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PubMed1993

Biomolecular and clinical characteristics of PSA and other candidate prostate tumor markers.

Three new potential biomarkers--PAC, PMA, and the 7E11-C5 glycoprotein--have been identified. All three have unique features that could augment current diagnostic and therapeutic modalities. Some of the important characteristics of these potential markers are summarized in Table 1. Further studies will be required to determine if any of them will provide clinical information beyond that provided by PSA and if they will have a significant impact on the management of patients with prostate cancer. The MAb 7E11-C5 (CYT-356), now in clinical trials, promises to offer new strategies for radioimmunodetection and radioimmunotherapy of prostate cancer.

Antigens, Neoplasm↗
PubMed1995

Reduction of the renal uptake of radiolabeled monoclonal antibody fragments by cationic amino acids and their derivatives.

The renal uptake of radiolabeled antibody fragments and peptides is a problem in radioimmunodetection and radioimmunotherapy, especially with intracellular retained radiometals. The aim of this study was to develop suitable methods to reduce this kidney uptake. BALB/c mice or nude mice bearing the human GW-39 colon carcinoma xenograft were given i.p. injections of basic amino acids or a range of different basic amino acid derivatives, amino sugars, as well as cationic peptides. The effect of these agents on the biodistribution of Fab' and F(ab')2 fragments of different mAbs radiolabeled with 99mTc, 188Re, 111In, 88Y, or 125I was studied. Tumor and organ uptake was determined and compared to untreated mice. The kidney uptake of Fab' fragments was reduced 5-6-fold in a dose-dependent manner as compared to untreated controls. The uptake in all other organs, as well as the tumor, was unaffected. A similar reduction in renal retention was seen for all other intracellularly retained isotopes, as well as for F(ab')2 fragments. D- and L-isomers of lysine were equally effective whether given i.p. or p.o. D-glucosamine was effective, but its N-acetyl derivative was not. Basic polypeptides (e.g., poly-L-lysine) were also effective; their potency increased with increasing molecular weight. HPLC of the urine taken from treated animals showed the excretion of intact Fab', in contrast to mostly low-molecular-weight metabolites in the control group. These studies indicate that a variety of basic compounds is capable of inhibiting the tubular reabsorption of peptides and proteins, thus lowering the kidney uptake of antibody fragments significantly. On a molecular basis, the effect seems to essentially rely on the presence of a positively charged amino group. By reducing renal retention of antibody fragments, their role as imaging and therapeutic agents may be expanded.

Animals↗
PubMedDate not supplied

Correlation of cell proliferation marker (TPS), natural killer (NK) activity and tumor load serotest (PSA) in untreated and treated prostatic tumors.

Tissue polypeptide specific antigen (TPS) is a new tumor proliferation serotest marker. The respective radioimmunodetective procedure is based on the application of monoclonal antibodies raised against one the principle epitopes of tissue polypeptide antigen (TPA). TPS is useful tool for the identification of proliferative epithelial cells and is negative in all non-epithelial tissues such as lymph nodes, bone marrow, carcino-sarcomic and neuroendocrine prostatic tumors. In previous studies we have shown the clinical usefulness of this serotest in serial measurements during prostate cancer monitoring. In this study serum prostatic specific antigen (PSA) concentrations and natural killer (NK) cell activity data were compared with serum TPS values in a wide spectrum of prostate cancer condition (99 patients), benign prostatic hypertrophy (BPH, 40 patients), atypical prostate (12 subjects) and in 8 healthy men. Measured parameters reflect different aspects of the disease. Blood PSA concentrations and TPS serotest values were found to denote the status of disseminated prostate cancer with nearly equal significance, while PSA appears to be a more appropriate tumor marker in early stages of the disease. In atypical prostate a nonsignificant elevation of both PSA and TPA values were recorded when compared with BPH. In parallel, a pronounced and sharp drop in NK activity data was assessed resembling closely respective data in progressive Stage D2 patients. TPS serotest clearly detects cancer progression in treated and untreated patients (P < 0.01) while being less efficient in distinguishing between tumor stabilization and partial remission (p > 0.05). In this respect NK activity data serve as a sensitive probe for the presence of epithelial tumor cells in the circulation even during stabilization of the disease. According to the reported results we advocate the application of the TPS serotest as a useful addition in monitoring progressive patients with advanced prostatic carcinoma.

Antigens, Neoplasm↗
PubMedDate not supplied

Serial measurements of tissue polypeptide specific antigen (TPS), PSA, PAP and CEA serotest values in treated patients with primary and metastatic prostate cancer.

Blood tissue polypeptide specific antigen (TPS) concentration was serially measured by IRMA radioimmunodetective procedure in hormonally treated prostate cancer patients with Stage Do-D1 tumor (20 subjects free of bone lesions) and Stage D2 disease (20 subjects with bone metastases). Monoclonal antibody against the principle M3-TPA epitope was used in this TPS assay. Serum TPS values were compared with respective blood prostate specific antigen (PSA), prostatic acid phosphatase (PAP), carcinoembryonic antigen (CEA) and testosterone levels in a retrospective manner. A control group included healthy men, patients with benign prostatic hypertrophy (BPH), subjects with inflammation of the prostate, and men with diabetes. PSA is reported to be a quantitative calibration for prostate cancer load in untreated patients, especially during early stages of the disease. In hormonally treated, advanced, and dedifferentiated prostatic carcinoma this serotest fails to reflect properly both tumor status and response to treatment. In Stage Do-D1 patients TPS concentrations remain normal or become slightly elevated even during local tumor progression. This finding is in accord with the slow proliferation of nonaggressive primary tumors. Circulating TPS concentrations are elevated in progressive metastatic patients, in the majority of Stage D2 subjects with stable disease and even in some of these patients during partial tumor remission. This latter result may be attributed not only to the heterogeneity of the advanced prostatic cancer but also to the actual tumor response to treatment, since serum PSA level fails to reflect properly the outcome of hormonal treatment. There is some evidence that an abrupt elevation in serum TPA level in such patients is a consequence of NK cell-mediated lysis of circulating tumor cells, thus giving rise to a simultaneous and rapid delivery of intracellular TPS into the bloodstream. Prostatic inflammation elevates TPS concentrations only slightly, while diabetes, even during a proper treatment, raises TPS concentration more intensely. In patients with BPH normal or slightly increased TPS values were measured. The results ot these preliminary investigations seem to open the way for further prospective studies.

Acid Phosphatase↗
PubMed1993

[Biodistribution of 125I labeled monoclonal antibody against gamma seminoprotein in the nude mice bearing human benign prostatic hyperplasia xenografts].

The biodistribution of 125I labeled monoclonal antibody against gamma seminoprotein (gamma-Sm) in the nude mice bearing human benign prostatic hyperplasia xenograft was evaluated by whole body autoradiography and by counting of radioactivity in organs. The monoclonal antibody (murine Ig G1, K) to gamma-Sm which was established in this institute and its F(ab')2 fragment were radioiodinated using Iodogen method. The autoradiograms demonstrated specific uptake of 125I-intact Ig G as well as 125I-F(ab')2 within the prostatic adenoma xenografts 4 days after intravenous administrations. Radioactivity in the xenograft was relatively higher than those in the liver, kidney or lung. These results suggest that radio-labeled monoclonal antibody against gamma-Sm might be applicable for radioimmunodetection of prostatic tumors which produce gamma-Sm.

Adenoma↗
PubMedDate not supplied

Biological response modifiers as adjuvants in monoclonal antibody-based treatment (review).

Compelling experimental evidence suggest that the use of differentiation-inducing agents which enhance tumor antigen expression may play a pivatal role in MAb-based approaches to tumor diagnosis and/or therapy. In particular, interferons can up-regulate CEA and TAG-72 expression on the surface of human carcinoma cells which leads to an enhanced MAb tumor localization. The ability to target additional MAb to the tumor site has subsequently been shown to augment radioimmunodetection and therapy in experimental models. Initial clinical studies reported that interferon administration to patients diagnosed with malignant melanoma improved the tumor distribution of antimelanoma MAb without an accompanying increase of antibody in normal tissues. The findings from our phase 1A trial clearly showed that intracavitary IFN-gamma administration augmented TAG-72 and CEA expression on carcinoma cells isolated from malignant ascites from patients diagnosed with ovarian or gastrointestinal cancer. Future efforts need to further investigate the molecular mechanisms involved in the regulation of these and other human tumor antigens by the interferons as well as other differentiation-inducing agents. Additional clinical studies should evaluate the overall effectiveness of combining an antigen up-regulation protocol with a conjugated MAb in the hope of improving tumor diagnosis and therapy.

Adjuvants, Immunologic↗
PubMed1996

Breast carcinoma detection with a combination of radiolabeled monoclonal antibodies. Promising results from immunohistochemistry studies.

BACKGROUND: Recent studies have demonstrated that the use of radiolabeled monoclonal antibodies (MoAbs) directed against tumor-associated antigens could help in the recognition of primary tumors, their extent, and their metastases by external scintigraphy (used preoperatively) or by hand-held gamma-detecting probe (GDP) (used intraoperatively). METHODS: The authors evaluated carcinoembryonic antigen (CEA), c-erb B-2 protein, and TAG-72 expression in 100 cases of breast carcinoma using F023C5 (anti-CEA), B72.3, and anti-c-erb B-2 protein MoAbs that were previously investigated for their usefulness in radioimmunoguided surgery and external scintigraphy. The goal of this study was to examine the biodistribution of each antibody in primary, multifocal, and metastatic lesions to evaluate the suitability of their simultaneous use in GDP and external scintigraphy. RESULTS: Results showed immunoreactivity for c-erb B-2 protein in 39 of 99 cases, for B72.3 in 41 of 100 cases, and for CEA in 15 of 100 cases. Multifocal lesions demonstrated positivity for c-erb B-2 protein in 37.4% of cases (6 of 16), for B72.3 in 68.8% of cases (11 of 16), and for CEA in 6.2% of cases (1 of 16). In lymph node metastases, immunoreactivity was found for c-erb B-2 protein in 36.4% of cases (12 of 33), for B72.3 in 63.7% of cases (21 of 33), and for CEA in 24.3% of cases (8 of 33). When the authors considered the immunoreactivity of all three MoAbs, the percentage of positive cases they observed was 60% in primary tumors (60 cases), 78% in lymph node metastases, and 81.2% in multifocal lesions. CONCLUSIONS: These results suggest that in vivo tumor radioimmunodetection could be improved by the use of more antibodies directed against different tumor-associated antigens.

Antibodies, Monoclonal↗
PubMed1997

Analysis of specific accumulation of radiolabeled anti-carcinoembryonic antigen monoclonal antibody CEA 102 in colorectal cancer using computed radiography.

The specific accumulation of radiolabeled anti-carcinoembryonic antigen (CEA) monoclonal antibody (MoAb) CEA 102 in colorectal cancers was investigated by autoradiography of surgical specimens using Fuji Computed Radiography (FCR). Five patients with colorectal cancer were injected intravenously with [13I]-labeled intact CEA 102 or its F(ab')2. Primary tumor and liver metastases were successfully detected by external scanning with gamma camera in four cases. Autoradiographic study using FCR showed predominant localization of [13I]-labeled CEA 102 in primary tumors and liver metastases in all cases. Even the small-sized liver metastasis (0.5 cm) was clearly visualized. The pixel distribution curves showed the heterogeneity of the distribution of administered MoAb in the tumors. In the quantitative distribution analysis of CEA 102, the uptake of the primary tumor was 10-fold greater than that of the normal colon mucosa. These results suggest that MoAb has great potential in radioimmunodetection as well as possible use in antibody-directed therapy.

Antibodies, Monoclonal↗
PubMed1995

Utility of scintigraphic methods in patients with fever of unknown origin.

BACKGROUND: We assessed the utility of scintigraphy with indium 111-labeled polyclonal human IgG scintigraphy in patients with fever of unknown origin that fulfilled the criteria of temperature of 38.3 degrees C or more for at least 3 weeks and no diagnosis during 1 week of hospital admission. We compared the utility of this technique with results of scintigraphic techniques reported in the literature. METHODS: Data for all patients seen at our university hospital in whom 111In-IgG scanning was performed were analyzed and checked for the criteria for fever of unknown origin. The literature on the utility of scintigraphic techniques in patients with fever of unknown origin was reviewed. RESULTS: We studied 24 patients with fever of unknown origin. In 13 patients, focal 111In-IgG accumulation was observed. In nine (38%) of those, the positive 111In-IgG scintigram led to the final diagnosis; in the other four patients (17%), the scintigraphic findings were not helpful. In the 11 patients with negative 111In-IgG scans, extensive diagnostic workup produced no infection as the final diagnosis in nine patients (38%), one had an abscess in a renal cyst that was detected several months later, and in the other the cause of fever was an infected intravenous line. The overall sensitivity and specificity of 111In-IgG scintigraphy were 81% and 69%, respectively. The positive predictive value was 69% and the negative predictive value was 82%. CONCLUSIONS: Our results show that 111In-IgG scintigraphy significantly contributed to the diagnostic process in patients with fever of unknown origin. A positive scan increased the likelihood of finding the cause of the fever, and a negative scan ruled out an inflammatory component with a high degree of certainty. These data compare favorably with data in the literature concerning other radiopharmaceuticals; a larger prospective evaluation of this technique is indicated.

Adult↗
PubMed1996

False tumor-positive lymph nodes in radioimmunodiagnosis and radioimmunoguided surgery: etiologic mechanisms.

We investigated the causes of false-positive (nontumor cell) focal uptake in radioimmunodiagnosis (RAID) and false-positive high counts in radioimmunoguided surgery (RIGS). Tissue blocks of two such RAID cases were recut and examined by immunohistochemistry (IH) (group 1). Lymph nodes in the drainage area of 14 colon cancers selected because of tumor-positive draining nodes were examined similarly (group 2). The lymph nodes in group 1 showed nontumor cell germinal center (GC) and rare macrophage (M phi) positivity with monoclonal antibody (mAb) CC49 to tumor antigen (Ag) TAG-72, the same Ag to which the mAb B72.3, used for the RAID studies, was directed. In group 2, CC49 staining was observed in the colon cancers, in noncellular tumor Ag in lymphatic channels, and in the GC of draining nodes in a pattern similar to that of follicular dendritic cells (FDC). An In-111-mAb/tumor Ag (TAG-72 or CEA) complex can result in false-positive RAID/RIGS studies by In-111 retained in the lysosomes of lymph node M phi, following attachment of the mAb to the Ag, and their catabolism in the M phi. An I-125-mAb to either tumor Ag could lead to false positive RIGS studies due to its attachment to the Ag portion of ag/ab complexes affixed to the FDC in the GC of the lymph nodes draining a tumor.

Aged↗
PubMed1998

Radiolocalization of the sentinel lymph node in Merkel cell carcinoma: a clinical analysis of seven cases.

Merkel cell carcinoma (MCC) is a rare cutaneous skin lesion with a variable but often aggressive clinical course. Patient survival correlates with nodal status and the presence of distant metastases. The histologic status of the sentinel lymph node consistently correlates with the incidence of regional lymphatic metastases in other dermal malignancies. The technique of radiolocalization and surgical resection of the sentinel lymph node using an intraoperative gamma probe is used to guide clinical management in these patients. We report on seven cases of MCC managed utilizing this technique. Four patients had negative sentinel nodes and no other nodal disease at completion lymphadenectomy (n = 2) or clinical follow-up (n = 2) and currently remain disease free. Two patients had a positive sentinel node but no other positive lymph nodes at completion lymphadenectomy; one of them developed regional recurrence. One patient with a positive sentinel node and six additional positive nodes developed extensive nodal disease and systemic recurrence during radiotherapy and expired of MCC. Our results suggest that the sentinel node was identified and removed successfully using radiolocalization making this technique useful in the staging and therapy of patients with MCC.

Aged↗
PubMed1996

Intraoperative detection of occult colon cancer micrometastases using 125 I-radiolabled monoclonal antibody CC49.

BACKGROUND: The detection of locally-disseminated disease is one of the principal goals of oncologic surgery. For this study, a hand-held, gamma-detecting probe was used intraoperatively to assess the extent of colorectal carcinoma in patients previously injected with radiolabeled antibody to the TAG-72 antigen (CC49); this technique is known as Radioimmunoguided Surgery (RIGS) (Neoprobe Corporation, Dublin, OH). RIGS-positive areas (i.e. those with increased signal over background) have previously been shown to contain carcinoma in a high proportion of cases. However, some RIGS-positive areas had no tumor detectable by clinical examination or routine histopathologic analysis. This study was undertaken to determine if the presence of occult metastases might account for this disparity. METHODS: A total of 57 regional lymph nodes (LN), resected from 16 patients with primary (9) or recurrent (7) colorectal carcinoma, were studied. The patients were injected with 125I labeled CC49 murine monoclonal antibody approximately 3 weeks prior to surgery. After routine histologic evaluation, the LN were analyzed for occult metastases; paraffin sections were cut at 5 levels (50 micron apart) and were examined by histology (hematoxylin and eosin stain [H & E]) and by immunohistochemistry (IHC) with a cocktail of monoclonal antibodies to cytokeratins. RESULTS: Fifty-seven LN were included in this study; 17 were H & E-positive (i.e., contained tumor by routine histologic examination [overt tumor]), while 40 LN were H & E-negative (i.e., no evidence of tumor after routine histologic examination). Thirty-nine LN were RIGS-positive, but only 14 of these were H & E-positive. Of the 25 RIGS-positive/H & E-negative LN, 10 (40%) demonstrated the presence of occult metastases after serial section/IHC analysis. Thus, a total of 27 LN contained metastatic carcinoma (17 overt, 10 occult); routine histologic analysis was able to identify tumor in only 17 of these 27 LN (63%), while the probe signaled the presence of tumor in 24 of these LN (89%). None of the RIGS-negative/H & E-negative LN were found to have occult metastases (0/15). Specific immunoreactivity with CC49 antibody was observed in 5 of 15 RIGS-positive/H & E-negative LN in which no tumor could be identified by any method (histopathology or IHC. CC49 immunoreactivity was not observed in 15 RIGS-negative/H & E-negative LN. CONCLUSIONS: The finding of a RIGS-positive LN had a significant association with the presence of tumor cells (P < 0.05). In this study, the RIGS procedure was more sensitive than clinical or histopathologic examination in detecting the regional spread of a tumor. Furthermore, in LN that showed no evidence of tumor by routine histopathologic examination, a positive RIGS reading was significantly associated with the presence of occult LN metastases (P < 0.01). This study is the first to demonstrate the detection of histologically occult tumor by a remote imaging device. RIGS assessment is a highly sensitive method for detecting occult tumor deposits, and may guide therapeutic intervention in patients with colorectal carcinoma.

Antibodies, Monoclonal↗
PubMed1996

The role of radioimmunoscintigraphy and computed tomography scan prior to reassessment laparotomy of patients with ovarian carcinoma. A preliminary report.

BACKGROUND: Accurate evaluation of patients with ovarian carcinoma who have completed primary therapy often requires surgical exploration. Radioimmunoscintigraphy (RIS) represents an evolving technique that may allow noninvasive detection and localization of persistent or recurrent disease in these patients. METHODS: Our prospective, blinded study enrolled patients with normal CA 125 levels and no clinical evidence of disease after primary cytoreductive surgery and cytotoxic chemotherapy for ovarian carcinoma. Each patient underwent RIS using Indium-satumomab pendetide (labeled antibody B72.3 to the tumor-associated antigen TAG-72) and abdominal/pelvic computed tomography (CT) prior to reassessment laparotomy. RESULTS: Twenty patients were enrolled from January 1994 to January 1995. Two patients with negative RIS scans refused reassessment laparotomy and were without evidence of disease > 15 months from the study. Twelve of the remaining 18 patients (66.7%) had histologically proven disease at reassessment laparotomy. RIS images indicated the presence of disease in all 12 patients, whereas CT scans detected disease in only 2 patients. In three of five patients, biopsy-proven microscopic disease (no gross disease at the time of laparotomy) was found only in specimens obtained by RIS-directed biopsies. RIS was superior to CT in sensitivity (100% vs. 16.7%), accuracy (72% vs. 33%), and negative predictive value (100% vs. 28.6%) (P < 0.005). CONCLUSIONS: Routine use of CT is of limited value in the assessment of ovarian carcinoma patients with negative physical examinations and normal CA 125 levels. With its high level of sensitivity and negative predictive value, RIS may play a role in the detection of persistent disease in this population and aid in the classification of patients into three distinct groups: those with gross residual disease, small volume or microscopic disease, and no disease. Separation of this heterogenous group without surgery may help guide subsequent consolidation therapy. However, attaining a high level accuracy with RIS, depends on optimizing the method of image acquisition, the timing of scans, and the reconstruction of data.

Animals↗
PubMed1997

Radioimmunoscintigraphy with a novel monoclonal antiprostate antibody (E4): an experimental study in nude mice.

BACKGROUND: Prostate cancer is one of the leading causes of death among men, despite achievements in diagnosis and therapy. Radioimmunolocalization and radioimmunotherapy of malignant tumors have demonstrated increasing potential and may become useful tools in the management of prostate cancer. METHODS: Nude mice were inoculated subcutaneously with cells from the poorly differentiated human prostate cancer cell line DU-145. The intact monoclonal antibody (MoAb) E4 and an intact anticytokeratin-8 MoAb, TS1, used for comparison were labeled with 125I and injected intraperitoneally (i.p.) in the mice. Repetitive quantitative scintigraphic recordings were performed during 1 month. The mice were killed at Day 29 after injection of the radiolabeled MoAb. The tumors and the organs were dissected and weighed. The remaining activity was measured in a gamma well counter. One part of the tumor was immediately fixed in Bouin's solution for autoradiography and the other in formaldehyde for microscopy. RESULTS: The study demonstrated significant radioimmunolocalization of the MoAb E4 into the DU-145 prostate tumor tissue in the animal model, with an average radiation dose of 0.08 Gy/MBq in the tumor. TS1 localized preferentially in necrotic parts of the tumor, yielding a tumor dose of 0.02 Gy/MBq. CONCLUSIONS: The MoAb E4 is a promising radiotracer for prostate cancer and may be used in radioimmunotherapy. As in earlier studies, TS1 shows significant radioimmunolocalization into necrotic tumor tissue, which also exists in prostate cancer.

Animals↗
PubMed1997

Anti-carcinoembryonic antigen antibodies versus somatostatin analogs in the detection of metastatic medullary thyroid carcinoma: are carcinoembryonic antigen and somatostatin receptor expression prognostic factors?

BACKGROUND: Surgery is currently the only potentially curative approach in the treatment of medullary thyroid carcinoma (MTC). In many instances however, postsurgically elevated or rising plasma calcitonin and/or carcinoembryonic antigen (CEA) levels indicate persistent metastatic disease, although conventional diagnostic procedures (computed tomography (CT), magnetic resonance imaging (MRI), and invasive venous catheterization) fail to localize the responsible lesions. Recently, anti-CEA antibodies and somatostatin analogs have shown promising results in the staging of MTC. The aim of this study was to compare the sensitivity of both methodologies, especially for the detection of occult MTC, and to assess whether there may be correlations between the scintigraphic behavior and the patients' prognosis. METHODS: A total of 26 patients with medullary thyroid carcinoma were examined at our institution between 1977 and 1996. Ten of them had known disease, 14 had occult metastatic MTC, and 2 were free of disease at the time of presentation. Fourteen patients were investigated with anti-CEA monoclonal antibodies (MAbs) (receiving a total of 35 injections: clones BW431/26, BW431/31, IMACIS, or F023C5, labeled with 99mTc, (111)In or (131)I), and 8 patients were studied with (111)In-labeled octreotide. Two patients received potentially therapeutic doses of (131)I-labeled anti-CEA antibodies. All patients underwent conventional radiologic evaluation (ultrasonography, CT, and MRI) and/or biopsy within 4 weeks. Additional imaging was performed with 99mTc-(V)-DMSA, (131)I-metaiodobenzylguanidine, 201thallium chloride, 99mTc-methylene diphosphate, and/or 18F-fluorodeoxyglucose-positron emission tomography. Clinical follow-up was obtained. RESULTS: All patients with established disease had elevated plasma CEA (range, 6.8-345 ng/mL; calcitonin levels between 92 and 11,497 pg/mL), whereas in 9 of 14 occult cases, levels were < or = 5 ng/mL (range, 0.6-829 ng/mL; calcitonin, 72-2920 pg/mL). In patients with known disease, the overall lesion-based sensitivity was 86% for the anti-CEA MAbs, whereas octreotide was unable to target any tumor in patients with rapidly progressing disease or distant metastases (overall sensitivity, 47%). In all patients with occult MTC, anti-CEA MAbs and octreotide were able to localize at least one lesion (patient-based sensitivity, virtually 100%). In patients with postsurgically persistent hypercalcitoninemia, cervical lymph nodes were identified as the most frequent site of metastases, whereas in patients with occult and slowly progressing disease several years after primary surgery, anti-CEA MAbs and octreotide showed bilateral involvement of mediastinal lymph nodes; however, tumor to nontumor ratios were usually higher with octreotide in these cases. With anti-CEA Mabs, the highest tumor to nontumor ratios were observed in clinically aggressive, rapidly progressing disease. The sensitivity of all other diagnostic modalities was, at < or = 50%, significantly lower. Indication for antitumor effects was observed in a patient receiving 65 mCi of (111)I-labeled F(ab')2 fragments of the clone F023C5. CONCLUSIONS: For the detection of occult MTC, anti-CEA MAbs and octreotide seem to have a sensitivity that is superior to conventional diagnostic modalities, especially also when used in combination. Better detectability with anti-CEA antibodies (which may result in higher CEA expression) seems to be associated with more aggressively growing forms of MTC, whereas somatostatin receptor expression at normal CEA plasma levels and weaker MAb targeting may be associated with a more benign clinical course. This is in accordance with the study of Busnardo et al. (Cancer 1984; 53:278-85), who showed higher CEA serum levels to be associated with a worse prognosis, as well as with the in vitro findings of Reubi et al. (Lab Invest 1991;64:567-73), who demonstrated lower somatostatin receptor expression in less differentiated MTC. Fu

Adult↗
PubMed1997

Tc-99m LL-2 Fab' monoclonal antibody imaging in acquired immune deficiency syndrome-related lymphoma.

BACKGROUND: Both systemic and primary central nervous system (CNS) non-Hodgkin's lymphomas (NHL) occur in people with acquired immune deficiency syndrome (AIDS). The radiographic manifestations may be similar to other neoplasms and opportunistic infections that are also found frequently in AIDS. Furthermore, these diseases may coexist with NHL in the AIDS patient. METHODS: To evaluate the use of Tc-99m Lymphoscan (the Fab' fragment of the anti-CD-22 antibody LL-2; Immunomedics, Inc., Morris Plains, NJ) in patients with suspected AIDS lymphoma, we studied 7 patients with 35 sites of suspected disease. Six had CNS lesions suspicious for parenchymal brain lymphoma. Each patient underwent planar and single photon emission computed tomography imaging at 3-5 and 18-24 hours after administration of Lymphoscan. Scintigraphic results were compared with results of conventional diagnostic modalities. RESULTS: Overall, the sensitivity of Lymphoscan was 92% and the specificity was 86%. In brain lesions, there was 100% sensitivity and 100% specificity. Lymphoscan also had 100% sensitivity for sites of lymphomatous lymphadenopathy and for liver involvement. Although less specific in extracranial sites, Lymphoscan was correctly negative in sites of coexisting adenocarcinoma and pneumonia. Two patients had both parenchymal CNS and systemic lymphoma proven by biopsy. CONCLUSIONS: Lymphoscan appears to be a sensitive and specific method for diagnosing CNS lymphoma in AIDS patients. Although slightly less specific in extracranial sites, it may be helpful in differentiating lymphoma from other etiologies in these patients at risk for multiple neoplasms and opportunistic infections.

Adult↗
PubMed1997

Dosimetry of fractionated administration of 125I-labeled antibody at experimental radioimmunotargeting.

BACKGROUND: Radiotherapy of solid tumors is preferably performed in fractionated doses. Conversely, radioimmunotherapy with nuclide-carrying antibodies delivers a continuously decreasing low dose rate during a longer time period after a single injection. In the current study, the same total amount of 125I-labeled anticytokeratin monoclonal antibody (MoAb) was administrated in one, three, or ten injections and the dosimetry was evaluated. METHODS: Three groups of nude mice (10 mice each) with HeLa Hep 2 xenografts were injected with 1 x 100 microg/22.2 megabecquerel (MBq), 3 x 33 microg/7.4 MBq, and 10 x 10 microg/2.22 MBq 125I-labeled TS1 MoAb, respectively. The mice were examined scintigraphically over a 54-day period (total number of radio immunoscintigraphies (RISs) = approximately 700) and doses to tumor and normal tissues were estimated according to the medical internal radiation dose formalism. RESULTS: A single bolus injection caused higher tumor uptake, tumor dose, and tumor to nontumor dose ratio than administration of the same total dose of antibody and radioactivity in three or ten separate injections. The single bolus injection caused a tenfold higher tumor uptake (% injected dose, or ID) compared with the group receiving ten injections. This caused a tumor dose of 17 gray to the group receiving a single bolus injection. CONCLUSIONS: In this antigen target system, a single injection of a large amount of antibody was found to be more efficient than the same antibody dose subdivided into three or ten fractions. It was concluded that not only the radioactivity but also the amount of antibody per fraction should be considered when determining optimal fractionated radioimmunotherapy.

Animals↗