play important roles in regulating the uptake of antibody in tumor.

Animals↗
PubMed1988

Radioimmunodetection of human pancreatic tumor xenografts using DU-PAN II monoclonal antibody.

The potential of DU-PAN II, monoclonal antibody (IgM), which was raised against the human tumor cell line, was evaluated for radioimmunodetection of human pancreatic tumors (PAN-5-JCK and EXP-58) grown in nude mice. 125I-labeled DU-PAN II was accumulated into PAN-5-JCK producing DU-PAN II antigen with a tumor-to-blood ratio of 2.72 +/- 3.00, but it did not localize in EXP-58 because of insufficient DU-PAN II. There was no significant uptake of 125I-nonimmunized IgM in PAN-5-JCK. These facts indicated the specific tumor uptake of DU-PAN II. Excellent images of the tumor PAN-5-JCK were obtained 3 days after the injection of 125I-DU-PAN II. Gel chromatography was also investigated with respect to the plasma taken from mice injected with antibody, or incubated with antibody in vitro. The results indicate that circulating antigen affected the tumor uptake of DU-PAN II: The more the tumor grew, the higher the amount of antigen excreted into the blood, leading to the degradation of DU-PAN II before it reached the tumor sites. Consequently, the immunoscintigram of the small tumor was remarkably clear. The catabolism and the radiolysis of the labeled IgM injected are critical points in applying immunoscintigraphy.

Animals↗
PubMed1988

Anti-fibrin monoclonal antibodies for radioimmunodetection: preliminary assessment in a rat model system.

The D Dimer (DD) site formed by linkage of D domains from adjacent fibrin (FN) molecules is unique to cross-linked FN and its degradation products and is not found in FN monomer or fibrinogen (FB). Thus monoclonal antibodies (MAb) reactive to DD should have a very suitable specificity for in vivo thrombus detection. Two anti-DD MAbs have been labelled with 131-I and assessed as scintigraphic agents in a normal rat model system. Each rat received 3 sc implants of antigen covalently coupled to Sepharose beads: 1) Human DD 2) Human FB 3) Glycine (GL) (control). Scintigraphic images taken 7 days after injection of 131-I anti DD MAb showed clear localisation of both anti-DD MAbs to the DD implant rather than to the FB or GL implants with no localisation in normal tissues. This was confirmed in biodistribution studies. Injection of anti-DD MAbs DD-3B6/22 and DD-IC3/108 resulted in DD: blood ratios of 10.4 +/- 0.6 and 4.9 +/- 0.3 respectively. These results suggest that anti-DD MAbs will have potential for thrombus radioimmunodetection.

Animals↗
PubMed1990

Radioimmunodetection of uterine leiomyosarcoma with 111In-labeled monoclonal antimyosin antibody Fab fragments.

Radioimmunodetection of uterine leiomyosarcoma in a 64-year-old woman with a palpable local recurrence is described. Pathological abdominal, pelvic, and thoracic accumulation of monoclonal 111In-labeled antimyosin was observed. Afterward, these lesions were examined by whole-body X-ray computed tomography. With a double-tracer technique (pulmonary and hepatic/splenic subtractions) the lesions were delineated better and SPECT (radioisotope tomography) was used for more accurate localization of the abdominal and pelvic lesions. These findings indicate that antimyosin scintigraphy might be useful in staging and follow-up of uterine leiomyosarcoma.

Antibodies, Monoclonal↗
PubMed1986

Radioimmunodetection of cutaneous T-cell lymphoma with 111In-labeled T101 monoclonal antibody.

T101 monoclonal antibody recognizes a pan-T-cell antigen present on normal T cells and also found in high concentrations in cutaneous T-cell lymphoma. We used this antibody, radiolabeled with 111In, in gamma-camera imaging to detect sites of metastatic cutaneous T-cell lymphoma in 11 patients with advanced disease. In all patients, [111In]T101 concentrated in pathologically or clinically detected nodes, including those in several previously unsuspected nodal regions. Concentrations (per gram of tissue) ranged from 0.01 to 0.03 percent of the injected dose and were consistently 10 to 100 times higher than previously reported on radioimmunodetection. Focal uptake was seen in skin tumors and heavily infiltrated erythroderma but not in skin plaques. The specificity of tumor targeting was documented by control studies with [111In]chloride or [111In]9.2.27 (anti-melanoma) monoclonal antibody. Increasing the T101 dose (1 to 50 mg) altered distribution in nontumor tissues. These studies suggest that imaging with [111In]T101 may be of value in identifying sites of cutaneous T-cell lymphoma. In contrast to the targeting of solid tumors, the mechanism of localization appears to be related to binding to T cells, which can then carry the radioactivity to involved sites.

Adult↗
PubMed1981

Human chorionic gonadotropin radioantibodies in the radioimmunodetection of cancer and for disclosure of occult metastases.

Radioimmunodetection (RaID) of tumors containing human chorionic gonadotropin (hCG; choriogonadotropin) was evaluated in 25 patients by injecting 131I-labeled goat antibody IgG against hCG and performing total-body photoscans with a gamma scintillation camera 24 and 48 hr later. All 10 testicular cancer patients with proven tumor sites had positive RaID results, whereas three cases without known tumor were negative. Four patients with hydatidiform mole and one with degenerative products of conception showed positive RaID results consistent with elevated serum hCG titers. Two putatively false-positive results were obtained in patients with lung or ovarian cancer, whereas a false-negative metastasis to the liver of a patient with lung cancer and an elevated serum hCG titer was observed. Of 14 tumor sites found by RaID in 10 testicular cancer patients, 4 were revealed by RaID prior to any other detection method used and provided a lead time to definitive diagnosis by other measures of a few days to greater than 1 yr. Although a number of patients had high serum hCG levels, even exceeding 3 microgram/ml, the xenogeneic antibody was capable of localizing in tumor. No adverse effects were noted in any of the patients studied. Thus, hCG RaID appears to be a safe and effective method of detecting and locating hCG-producing tumors and has been found to disclose occult testicular cancers.

Adenocarcinoma↗
PubMed1999

Preoperative clinical radioimmunodetection of pancreatic cancer by 111 In-labeled chimeric monoclonal antibody Nd2.

The present study was carried out with the purpose of evaluating the clinical usefulness of radioimmunodetection (RAID) with 111In-labeled murine/human chimeric monoclonal antibody, Nd2 (c-Nd2) in patients with pancreatic cancer. Nineteen patients suspected to have pancreatic cancer were administered intravenously 74 MBq/2 mg 111In-labeled c-Nd2 in 100 ml of saline containing 2% albumin over 30 min. A scintigram was obtained on the 3rd day after infusion by using single photon emission computed tomography (SPECT) imaging. Of the 14 patients finally diagnosed as having pancreatic cancer on the basis of surgical specimens or progress of disease, specific focal uptake at the site of the tumor was detected in 12 (true positive cases), representing a sensitivity of 85.7% (12/14), and liver metastasis was found in one case with metastasis. Of the 5 patients diagnosed with tumor-forming pancreatitis (TFP), 4 patients demonstrated true negative imaging, but one patient whose tumor demonstrated interesting findings in histology and immunostaining, showed false positive imaging. Of patients investigated for human anti-chimeric antibody (HACA) response, none showed HACA response, and no allergic reaction was seen in any of the patients administered c-Nd2. These results suggest that RAID with 11In-labeled c-Nd2 is useful for differential preoperative diagnosis between invasive pancreatic cancer and TFP.

Aged↗
PubMed1983

Radioimmunodetection of cancer using antibodies to alpha-fetoprotein and carcinoembryonic antigen.

This study reports the use of radiolabeled antibody to AFP and CEA for the detection and localization of AFP- or CEA-producing tumors. Thirty-one patients received 131I-labeled anti-AFP or anti-CEA antibodies. Photoscans were taken at 24 and 48 hours after injection of radioantibodies. In three of six patients with CEA-producing tumors, radioimmunodetection with anti-CEA antibody showed positive scans. In AFP-producing tumors, 7 of 15 patients had positive findings on immunoscintigraphy using polyclonal anti-AFP antibody, and two of nine patients had positive findings when monoclonal antibodies were used. Analysis of radioantibody in the blood after injection showed both complex and free antibody with immunoreactivity in the circulation, and smaller complexes were seen to form after administration of monoclonal antibodies.

Abdomen↗
PubMed1987

Radioimmunodetection and radioimmunotherapy of cutaneous T cell lymphomas using an 131I-labeled monoclonal antibody: an Illinois Cancer Council Study.

A radiolabeled murine monoclonal antibody (T101) was used for imaging and therapy of six patients with cutaneous T cell lymphoma (CTCL). Radioimmunodetection was performed with a 5.6 to 13.1 mCi 131I-T101 preparation (9.6 to 10.5 mg). A therapeutic dose of 100.5 to 150.1 mCi 131I on 9.9 to 16.9 mg of antibody was administered to five patients, with subsequent retreatment following plasmapheresis in three patients at the time of disease progression. All patients responded to their initial therapy and two patients responded to retreatment. Regression of skin lesions and peripheral adenopathy was witnessed. All patients reported resolution of their chronic pruritus. The duration of response ranged from 3 weeks to 3 months. Acute toxicity included fevers, pruritus, and mild dyspnea in two instances. Myelosuppression was seen in patients receiving the 144.7 mCi, 145.0 mCi, and 150.1 mCi 131I-T101 doses. Radioimmunodiagnostic and therapy studies included gamma scintigraphy, plasma, urinary, and wholebody antibody clearances, and biodistribution determined from skin, bone marrow, and liver biopsies. Immunologic studies included immunoperoxidase staining of target tissues, immunofluorescent flow cytometric analysis on peripheral blood and bone marrow, assays for serum blocking factors, determination of a human antimouse antibody (HAMA) response, and quantitation of circulating T101 levels. These preliminary data suggest that 131I-T101 has therapeutic potential in CTCL and that myelosuppression will be the limiting toxicity.

Aged↗
PubMed1986

Clinical evaluation of anti-alpha-fetoprotein radioimmunodetection.

Anti-alpha-fetoprotein (AFP) radioimmunodetection was performed in response to clinical requests in 16 patients. In two patients, assessment of a known tumour was required; the anti-AFP scans were accurate and provided useful clinical information in both cases. In the remaining 14 patients the request was for localisation of suspected recurrent tumour. Accurate information was provided in four of these patients. In this latter group, various conventional methods of investigation had failed to disclose the site of recurrence. However, of a total of 21 sites reported as positive in these 14 patients, eight proved to be false positives. Two false negative results also occurred in this group and nine could not be evaluated. Although occasionally patients were usefully scanned, improvements are necessary before consistently reliable information can be obtained using this technique.

Abdominal Neoplasms↗
PubMed1991

Radioimmunodetection of degranulated human eosinophils in mice: a potential model for imaging Hodgkin's disease and other pathologic conditions.

Various human tumors such as lymphomas and carcinomas sometimes contain extensive infiltration by degranulating eosinophils. To determine if degranulated eosinophils are suitable targets for immunolocalization, we performed in vivo distribution and imaging studies in mice, using EOS (a murine monoclonal antibody directed to human eosinophil peroxidase) labeled with indium-111. Adult mice were injected intravenously with radiolabeled EOS antibody or with similarly radiolabeled normal mouse IgG before receiving an intramuscular injection into the right thigh of homogenized human eosinophils adsorbed to latex microspheres. There was striking localization in the right thigh of the radiolabeled EOS antibody detectable by gamma imaging techniques as soon as 24 hr after injection. By contrast, there was little accumulation of radiolabeled normal IgG in the right thigh. We conclude that human eosinophil peroxidase is potentially a suitable target for radioimmunodetection and therapy of neoplasms and pathologic conditions that contain degranulating eosinophils.

Animals↗
PubMed1990

Clinical studies of cancer radioimmunodetection with carcinoembryonic antigen monoclonal antibody fragments labeled with 123I or 99mTc.

Seventy-three patients with diverse cancers containing carcinoembryonic antigen received 123I-labeled anti-carcinoembryonic antigen monoclonal antibody F(ab')2 fragment [38 patients], 99mTc-labeled anti-carcinoembryonic antigen monoclonal antibody Fab' fragment [23 patients], or both reagents at different times [6 patients] for evaluation of antibody targeting and imaging [radioimmunodetection (RAID)], using planar and single-photon emission computed tomography. The results indicated that antibody fragments are preferred for early tumor imaging (within 24 h). Rapid targeting and clearance from blood and normal organs of the antibody fragments (blood median t1/2 elimination of 26.5 and 13.2 h for the F(ab')2 and Fab' fragments respectively) permitted the use of short-lived radionuclides, such as 123I (13.3 h) and 99mTc (6 h), and confirmed that selective antibody accretion in tumors occurred very soon after administration, such as between 2 and 5 h. Scan interpretations at 24 h for the 123I-labeled F(ab')2 and at 2-5 h for the 99mTc-labeled Fab' revealed overall sensitivities, on a tumor site basis, of 95.9 and 94.9%, respectively. On a site basis, the overall accuracies were 94.2 and 93.8% for the 123I and 99mTc immunoconjugates, respectively. In the 6 patients studied with both radioimmunoconjugates, a high concordance in detection was found. Both imaging agents also revealed a high number of putatively new tumor sites not disclosed by other radiological methods at the time of the RAID studies, of which 40.0 and 20.5% were subsequently confirmed as tumor for the 123I and 99mTc agents, respectively, within an 11-month follow-up period. This represented 24 proven occult tumor sites in 19 patients given the 123I-immunoconjugate and 16 proven occult tumor sites in 9 patients receiving the 99mTc agent. The new lesions were found up to 17 and 7 months earlier for 123I-RAID and 99mTc-RAID, respectively, than with other detection methods. The smallest tumors identified were below 0.5 cm, especially with the 99mTc immunoconjugate and single-photon emission computed tomography imaging. The findings of this study confirm previous evidence that RAID is a safe and a potentially useful new method of cancer detection. Despite the excellent results with the 123I-F(ab')2 antibody fragment, its poor availability and high cost limit its clinical use. Therefore, the 99mTc agent, which is made by an instant, 1-step, 1-vial, direct labeling method, appears to be the method of choice for rapid and accurate detection of cancer by RAID.

Adolescent↗
PubMed1990

Evidence for interaction of human anti-idiotypic antibodies with CA 125 determination in a patient after radioimmunodetection.

Very high concentrations of CA 125 have been found in some ovarian cancer patients after repeated radioimmunodetection with anti-CA 125 antibodies [OC125-F(ab')2]. In one patient we measured a CA 125 concentration of 135,000 kilo-arb. units/L, using an enzyme immunoassay involving OC125 antibodies. With an immunoradiometric assay involving use of two new anti-CA 125 antibodies (B43.13 and B27.1), the CA 125 concentration was 34 kilo-arb. units/L, indicating a discrepancy. The component responsible for the high result in the enzyme immunoassay could be purified by immunoaffinity chromatography on Protein A-Sepharose. Furthermore this component bound to anti-human IgG-Sepharose in the same manner as did the serum IgG fraction. Adsorption of human anti-mouse antibodies present in the serum did not decrease the CA-125-like material. Binding of whole OC125 antibodies to the purified CA-125-like material was inhibited completely in the presence of CA 125 antigen. We infer that the false-positive CA 125 activity is ascribable to a human IgG directed against an idiotope of the OC125 antibody, which was induced by repeated application of OC125 antibodies. To avoid falsely positive results in patients receiving OC125 antibodies, CA 125 should be measured by an assay in which other antibodies are used.

Aged↗
PubMed1990

Experimental studies of radioimmunodetection of cancer: an overview.

During the past 8 years numerous patients have been treated by injection of radiolabeled monoclonal antibodies for both diagnosis and treatment of cancer. It has become common to refer to this approach by such terms as "antibody guided delivery" or "antibody guided targeting." In general the results, while somewhat promising, have failed to fulfill our initial expectations. It is now clear that there are many physiological barriers that antibodies face in their travel toward their tumor associated antigen. The papers in the "Experimental Studies of Radioimmunodetection" section of the symposium describe in detail these barriers. We must remember that antibody conjugates are no more "guided" than classical drugs and hormones and are subject to the same physiological principals.

Antibodies, Monoclonal↗