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 andlor 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 ¹²³ I (4-17mCI). 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 (sensitiviv 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-negutive 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 immuno-histochemistry 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.     

Radioimmunoscintigraphy in Patients with Ovarian Cancer

The targeting potential of three different monoclonal antibodies (MAbs) was assessed in patients with ovarian cancer. HMFG1, OC-125 and H17E2 labelled with ¹¹¹In or ¹²³I were evaluated prospectively for their ability to localize ovarian tumour. Forty two patients with ovarian cancer, aged 40-78 years (median=58 years) were studied using OC-125 (n=9), HMFG1 (n=11) and H17E2 (n=22). Imaging data were compared with the CT and the surgical findings. Presence of tumour was confirmed in 35/42 (83%) patients (8/9 OC-125, 10/11 HMFG1 and 17/22 H17E2) and correlated well with the conventional radiology diagnostic methods. One patient with a negative H17E2 scan and a large abdominal mass detected at laparotomy revealed a PLAP-negative tumour on immunohistochemistry. Scintigraphy revealed the presence of active disease, confirmed by laparotomy/laparoscopy in 6/8 patients considered to be in clinical remission. The sensitivity of the method was high enough and the diagnostic contribution of this approach should be further evaluated.     

A prospective study of 123I-labeled monoclonal antibody imaging in ovarian cancer

Thirty patients presenting with a pelvic mass were entered into a prospective study on the use of radioimmunoscintigraphy with the 123I-labeled monoclonal antibody HMFG2. The imaging data was obtained without knowledge of the clinical data and compared with subsequent surgical findings. A false-positive diagnosis of ovarian cancer was made in five of ten patients subsequently shown not to have ovarian cancer; thus the technique cannot be used as a screening test. A true-positive diagnosis was made in 19 out of 20 patients shown subsequently to have ovarian cancer. In 18 of these patients the distribution of uptake closely fitted the surgical findings. Methods of improving these results are described. In conclusion, radioimmunoscintigraphy is of no use in determining whether a pelvic mass is due to ovarian cancer, but has benefit in the evaluation of chemotherapy and may, in the future, prevent the need for second-look operations in some circumstances.     

A new immunoassay using monoclonal antibodies HMFG1 and HMFG2 together with an existing marker CA125 for the serological detection and management of epithelial ovarian cancer

A new method with a low pH step to dissociate serum complexes has been developed to measure serum levels of antigens associated with ovarian cancer. The antigens are detected by monoclonal antibodies HMFG1 and HMFG2 and have been compared to an existing ovarian cancer associated antigen detected by the antibody CA125. Elevated HMFG1 was found in 56%, and elevated HMFG2 in 65% of 924 sera from 85 patients with ovarian cancer. CA125 was elevated in 85% of these sera. When the three markers were used in conjunction, 95% of sera from patients with ovarian cancer were positive--compared with 7% in sera from healthy control subjects. Therefore, the combination of HMFG1, HMFG2 and CA125 increases the diagnostic accuracy. If all three markers are normal in a patient previously treated for ovarian cancer then no further positive information regarding disease status can be obtained by ultrasound and CT scanning.     

Impact of Radioimmunoscintigraphy on the Management of Colorectal and Ovarian Cancer Patients: A Retrospective Study

Noninvasive differentiation of benign from malignant disease has emerged as an important diagnostic challenge in the current age of health-care cost containment. Most physicians today acknowledge that early and accurate detection of cancer is important in successful treatment. Antibodies have been developed, labeled with radioactive isotopes, and used to detect and treat malignant tumors. During the past few years, several radiolabeled antibodies have received approval from the U.S. Food and Drug Administration for imaging colorectal, lung, ovarian, and prostate carcinomas, thus expanding and improving the physician's ability to detect and follow cancer in patients. At present, there is ample evidence in the literature to suggest that imaging with the ^IIIIn-labeled monoclonal antibody B72.3 is clinically useful for detecting primary/recurrent colorectal and recurrent ovarian carcinomas. In this article, we present a retrospective review of 136 patients from 10 moderate-sized hospitals who underwent a study with radioimmunoscintigraphy (R1S), using the ^IIIIn B72.3 antibody and standard diagnostic examinations for the detection of recurrent colorectal or ovarian carcinoma. The resulting data were analyzed in an effort to determine if (and how) information obtained from this radioimmunoscinti-graphic procedure is being used by referring physicians. Our findings suggest a gradually increasing use of scan findings with the ^IIIIn B72.3 antibody in making patient-management decisions.     

Influence of Cocktails of Labeled Monoclonal Antibodies on the Localization of Antibodies in Human Tumor Xenografts

In order to evaluate the usefulness of cocktails of labeled monoclonal antibodies (MoAbs) recognizing different antigen molecules to localize human cancer xenografts, we have compared the potential of three MoAbs recognizing representative cancer-associated CA 19–9, 17–1A and CEA antigens when administered alone or in combination. Specific binding of radioiodinated F(ab')₂ fragments of these three MoAbs was observed to human colorectal cancer cell lines SW1116, LS180 and Co-3. The percentage of in vitro cell binding of a cocktail of any two MoAbs to cancer cells was equal to the average of those obtained with the two MoAbs alone. The three MoAbs were preferentially localized in tumor tissues xenografted in nude mice. When cocktails of any two MoAbs were used, the obtained tumor-to-normal tissue ratios and percent of injected dose per gram of tumor were between the levels obtained for each MoAb when administered alone, in all three tumors transplanted in nude mice. These data suggest that, although cocktails of labeled MoAbs recognizing different antigens may extend the spectrum of tumor specificities, their use does not improve the tumor localization ability of MoAb-conjugates.     

Intravesical Administration of Radiolabelled Tumour-associated Monoclonal Antibody in Bladder Cancer

Considerable progress has been made over the past decade in the use of tumour-associated monoclonal antibodies (mAbs) as carriers of cytotoxic agents in the management of several malignancies. In the present study we investigated the tumour localization and biodistribution of the mAb HMFG1 to bladder cancer following intravesical administration. HMFG1, which has been raised against the polymorphic epithelial mucin (PEM), was labelled with ¹²⁵     

叶酸结合蛋白1、间皮素在卵巢癌组织中的表达及临床病理意义

目的 分析叶酸结合蛋白1(FOLR1)、间皮素(MSLN)在卵巢癌组织中表达的变化及临床病理意义.方法 回顾性分析2014年7月至2019年9月西平县人民医院收治的90例卵巢癌患者的临床资料,收集术后切除的癌组织制成标本,同时选择交界性卵巢肿瘤组织标本15例、正常卵巢组织标本30例作为对照.采用免疫组化染色检测并比较分...     

Inhibition of tumor cell growth in vitro by murine monoclonal antibodies that recognize a proliferation-associated cell surface antigen system in rats and humans

The mouse monoclonal antibody (MoAb) B3 raised against a rat bladder cancer cell line and the MoAbs HBJ127 and HBJ98 raised against a human bladder cancer cell line recognize homologous antigens predominantly present on proliferating cells of the corresponding species. Examination of MoAb-defined antigen and epitopes revealed that both HBJ127 and HBJ98 MoAbs defined a human cell surface glycoprotein complex having an apparent molecular weight of 125,000-130,000 which was composed of a heavy subunit of a glycoprotein nature (Mr 90,000-95,000) and a disulfide-linked light subunit of protein nature (Mr 30,000-35,000), but the HBJ127 and HBJ98 MoAbs recognized a protein epitope and a sugar epitope on the heavy subunit, respectively. Likewise, the B3 MoAb recognized a protein epitope on the heavy subunit of a rat cellular glycoprotein complex of similar composition to the HBJ127/HBJ98-defined human antigen. Addition of the B3 MoAb to rat and the HBJ127 or HBJ98 MoAb to human tumor cells inhibited the nucleic acid synthesis or the proliferation of the tumor cells in vitro in a dose-dependent manner. The target tumor cells exposed to MoAb could regrow when they were freed from the antibody, indicating that the effect of these MoAbs on the tumor cells is cytostatic and reversible. These MoAbs did not cause down-regulation of the cell surface antigen and did not arrest the cell cycle in a certain phase. These observations indicate that the Mr 125,000 glycoprotein cell surface component detected in both rat and human systems may play a requisite role for cell proliferation and that our MoAbs could inhibit the function by binding to the functionally proximal region of the component.     

Image Subtraction Analysis with Technetium-99M Labeled Monoclonal Antibody and Colloid for Evaluation of Liver Lesions: Phantom Measurements and Patient Studies

The ideal radiolabeled monoclonal antibodies (MoAbs) against cancer antigens are taken up by liver metastases; the background activity of normal liver, however, causes problems for delineation and detectability. In order to study these phenomena, a liver phantom containing hot and cold lesions of different sizes (diameters 5-32 mm) was constructed. It was placed into an elliptic cylindrical container representing a cross section of the abdomen. The specific activities in hot lesions varied from 1.85 to 14.8 MBq/ml, whereas liver phantom and cylinder activities were kept constant during different measurements. Lesions of size 1.3 cm³ could be detected without any subtractions, if the signal to background ratio was larger than 1.2. Lesions larger than 5 mm in diameter could also be detected using subtraction, which gave additional information by a factor 2-9, when the lesion sizes varied from 0.3 to 5.3 cm³ and when the specific activity in the lesions was at least twice as high as in adjacent liver. This subtraction technique was applied in 32 breast and lung cancer patients after injecting about 1 000 MBq ^99mTc-labeled anti-CEA MoAb; 24 h after the antibody injection 75 MBq ^99mTc-phytate was injected. The phytate + residual MoAb image was subtracted from the original antibody image. Thirteen patients had liver metastases verified by (CT, US), but only four patients had clearly observable abnormal liver uptakes in planar MoAb images. In 9 cases, additional information concerning liver metastases was obtained by subtraction technique. To judge by our phantom measurements the enhanced detectability was not an artefact.     

AGR2、CD3在卵巢交界性肿瘤鉴别诊断中的价值分析

目的:检测卵巢交界性肿瘤患者血清中前梯度蛋白2（AGR2）、CD3+T细胞水平,并探讨血清中两者水平对卵巢交界性肿瘤鉴别诊断的价值。方法:选取2017年07月至2019年12月本院收治并明确诊断的49例卵巢交界性肿瘤患者为研究对象（卵巢交界性肿瘤组）;同期选取68例良性上皮性肿瘤患者为对照（良性上皮性肿瘤组）,最终诊断由病理结果作为依据。两组患者一般资料分析。采用酶联免疫吸附法（ELISA）法检测患者血清中AGR2水平,流式细胞仪检测患者血清中T细胞亚群CD3+T细胞、CD4+T细胞、CD8+T细胞水平;分析影响卵巢交界性肿瘤发生的因素;采用受试者工作特征曲线（ROC曲线）分析AGR2、CD3+T细胞水平对卵巢交界性肿瘤的诊断价值。结果:两组患者年龄、孕次、产次、临床表现比较,差异均无统计学意义（P＞0.05）。卵巢交界性肿瘤组患者AGR2水平显著高于良性上皮性肿瘤组,CD3+T细胞、CD4+T细胞、CD8+T细胞水平显著低于良性上皮性肿瘤组（P＜0.05）;患者AGR2水平是发生卵巢交界性肿瘤的危险因素,CD3+T细胞水平是发生卵巢交界性肿瘤的保护因素（P＜0.05）,血清AGR2、CD3+T细胞水平诊断卵巢交界性肿瘤的曲线下面积（AUC）分别为0.833（95%CI:0.750~0.925）、0.800（95%CI:0.721~0.879）,特异性分别为98.5%、79.4%,敏感度分别为65.3%、67.3%;二者联合诊断卵巢交界性肿瘤的AUC为0.892（95%CI:0.828~0.956）,特异性为94.1%,敏感度为73.5%。结论:血清中AGR2、CD3+T细胞水平参与了卵巢交界性肿瘤病情的发生、发展,对卵巢交界性肿瘤的诊断有一定的潜在应用价值。     

Whole body positron emission tomography with 18F-fluoro-2-deoxyglucose for the detection of recurrent ovarian cancer

Although many cancers can be detected by whole-body positron emission tomography (PET) with 18F-fluoro-2-deoxyglucose (FDG), there has been limited clinical experience with FDG-PET for the detection of recurrent ovarian cancers. Therefore, the aim of this study was to evaluate the clinical value of FDG-PET in the detection of recurrent ovarian cancer. Whole body FDG-PET scans were performed on 24 women who had previous histories of ovarian cancer and treatment with surgery and chemotherapy. All patients also underwent physical examination, laboratory testing of serum CA-125 level and pelvic-abdominal-chest computed tomography (CT) or magnetic resonance imaging (MRI). The results of FDG-PET scans were correlated with serum CA-125 level, CT/MRI and operative pathology results. The diagnostic sensitivity was 90.9%, 90.9% and 90.9%, specificity was 92.3%, 76.9% and 46.2% and accuracy was 91.7%, 83.3% and 66.7% for FDG-PET, serum tumor marker of CA-125 level and CT/MRI in detecting recurrent ovarian cancer, respectively. FDG-PET is a useful diagnostic tool in detecting recurrent ovarian cancers with high specificity as compared with the serum tumor marker CA-125 level and the conventional CT/MRI morphological imaging methods.     

Increased tumor localization by monoclonal antibody A7 after F(ab')2 fragmentation in athymic nude mice bearing human pancreatic carcinomas

Much recent research has been directed toward the use of monoclonal antibodies (MoAbs) for the immunodetection of solid tumors. In pancreatic cancer, conventional immunoscintigraphy using intact MoAbs remains disappointing. In this study, ¹²⁵I-labeled F(ab')₂ fragments produced by pepsin digestion of MoAb A7 were injected intravenously into nude mice bearing human pancreatic cancer, HPC-YS, xenografts that have previously been shown to react specifically with MoAb A7. The tumor tissue/blood ratio of ¹²⁵I-labeled F(ab')₂ fragments of MoAb A7 increased with time and was much higher than those for normal tissues. Moreover, the tumor tissue/blood ratio of ¹²⁵I-labeled F(ab')₂ fragments was greater than that of intact MoAb A7, although the F(ab')₂ accumulation was less than that of intact MoAb A7 in the tumor. These results suggest that F(ab')₂ fragments of MoAb A7 may be suitable carriers of radionuclides for immunodetection of human pancreatic cancer. © 1993 Wiley-Liss, Inc.     

CT导向下125Ⅰ粒子植入治疗晚期头颈肿瘤的近期疗效

目的:评价CT导向下¹²⁵Ⅰ放射性粒子植入治疗晚期头颈肿瘤的临床价值。方法:回顾分析2007年10月-2008年8月接受CT导向下¹²⁵Ⅰ放射性粒子植入治疗的10例晚期头颈癌患者的临床资料。采用计算机立体计划系统计算布源,在CT导向下¹²⁵Ⅰ粒子平面插植。手术结束后1-3个月复查CT。结果:10例患者中8例术后5-14天疼痛缓解,有效率80%,2例无效。10例患者局部肿瘤完全缓解8例（80%）,部分缓解1例,无效1例。无明显并发症发生。结论:¹²⁵Ⅰ粒子植入治疗晚期头颈肿瘤近期疗效好,安全性高,创伤小,并发症发生率低。     

Clinical value of proton magnetic resonance spectroscopy for differentiating recurrent or residual brain tumor from delayed cerebral necrosis

: Delayed cerebral necrosis (DN) is a significant risk for brain tumor patients treated with high-dose irradiation. Although differentiating DN from tumor progression is an important clinical question, the distinction cannot be made reliably by conventional imaging techniques. We undertook a pilot study to assess the ability of proton magnetic resonance spectroscopy (¹H MRS) to differentiate prospectively between DN or recurrent/residual tumor in a series of children treated for primary brain tumors with high-dose irradiation.

: Twelve children (ages 3–16 years), who had clinical and MR imaging (MRI) changes that suggested a diagnosis of either DN or progressive/recurrent brain tumor, underwent localized ¹H MRS prior to planned biopsy, resection, or other confirmatory histological procedure. Prospective ¹H MRS interpretations were based on comparison of spectral peak patterns and quantitative peak area values from normalized spectra: a marked depression of the intracellular metabolite peaks from choline, creatine, and N-acetyl compounds was hypothesized to indicate DN, and median-to-high choline with easily visible creatine metabolite peaks was labeled progressive/recurrent tumor. Subsequent histological studies identified the brain lesion as DN or recurrent/residual tumor.

: The patient series included five cases of DN and seven recurrent/residual tumor cases, based on histology, The MRS criteria prospectively identified five out of seven patients with active tumor, and four out of five patients with histologically proven DN correctly. Discriminant analysis suggested that the primary diagnostic information for differentiating DN from tumor lay in the normalized MRS peak areas for choline and creatine compounds.

: Magnetic resonance spectroscopy shows promising sensitivity and selectivity for differentiating DN from recurrent/progressive brain tumor. A novel diagnostic index based on peak areas for choline and creatine compounds may provide a simple discriminant for differentiating DN from recurrent or residual primary brain tumors.     

Coordinate elevation of serum markers in ovarian cancer but not in benign disease

Effective screening for occult ovarian cancer will require a strategy that is both sensitive and specific. Preliminary data suggest that CA 125 is elevated at diagnosis in a majority of patients with ovarian cancer. Although CA 125 is sufficiently specific to prompt its evaluation as one component of a strategy to detect ovarian cancer in postmenopausal women, a further improvement in specificity would facilitate cost-effective screening. In an attempt to develop a more specific screening strategy, multiple markers were assayed in a panel of sera from 47 patients with ovarian cancer and in a separate panel of sera from 50 individuals with benign disease whose serum CA 125 levels exceeded 35 U/ml. Among the patients with ovarian cancer, elevations of CA 125 (greater than 35 U/ml) were observed in 91%, CA 15-3 (greater than 30 U/ml) in 57%, TAG 72 (greater than 10 U/ml) in 49%, placental alkaline phosphatase (PLAP) in 25%, human milk fat globule protein (HMFG) 1 in 77%, HMFG2 in 62%, and NB/70K in 57%. Among the 50 sera selected from patients with benign disease, CA 125 was more than 35 U/ml in 100% and more than 65 U/ml in 42%. Among those patients with benign disease and elevated CA 125, NB/70K was elevated in 62%, HMFG1 in 26%, and HMFG2 in 12%, whereas TAG 72 and CA 15-3 were elevated in only 6% and 2%, respectively. In addition PLAP appeared promising; elevated enzyme levels were not found in the benign disease group. Among patients with ovarian cancer with CA 125 levels more than 35 U/ml, either TAG 72 or CA 15-3 was elevated in 77%. In the false-positive group, only 6% had elevations of one or the other marker. The CA 125 levels in cancer patients were, however, substantially greater than in patients with benign disease. If sera from patients with ovarian cancer were diluted to a range comparable to that found in benign disease, at least one of the two confirmatory tests was elevated in 63% of the samples from the malignant cases. Consequently, use of CA 15-3 and TAG 72 in combination with CA 125 can increase the apparent specificity of the CA 125 assay for distinguishing malignant from benign disease. Prospective studies will be required to test critically whether the use of additional serum markers in combination with the CA 125 assay would contribute to the specificity of a cost-effective screening strategy for ovarian cancer.     

两种方法检测血清人附睾分泌蛋白在盆腔疾病诊断中的研究

  目的  探讨血清人附睾分泌蛋白(human epididymis protein 4, HE4)在盆腔疾病诊断及鉴别诊断中的应用价值, 比较电化学发光法(electrochemiluminescence immunoassay, ECLIA)及酶联免疫吸附法(Enzyme-linked immunosorbent assay, ELISA)检测人附睾分泌蛋白的诊断准确性。  方法  采用ECLIA检测211例患者血清HE4水平, 包括85例卵巢癌、42例子宫内膜癌、21例子宫内膜异位症、33例盆腔良性疾病及30例健康对照者。结果以中位数表示, 分析血清HE4在盆腔疾病诊断及鉴别诊断中的意义, 并分别探明诊断卵巢癌及子宫内膜癌的最佳判定值。采用ELISA对其中卵巢癌组及卵巢良性疾病组血清HE4进行检测, 绘制受试者工作特征曲线(ROC), 计算曲线下面积(ROC-AUC), 比较两种方法鉴别诊断卵巢良恶性疾病的准确性。  结果  卵巢癌组、子宫内膜癌组血清HE4水平显著高于健康对照组、卵巢良性疾病组及子宫内膜异位症组; 卵巢良性疾病组及子宫内膜异位症组与健康对照组比较, 无显著性差异; HE4在鉴别诊断卵巢良恶性疾病、子宫内膜良恶性疾病时, 其ROC-AUC分别为0.869和0.931, 最佳诊断点分别为86.02 pmol/L和74.6 pmol/L。以卵巢良性肿瘤组作为对照, ECLIA法及ELISA法检测卵巢癌患者血清HE4的ROC-AUC分别为0.869和0.794。  结论  HE4在盆腔疾病的诊断及良恶性鉴别中具有较高的诊断价值, ECLIA法检测卵巢癌的诊断准确性优于ELISA法。      

Intraperitoneal xenografts of human epithelial ovarian cancer in nude mice

Using continuous human ovarian cancer cell lines, i.p. xenografts were successfully established in nude mice from four of four attempts. When primary tumor material was used, xenografts grew in 8 of 10 attempts. From these eight, three passageable xenograft cell lines have been established. To our knowledge, this is the first report published of such xenografts. I.p. xenografts closely mimic the clinical behavior of human ovarian cancer, and those developed from primary tumor material maintain close morphological similarity to the parent primary tumor. When expression of placental alkaline phosphatase and the tumor associated antigens defined by the monoclonal antibodies HMFG1, HMFG2, AUA1, and F36/22 by these models was determined, those i.p. xenografts derived from primary tumor material exactly matched the original tumor, while none of the xenografts derived from the cell lines expressed these antigens. These models will be useful for investigating the biology and treatment of ovarian cancer.     

A thousand points of light or just dim bulbs? Radiolabeled antibodies and colorectal cancer imaging.

Radioimmunoscintigraphy (RIS) is coming into its own as an imaging modality in clinical oncology. Early experience with indium-111-labeled intact murine monoclonal antibodies (MoAbs) in colorectal cancer suggested that RIS images hepatic metastases poorly. Moreover, an antimurine immune response was frequently provoked, precluding multiple follow-up RIS studies in individual patients due to reticuloendothelial sequestration of the radioimmunoconjugate before tumor targeting could occur. Recent trials of technetium-99m-labeled antibody fragments and human MoAbs have demonstrated significant improvement in imaging efficacy, and repeated or serial imaging is possible because of the absence of associated immunogenicity. RIS is demonstrably more sensitive than conventional diagnostic modalities (CDM) such as computed tomography (CT) for detection of extrahepatic abdominal and pelvic colorectal carcinoma and is complementary to CDM in imaging liver metastases. In a surgical decision-making analysis comparing CT, RIS (IMMU-4 99mTc-Fab'; CEA-Scan), and CT plus RIS in patients with recurrent or metastatic colorectal cancer, CT plus RIS improved correct prediction of resectability by 40% and correct prediction of unresectability by 100% compared with CT alone. At the present time, RIS used in combination with CDM contributes an incremental improvement in diagnostic accuracy in colorectal cancer patients with known or suspected recurrent disease. Basic and clinical research currently in progress promises to yield agents and methods that provide rapid high-resolution imaging, high tumor-to-background ratios in all organs at risk for tumor recurrence or metastasis, negligible immunogenicity and toxicity, and a significant further improvement in the accuracy of clinical decision making in oncology patients.     

Localization and imaging of radiolabeled monoclonal antibodies against colorectal carcinoma in tumor-bearing nude mice

Four monoclonal antibodies (MoAbs) (35, 115, 17-1A, and B72.3) directed towards human carcinoma surface antigens have been studied in athymic nude mice with LS174T, CO112, or SW948 colon carcinoma xenografts or negative control melanoma (MEL-1), lymphoma (Namalwa), and breast (MCF-7) carcinoma xenografts to evaluate the effects of antigenic heterogeneity and time after administration on localization and imaging. 125I-labeled 115 showed the highest uptake of any antibody in LS174T tumors. MoAbs 35 and B72.3 showed similar but lower levels of uptake in LS174T and CO112 tumors, but B72.3 concentrated less in SW948 tumors. 17-1A showed the highest degree of accumulation in SW948 tumor xenografts. No specific uptake of the four anti-carcinoma MoAbs was observed in MEL-1, Namalwa, or MCF-7 xenografts. The specificity of the in vivo tumor localization of the four anti-carcinoma MoAbs was confirmed by the low degree of accumulation of a control MoAb against influenza virus in LS174T tumors. Imaging studies with 131I-labeled colorectal cancer MoAbs showed specific uptake and retention in LS174T tumors, with progressive clearance from the whole body. The colorectal cancer MoAbs were compared for immunohistochemical binding against biopsies from patients with colorectal cancer and adjacent normal colonic tissue. Most colorectal cancer specimens showed moderate to strong staining with the four MoAbs. The percentage of positive cells varied within and between tumors demonstrating antigenic heterogeneity. Absent to slight focal staining was seen with normal colon tissue. B72.3 showed the highest degree of staining specificity. This study indicates a difference in the immunohistochemical binding of a panel of MoAbs against biopsies of colon adenocarcinoma and a dependence of in vivo localization on the human colon cancer cell line used as target. This has important implications for future clinical diagnostic and therapeutic studies.