Radioimmunodetection of medullary thyroid cancer using a bispecific anti-CEA/anti-indium-DTPA antibody and an indium-111-labeled DTPA dimer

Two-step radioimmunotargeting using a bispecific anti-CEA/anti-in-DTPA monoclonal antibody and an 111In-labeled DTPA dimer (diDTPA-TL) was evaluated nine times in eight patients with medullary thyroid cancer (MTC). Immunoscintigraphy was performed 5 and 24 hr after injection of 111In-diDTPA-TL. For five patients, radioimmunoguided surgery (RIGS) was performed using a hand-held gamma probe (sodium iodine), and a biodistribution study was performed 48 hr (four times) and 24 hr (one time) after injection of 111In-diDTPA-TL. Mean tumor uptake (%ID/kg in tumor) was 39 (range 2.75-139). In these five patients, immunoscintigraphy visualized all known tumors and detected unknown foci (US and CT were negative) in the neck (once) and neck and liver (once). Immunoscintigraphy, performed four times in search of a recurrence, detected unknown localizations in the mediastinum and neck (twice) and was negative twice. There were no false-positives. In three of five patients who had surgery, RIGS localized tumor foci not detected by the surgeon. RIGS failed to detect two small lesions (10 x 10 mm) corresponding to sites of fibrosis and microscopic cancer infiltration. Bispecific anti-CEA/anti-In-DTPA mediated targeting of 111In-diDTPA-TL provided elevated tumor uptake and tumor-to-normal tissue ratios. Radioimmunodetection of small MTC lesions is thus possible even when morphological imaging techniques prove negative.     

Bispecific monoclonal antibody-mediated targeting of an indium-111-labeled DTPA dimer to primary colorectal tumors: pharmacokinetics, biodistribution, scintigraphy and immune response

Eleven patients with primary colorectal carcinoma tumors (4 +/- 2 cm) were given intravenous injections of 1-10 mg of an anti-CEA, anti-In-DTPA bispecific Fab'-Fab monoclonal antibody, and 2-8 days later, were injected with 1.2-4.2 nmol of an 111In-labeled DTPA dimer (6 mCi). The bispecific antibody exhibited good stability and F(ab)'2-like pharmacokinetics. After injection, the 111In-DTPA dimer distributed in a large volume (88 ml/kg-180 ml/kg) and cleared through the kidneys (mean residence time in the whole body: 9 hr-16 hr). Uptake of 111In by the tumor using this two-step technique (1.8%-17.5% injected dose ID/kg, measured from surgical samples 48 hr after hapten injection) was not found significantly lower than that achieved with our reference 111In-labeled anti-CEA F(ab)'2 1 to 4 days after injection in six patients with similar clinical status (5.5%-30.2% ID/kg). In addition, tumor-to-blood and tumor-to-liver uptake ratios were significantly improved (blood 7.8 versus 4.2, liver 2.8 versus 0.8). As a result, low background images allowed detection of 12 of 13 lesions, 4 hr and 24 hr after hapten injection. However, 7 of 11 patients developed HAMA.     

Clinical and immune responses in advanced colorectal cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen

Carcinoembryonic antigen (CEA) is expressed in a wide variety of adenocarcinomas, and it is well recognized that cancer patients are immunologically "tolerant" to CEA. The purpose of this study was to determine whether we could break immune tolerance to CEA by vaccinating patients with a monoclonal anti-idiotype antibody that is the internal image of CEA and to determine what impact this might have on patient survival. Twenty-four patients with advanced CEA-positive colorectal cancer who failed standard therapies except for two were entered into this Phase Ib trial. One patient was considered not assessable, because on the day of entering into the study, she was diagnosed with acute myelogenous leukemia. Patients were treated with 1, 2, or 4 mg of aluminum hydroxide-precipitated 3H1 anti-idiotype antibody every other week for four injections and then monthly until tumor progression was observed. Immunological monitoring included humoral and cellular idiotypic and CEA responses, and all patients were evaluated for toxicity, response, and survival. Hyperimmune sera from 17 of 23 patients demonstrated an anti-anti-idiotypic Ab3 response, and 13 of these responses were demonstrated to be true anti-CEA responses (Ab1'). The antibody response was polyclonal, and 11 mediated antibody-dependent cellular cytotoxicity. Ten patients had idiotypic T-cell responses, and five had specific T-cell responses to CEA. None of the patients had objective clinical responses, but overall median survival for the 23 evaluable patients was 11.3 months, with 44% 1-year survival (95% confidence interval, 23-64%). Toxicity was limited to local swelling and minimal pain. Anti-idiotype monoclonal antibody 3H1 that mimics CEA was able to break immune tolerance in the majority of treated patients. Overall survival of 11.3 months was comparable to other phase II data with advanced colorectal cancer patients treated with a variety of chemotherapy agents, including irinotecan, with considerably less toxicity. Although it is not clear that the vaccine itself had an impact on survival, this should be determined in a Phase III randomized trial.     

Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: phase I trial results

PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine 131 (131I)-labeled 81C6 monoclonal antibody (mAb) in brain tumor patients with surgically created resection cavities (SCRCs) and to identify any objective responses to this treatment. METHODS: In this phase I trial, eligible patients were treated with a single injection of 131I-labeled 81C6. Cohorts of three to six patients were treated with escalating dosages of 131I (starting dose of 20 mCi with a 20-mCi escalation in subsequent cohorts) administered through an Ommaya reservoir in the SCRC. Patients were followed up for toxicity and response until death or for a minimum of 1 year after treatment. The SCRC patients, who were previously irradiated, were followed up without additional treatment unless progressive disease was identified. RESULTS: We administered 36 treatments of 131I doses up to 120 mCi to 34 previously irradiated patients with recurrent or metastatic brain tumors. Dose-limiting toxicity was reached at 120 mCi and was limited to neurologic or hematologic toxicity. None of the patients treated with less than 120 mCi developed significant neurologic toxicity; one patient developed major hematologic toxicity (MHT). The estimated median survival for patients with glioblastoma multiforme (GBM) and for all patients was 56 and 60 weeks, respectively. CONCLUSION: The MTD for administration of 131I-labeled 81C6 into the SCRCs of previously irradiated patients with recurrent primary or metastatic brain tumors was 100 mCi. The dose-limiting toxicity was neurologic toxicity. We are encouraged by the minimal toxicity and survival in this phase I trial. Radiolabeled mAbs may improve the current therapy for brain tumor patients.     

Carcinoembryonic antigen (CEA) assays in obstructive colorectal cancer

Four of 40 patients with resectable colon or rectal cancer had tumors causing acute large bowel obstruction with colonic dilatation; all 4 patients had preoperative CEA titers above 10 ng/ml with a mean of 28 ng/ml. Thirty-six cancer patients without acute colon obstruction had a mean CEA titer of 4.5 ng/ml; only 6 of 36 patients had circulating CEA titers 10 ng/ml or greater. This suggested that pre-treatment CEA titers in patients with obstructing cancer are unusually high. Multiple CEA assays were performed on two of the 4 patients with colonic obstruction before and after bowel decompressive procedures and prior to their definitive treatment. Relief of obstruction alone produces marked reduction in circulating CEA; this suggested that not only the extent of disease but also the pathophysiological changes associated with obstruction influenced circulating CEA levels.     

Novel clinical approaches in monoclonal antibody-based management in colorectal cancer patients: radioimmunoguided surgery and antigen augmentation

In animals, changes in brain temperature induce a shift in frequencies in the electroencephalogram (EEG). Given the large decreases in body and brain temperature that occur during hibernation, putative functions that were previously ascribed to certain EEG frequencies are no longer valid because of the progressive shift away from the original frequency. In the present review it is proposed that even moderate temperature changes in humans and animals, such as those across the circadian or menstrual cycle, or induced by drugs, have a significant effect on EEG frequencies and the corresponding power spectrum. Alterations in the relative EEG power spectrum, in studies where body temperature also changes, may not be a direct cause of the treatment under investigation, but a consequence of effects on body or brain temperature. However, these effects on the EEG power spectrum are usually interpreted to result directly from the experimental treatment.     

Dose escalation of cyclophosphamide in patients with breast cancer: consequences for pharmacokinetics and metabolism

PURPOSE: The alkylating anticancer agent cyclophosphamide (CP) is a prodrug that undergoes a complex metabolism in humans producing both active and inactive metabolites. In parallel, unchanged CP is excreted via the kidneys. The aim of this study was to investigate the influence of dose escalation on CP pharmacokinetics and relative contribution of activating and inactivating elimination pathways. PATIENTS AND METHODS: Pharmacokinetics of CP were assessed in 12 patients with high-risk primary breast cancer who received an adjuvant chemotherapy regimen that included four courses of conventional-dose CP (500 mg/m2 over 1 hour every 3 weeks) followed by one final course of high-dose CP (100 mg/kg over 1 hour). Plasma concentrations of CP were analyzed by high-performance liquid chromatography (HPLC), 24-hour urinary concentrations of CP, and its inactive metabolites (carboxyphosphamide, dechloroethylcyclophosphamide [dechlorethylCP], ketocyclophosphamide [ketoCP]) were determined by 31-phosphorus-nuclear magnetic resonance (31P-NMR)-spectroscopy. RESULTS: There was no difference in dose-corrected area under the concentration-time curve (AUC) (216 v 223 [mumol.h/[mL.g]), elimination half-life (4.8 v 4.8 hours), systemic clearance (79 v 77 mL/min) and volume of distribution (0.49 v 0.45 L/kg) of CP between conventional- and high-dose therapy, respectively. However, during high-dose chemotherapy, we observed a significant increase in the renal clearance of CP (15 v 23 mL/min; P < .01) and in the formation clearance of carboxyphosphamide (7 v 12 mL/min; P < .05) and dechloroethylCP (3.2 v 4.2 mL/min; P < .05), whereas metabolic clearance to ketoCP remained unchanged (1.3 v 1.2 mL/min). Consequently, metabolic clearance to the remaining (reactive) metabolites decreased from 52 to 38 mL/min (P < .001). The relative contribution of the different elimination pathways to overall clearance of CP demonstrated wide interindividual variability. CONCLUSION: Overall pharmacokinetics of CP are apparently not affected during eightfold dose escalation. However, there is a shift in the relative contribution of different clearances to systemic CP clearance in favor of inactivating elimination pathways, thereby indicating saturation of bioactivating enzymes during dose escalation. Besides individual enzyme capacity, hydration and concomitant medication with dexamethasone modulated CP disposition.     

A phase I clinical trial of murine monoclonal antibody D612 in patients with metastatic gastrointestinal cancer

In a phase I study, 21 patients with metastatic adenocarcinoma of the gastrointestinal tract received the murine monoclonal antibody D612. This antibody is directed at a M(r) 48,000 antigen restrictively expressed on tumors of the gastrointestinal tract and to a limited degree on normal gastrointestinal mucosa. Patients received total doses of 10-180 mg/m2 administered as single or multiple doses of 1-100 mg/m2 over an 8-day period. Dose-limiting toxicity was secretory diarrhea. A single dose of 100 mg/m2 exceeded guidelines for maximal tolerated dose. Higher total doses were achieved in subsequent patients by using repeated administration of lower doses. Three of five patients receiving 60 mg/m2 for 3 doses (180 mg/m2 total dose) experienced grade 3 diarrhea and could not complete the prescribed course. The dose of 40 mg/m2 administered on days 1, 4, and 8 (total dose, 120 mg/m2) has been selected as the dose for phase II studies. The pharmacokinetics of D612 is best described by a one-compartment model with a mean t1/2 of 48 +/- 3 h (SEM). Eighteen of 21 patients developed human anti-mouse antibody (HAMA). Patients who developed high levels of HAMA demonstrated a more rapid clearance of the day 8 dose than those who developed low levels of HAMA. In all patients studied, a component of HAMA was directed at the D612 variable region. With one exception, serum from all patients with detectable antibody to the D612 variable region demonstrated anti-paratope reactivity. Thirty-four % of known metastatic sites demonstrated uptake of radiolabeled D612. There were no objective antitumor responses in this phase I trial. The antitumor effect of D612 in vitro has been shown to be potentiated by interleukin 2 and recombinant human macrophage colony-stimulating factor. A phase II study of D612 administered in combination with cytokines that enhance human effector function is presently ongoing.     

Phase I/II trial of combined 131I anti-CEA monoclonal antibody and hyperthermia in patients with advanced colorectal adenocarcinoma

BACKGROUND: This pilot project was undertaken to evaluate the toxicity of and tumor response to combined 131I anti-carcinoembryonic antigen monoclonal antibody (131I anti-CEA RMoAb) and hyperthermia in patients with metastatic colorectal adenocarcinoma. METHODS: Nine patients who had colorectal carcinoma with liver metastases were enrolled in this study. Intact 131I anti-CEA RMoAb was used (the specific antibody was IMMU-4, provided by Immunomedics, Inc., Morris Plains, NJ). During the diagnostic phase, dosimetry revealed that the tumor site received a higher radiation dose than the surrounding normal tissues in only six patients. These six, who were treated with radioimmunotherapy and hyperthermia, were the basis of this study. The first three patients were treated with 30 mCi/m2 of 131I anti-CEA RMoAb, and the next three received 60 mCi/m2. Pharmacokinetic clearance data were reported for all nine patients. RESULTS: Thermometry data revealed an average T90 of 40.3 (+/- 1.4 degrees C) and T50 of 41.1 (+/- 1.2 degrees C). The average thermal dose equivalent at 42.5 degrees C was 34.5 (+/- 21.5) minutes. The average Tmin, Tmax, and Tmeam were 40 (+/- 1.2 degrees C), 42.4 (+/- 0.7 degrees C), and 41.1 (+/- 1.1 degrees C), respectively. The pharmacokinetic clearance data of antibody showed monoexponential plasma clearances in all patients except one, in whom a biexponential plasma clearance was observed. In general, similar plasma and whole-body clearances as well as similar urinary excretions were observed when diagnostic and therapeutic phases for each patient were compared. Two of the six patients showed a marked improvement in their symptoms; five patients showed a drop in carcinoembryonic antigen levels. A follow-up computed tomography scan one month after treatment showed no change in tumor volume in five patients; one patient showed a partial response. Three patients developed toxicity, two developed moderate thrombocytopenia (39,000 and 58,000), and the other patient developed hematoma resulting from the insertion of a catheter for thermometry. CONCLUSIONS: It is feasible to combine hyperthermia and radiolabeled monoclonal antibodies, and the combination was well tolerated by these patients. The interaction between hyperthermia and low dose rate radioimmunotherapy is complex. Further studies are necessary to explore the use of this combined modality in the management of maligancies.     

Phase II study of dual 131I-labeled monoclonal antibody therapy with interferon in patients with metastatic colorectal cancer

The combination of COL-1 (anti-CEA) and CC49 (anti-TAG-72) has shown an increase in binding and distribution in colon cancer by immunoperoxidase staining compared to either antibody alone. To overcome tumor heterogeneity and allow delivery of higher radiation dose, 131I-labeled COL-1 and CC49 at a total dose of 75 mCi/m2 (2775 MBq/m2) were simultaneously administered to 14 patients with metastatic colon cancer. alpha-IFN (3 x 10(6) IU) was given s.c. on days -5 to +3 to increase carcinoembryonic antigen and TAG-72 antigen expression. Most patients had mild symptoms during IFN therapy, including mild neutropenia, fever, and malaise, which rapidly subsided after IFN cessation. No acute allergic reactions occurred with radioimmunotherapy; two patients experienced transient, delayed grade 2 arthralgias. Transient neutropenia and/or thrombocytopenia, which was maximal at 4-6 weeks, were consistent side effects without adverse events. All patients had tumor localization, and 13 of 14 patients achieved 4+ (highest grade) localization readings to at least one known site of disease. No objective responses occurred; 4 patients were stable and 10 progressed. Tumor dose estimates varied from 393 to 1327 cGy, including liver and extrahepatic sites. Combining two complementary antibodies and IFN administration appeared to increase localization intensity and radiation doses at tumor sites as compared to historical controls. The amount of radiation delivered to tumor sites was still below that required to cause tumor regressions in metastatic colorectal cancer.     

False-positive imaging of In-111 labeled monoclonal antibody conjugate CYT-103 in a patient with metastatic colorectal carcinoma

In-111 satumomab whole-body imaging is used in the evaluation of patients with colorectal carcinoma. The authors report a case of false-positive In-111 localization in a nonfunctional adrenal adenoma in a patient with metastatic colon carcinoma.     

Carcinoembryonic antigen (CEA) monitoring of radiation therapy for colorectal cancer

Serial CEA radioimmunoassays were performed on 16 patients receiving preoperative radiation therapy of rectal cancer or irradiation of recurrent or metastatic colorectal cancer. Radiation therapy of localized colorectal cancer reliably reduced previously elevated circulating CEA titers. Significant decrease of elevated CEA titers with accumulating doses of irradiation may indicate that the bulk of CEA-producing tumor is within the radiation treatment portal and assist in patient management decisions. The decrease of circulating CEA with preoperative radiation therapy was of short duration and may indicate that surgical resection should not be delayed more than 6-8 weeks after irradiation. Because of the high frequency of false positive and false negative results, CEA must be used only in conjunction with other clinical and laboratory parameters.     

Biodistribution of (111)indium-labeled engineered human antibody CTMO1 in ovarian cancer patients: influence of protein dose

Thirty-one patients suspected of having ovarian cancer received a single i.v. injection of radiolabeled (100 MBq (111)In) engineered human CTMO1 (hCTMO1) to investigate its potential as an internalizing drug carrier. hCTMO1 is a complementary-determining region-grafted human IgG4 monoclonal antibody recognizing an ovarian carcinoma-associated antigen, the MUC-1-gene product. The amount of radioactivity was determined in tumor tissue, various normal tissues, including liver biopsies, and blood samples obtained at laparotomy, 6 days after injection of either 0.1 or 1.0 mg hCTMO1/kg of body weight. Circulating antigen-15-3 was measurable in all patients before injection, and immune complex formation was already present at the end of infusion. In the 0.1 mg/kg group, most of the radioactivity was bound to immune complexes, whereas in the 1.0 mg/kg group, most was bound to IgG monomers. Increasing the hCTMO1 dose 10-fold did not influence the overall disappearance of (111)In from the blood, but the elimination half-life of (111)indium bound to immune complexes was increased 2-fold. Uptake in tumor tissue 6 days postinjection at the 0.1 mg/kg dose was 7.6 times higher (P = 0.0009) than in normal tissue and 2.5 times higher (P = 0.03) than in blood. At the 1.0 mg/kg dose, the uptake in tumor tissue was 14.0 times higher (P = 0.0003) than in normal tissue and 8.1 times higher (P = 0.0007) than in blood. Liver activity was substantial (23.7 +/- 10.5 and 18.3 +/- 6.7% of the injected dose/kg for the 0.1 and 1.0 mg/kg dose group, respectively). These results are superior to those found with other clinically tested anti-MUC-1 gene product antibodies. hCTMO1 seems to be a suitable carrier for cytotoxic agents in ovarian carcinoma patients; the better uptake results and tumor-to-blood ratios are obtained at the higher dose of 1.0 mg hCTMO1/kg body weight.     

Establishment of anti-idiotype monoclonal antibodies to human anti lung cancer monoclonal antibody (4G12)

The object of this study is to establish anti-idiotype (anti-ID) monoclonal antibodies (MoAbs) against a human MoAb (4G12) that highly reacts with lung squamous cell carcinomas. Two murine anti-ID MoAbs (2H1 and 2B12) were established by hybridoma technology. They showed specific reactivity with 4G12 but not with 3H12 human MoAb, human IgM and human IgG. These two MoAbs demonstrated more than 90% of binding inhibition of 4G12 to lung squamous cell cancer cell line (PC10). Moreover, cross inhibition test showed that 2H1 and 2B12 detect different idiotypes of 4G12 each other. Furthermore, specific reactivity of anti 2H1 and anti 2B12 sera to PC10 were observed by cell binding ELISA. These two anti-ID MoAbs had internal image of the original antigen.     

Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration

In this study the potential of intraperitoneal (i.p.) and intravenous (i.v.) administration of chimeric iodine-131-labelled MOv18 IgG for radioimmunotherapy was determined. The dosimetry associated with both routes of administration of cMOv18 IgG was studied in patients. Eight patients suspected of having ovarian carcinoma received 150 MBq 131I-cMOv18 IgG i.p. Blood and urine were collected and serial gamma camera images were acquired. Another group of four patients received 7.5 MBq 131I-cMOv18 IgG i.v. For all patients, tissue biopsies were obtained at surgery. Activity in the blood after i.p. administration was described by a bi-exponential curve with a mean uptake and elimination half-life of 6.9+/-3.2 h and 160+/-45 h, respectively. For i.v. infusion the mean half-life for the elimination phase was 103+/-12 h. Cumulative excretion in the urine was 17%+/-3% ID and 21%+/-7% ID in 96 h for i.p. and i.v. administration, respectively. Scintigraphic images after i.p. administration showed accumulation in ovarian cancer lesions, while all other tissues showed decreasing activity with time. Tumour uptake determined in the ovarian cancer tissue specimens ranged from 3.4% to 12.3% ID/kg for i.p. administration and from 3.6% to 5.4% ID/kg for i.v. administration. Dosimetric analysis of the data indicated that 1.7-4.3 mGy/MBq and 1.7-2.2 mGy/MBq can be guided to solid or ascites cells after i.p. and i.v. administration, respectively. Assuming that an absorbed dose to the bone marrow of 2 Gy will be dose limiting, a total activity of 4.1 GBq 131I-cMOv18 IgG can be administered safely via the i.p. route and 3.5 GBq via the i.v. route. At this maximal tolerated dose, a maximum absorbed dose to 1-g tumours in the peritoneal cavity of 18 and 8 Gy can be reached after i.p. and i.v. administration, respectively. For the i. p. route of administration, dose estimates for the tumour are even higher when the electron dose of the peritoneal activity is also taken into account: total doses to the tumour of 30 Gy and 22 Gy will be absorbed at the tumour surface and at 0.2 mm depth, respectively. In conclusion, therapeutic tumour doses can be achieved with 131I-cMOv18 IgG in patients with intraperitoneal ovarian cancer lesions with no normal organ toxicity. The i.p. route of administration seems to be preferable to i.v. administration.     

Phase II trial of edatrexate in patients with metastatic colorectal cancer

Edatrexate is an analog of methotrexate which in vitro demonstrated activity against human colon cancer xenografts grown in nude mice. In a phase II trial, 12 patients with metastatic colorectal cancer and no prior chemotherapy were treated with Edatrexate 80 mg/m2/week for an initial period of 8 weeks. No objective responses were observed. Edatrexate is inactive against colon cancer at the dose and schedule used in this trial.     

Biodistribution of radiolabeled monoclonal antibody E48 IgG and F(ab'')2 in patients with head and neck cancer

The amphibian pronephros is fated to die during early development. Pronephric cells undergo apoptosis and their function is replaced by the mesonephros, which becomes the functional kidney of the adult frog. Tadpoles of the northern leopard frog, Rana pipiens, were inoculated with a Lucké tumour herpesvirus (LTV) preparation. Most of the animals developed typical Lucké renal carcinomas at metamorphosis. Fewer developed carcinomas of the pronephric cell type. A pronephric carcinoma, rescued from apoptosis by the herpesvirus, was harvested from a post-metamorphic frog. The tumour was judged to be pronephric by its anatomical location (in the anterior part of the body) and because both mesonephric kidneys were intact and tumour-free upon removal of the tumour mass. A tumour fragment was fixed for histological examination, which confirmed that the tissue was a renal carcinoma. A further fragment was subjected to short-term culture in order to produce metaphase cells for cytogenetical analysis. Based upon silverstained nucleolar organizing region numbers, 14 of 15 metaphase cells were estimated to have the diploid number (2N = 26) of chromosomes and a karyotype was constructed which did not appear to differ from that of normal cells. A single cell was estimated to be tetraploid (4N = 52). This is the first report of chromosomes of a pronephric Lucké carcinoma. LTV replicates only in tumour tissue maintained in the cold. Because the frog in this study had been maintained in the laboratory at 22 degrees C for about 10 months, no viruses would have been detectable with electron microscopy. However, the presence of Lucké herpesvirus DNA was detected in tumour homogenates by polymerase chain reaction amplification of a 1.2 kbp Hind III restriction fragment of the LTV DNA. The presence of LTV DNA provided assurance that the rescued pronephric tumour was indeed a Lucké carcinoma.     

Phase II evaluation of topotecan in patients with advanced colorectal cancer. A Southwest Oncology Group trial (SWOG 9241)

By using the indirect immunofluorescence assay and the tissue cells infected with coxackie virus Group B as antigen, the authors detected the antibodies type IgM to coxsackie virus Group B (CVB-IgM) of the sera of 105 children with viral myocarditis (VMC), 59 children with other diseases (COD) and 67 healthy children (HC). The results showed that in VMC, the genometric mean titre (GMT) of CVB-IgM in female (1:16.58) was higher than that in male (1:9.28, P < 0.05); not only in female, but also in male the GMT of VMC was higher than that of HC; also the GMT in female of VMC was higher than the GMT in female of COD, but no considerable difference existed between male of VMC and COD. Without sex distinction the GMT of HC was 0.289, its standard variance was 0.9335, the upper limit titre of normal range was 1:8.6. The authors took 1:10 as the positive criterion, the sensitivity of CVB-IgM in diagnosing VMC was 79.05%, the specialities of differentiating VMC from COD and HC were 42.3% and 91.04%, the consistancy rates of diagnosing VMC from COD and HC were 65.85% and 83.72% respectively.     

Monitoring cancer antigen 125 in serum of ovarian cancer patients after administration of 131I-labeled F(ab')2 fragments of OC125 antibody

We evaluated the effect of repeated administration of OC125 F(ab')2 fragments on cancer antigen (CA) 125 determination in 210 serum samples from 30 patients. We found falsely high CA 125 concentrations in 142 (68%) samples, using a homologous CA 125 enzyme immunoassay (EIA) with OC125 antibodies. The Truquant OV2 method, which involves two other murine antibodies, and the IMx CA 125 method, which uses sheep antibodies as capture antibodies, resulted in only slightly increased (false-positive) values in some samples with exceptionally high CA 125 EIA values. We measured falsely low CA 125 values in 37 (18%) samples with the Truquant OV2 method. Interferences could be eliminated by removal of serum IgG. Our results suggest that interferences are to some extent caused by anti-idiotypic IgG induced by OC125 administration. Assays involving nonmurine anti-CA 125 antibodies as capture antibodies seem to be most suited for CA 125 determination after OC125 treatment, but in every case an apparent increase of CA 125 after OC125 infusion should be validated.