Monoclonal HMFG2 Research Articles

Nuclear localization of MUC1 extracellular domain in breast, head and neck, and colon cancer.

The glycoprotein MUC1 is overexpressed and underglycosylated in cancer cells. MUC1 is translated as a single polypeptide that undergoes autocleavage into 2 subunits (the extracellular domain and the cytoplasmic tail), and forms a stable heterodimer at the apical membrane of normal epithelial cells. The MUC1 cytoplasmic tail localizes to the cytoplasm of transformed cells and is targeted to the nucleus. To study the expression of the MUC1 extracellular subunit in cell nuclei of neoplastic breast, head and neck, and colon samples. 330 primary tumor samples were analyzed: 166 invasive breast carcinomas, 127 head and neck tumors, and 47 colon tumors; 10 benign breast disease (BBD) and 40 normal specimens were also included. A standard immunohistochemical method with antigen retrieval was performed. Nuclear fractions from tissue homogenates and breast cancer cell lines (ZR-75, MDA-MB-231, MCF7, and T47D) were obtained and analyzed by Western blotting (WB). The anti-MUC1 extracellular subunit monoclonal antibody HMFG1 was used for immunohistochemistry. 37/166 breast cancer specimens, 5/127 head and neck cancer specimens, 2/47 colon cancer samples, and 3/10 BBD samples showed immunohistochemical staining at the nuclear level. No nuclear reaction was detected in normal samples. By WB, breast and colon cancer purified nuclear fractions showed reactivity at 200 kDa in 3/30 breast and 3/20 colon cancer samples as well as purified nuclear fractions obtained from breast cancer cell lines. This study shows that the MUC1 extracellular domain might be translocated to the cell nucleus in breast, head and neck, and colon cancer as well as BBD.

MUC‐1 mucin in normal human salivary glands detected by HMFG‐1 and HMFG‐2 monoclonal antibodies

The aim of this study was to determine the immunoexpression of normal salivary gland cells using two human milk fat globule membrane protein antibodies (HMFG-1 and HMFG-2). Paraffin-embedded, 5 microm-thick slides from parotid and submandibular gland tissues were cut and immunostained with monoclonal antibodies HMFG-1 and HMFG-2 against MUC1 protein. HMFG antigens were found in secretory epithelial cells and ductal cells lining the striated and intercalated ducts in the intraductal secretion material, and sometimes in the myoepithelial cells. Our results suggest that HMFG-1 and HMFG-2 proteins may play a role in normal salivary gland function, mainly in the manufacturing and secretion of saliva.

Extraperitoneal Leakage as a Possible Explanation for Failure of One-Time Intraperitoneal Treatment in Ovarian Cancer

We conducted a single-arm study to determine the biodistribution of intraperitoneally (i.p.) administered 90yttrium-labeled murine monoclonal antibody HMFG1 (90Y-muHMFG1) in patients with advanced stage ovarian cancer. Seventeen (17) patients in complete clinical remission for epithelial ovarian cancer were included. After completion of chemotherapy, a mixture of 111indium-labeled muHMFG1 (imaging) and 90Y-muHMFG1 (therapy) was i.p. administered by a surgically placed, indwelling i.p. catheter. Planar and single-photon emission computed tomography images were recorded to determine the distribution of the study medication during the first 6 days postinjection. Of the first 3 patients, 2 patients had extraperitoneal leakage of up to 50% of the injected dose within 24 hours after injection of the study medication. Extraperitoneal leakage was mainly seen in the retroperitoneal spaces covering the upper and lower quadrant of the abdomen. After adjustments in the procedure, leakage was observed in 2 of the remaining 14 patients. Extraperitoneal leakage of i.p. administered therapy does occur. Such leakage would reduce the locally delivered dose of a drug and could potentially have a negative impact on therapeutic efficacy. Given the potential attraction of developing i.p. treatments for intra-abdominal cancer, the observations in this study need to be taken into consideration.

Decreased intraperitoneal disease recurrence in epithelial ovarian cancer patients receiving intraperitoneal consolidation treatment with yttrium‐90‐labeled murine HMFG1 without improvement in overall survival

This study analyzes the site of disease recurrence in ovarian cancer patients to assess the influence of a single intraperitoneal (IP) administration of yttrium-90-labeled murine monoclonal antibody HMFG1 ((90)Y-muHMFG1) on the pattern of disease recurrence. In a large phase III trial ovarian cancer patients in complete clinical remission with FIGO stage Ic-IV were randomized between standard treatment plus a single IP (90)Y-labeled muHMFG1 versus standard treatment alone after negative second-look laparoscopy. Case report forms of all patients with disease recurrence were reviewed to determine site and date of recurrent disease. In total 447 patients were included in the study with a median follow-up of 3.5 years. Relapse was seen in 104/224 in the active and 98/223 in the control arm. Significantly fewer IP (p < 0.05) and more extraperitoneal (p < 0.05) relapses occurred in the active treatment arm. Time to IP recurrence was significantly longer (p = 0.0019) and time to extraperitoneal recurrence was significantly shorter for the active treatment arm (p < 0.001). The impact of IP radioimmunotherapy on IP relapse-free survival could only be seen in the subgroup of patients with residual disease after primary surgery (HR, 0.31; 95% CI, 0.18 to 0.53; p = 0.002). Although, there is no survival benefit for IP radioimmunotherapy as consolidation treatment for epithelial ovarian cancer, we found an improved control of IP disease, that was offset by increased extraperitoneal recurrences.

Mucin Characteristics of Human Corneal-Limbal Epithelial Cells that Exclude the Rose Bengal Anionic Dye

Rose bengal is an organic anionic dye used to assess damage of the ocular surface epithelium in ocular surface disease. It has been proposed that mucins have a protective role, preventing rose bengal staining of normal ocular surface epithelial cells. The current study was undertaken to evaluate rose bengal staining in a human corneal-limbal epithelial (HCLE) cell line known to produce and glycosylate membrane-associated mucins. HCLE cells were grown to confluence in serum-free medium and switched to DMEM/F12 with 10% serum to promote differentiation. Immunolocalization of the membrane-associated mucins MUC1 and MUC16 and the T-antigen carbohydrate epitope was performed with the monoclonal antibodies HMFG-2 and OC125 and jacalin lectin, respectively. To assess dye uptake, cultures were incubated for 5 minutes with 0.1% rose bengal and photographed. To determine whether exclusion of negatively charged rose bengal requires a negative charge at the cell surface, cells were incubated with fluoresceinated cationized ferritin. The effect of hyperosmotic stress on rose bengal staining in vitro was evaluated by increasing the ion concentration (Ca+2 and Mg+2) in the rose bengal uptake assay. The cytoplasm and nucleus of confluent HCLE cells cultured in media without serum, lacking the expression of MUC16 but not MUC1, as well as human corneal fibroblasts, which do not express mucins, stained with rose bengal. Culture of HCLE cells in medium containing serum resulted in the formation of islands of stratified cells that excluded rose bengal. Apical cells of the stratified islands produced MUC16 and the T-antigen carbohydrate epitope on their apical surfaces. Colocalization experiments demonstrated that fluoresceinated cationized ferritin did not bind to these stratified cells, indicating that rose bengal is excluded from cells that lack negative charges. Increasing the amounts of divalent cations in the media reduced the cellular area protected against rose bengal uptake. These results indicate that stratification and differentiation of corneal epithelial cells, as measured by the capacity to produce the membrane-associated mucin MUC16 and the mucin-associated T-antigen carbohydrate on their apical surfaces provide protection against rose bengal penetrance in vitro and suggest a role for membrane-associated mucins and their oligosaccharides in the protection of ocular surface epithelia.

Intraperitoneal radioimmunotherapy in an ovarian carcinoma mouse model: Effect of the radionuclide

Despite debulking surgery and multidrug chemotherapy, advanced stage ovarian cancer has a high mortality rate. Radioimmunotherapy (RIT) is a treatment modality using specific, radiolabeled antibodies that guide cytotoxic radionuclides to cancer cells. In the present study, the therapeutic efficacy of RIT with murine monoclonal antibody HMFG1 labeled with three different beta-radiation emitting radionuclides (90Yttrium, 186Rhenium, and 131Iodine) was assessed in athymic BALB/c mice with intraperitoneally growing NIH:OVCAR-3 ovarian carcinoma xenografts. Each of the three intraperitoneally administered radiolabeled antibody preparations (90Y-HMFG1, 186Re-HMFG1, and 131I-HMFG1) caused a significant delay in ascites formation and mortality as compared to the control groups treated with 90Y-labeled irrelevant antibody, nonradiolabeled HMFG1, or phosphate buffered saline. Intraperitoneally (ip) administered 90Y-HMFG1 was shown to have a significantly higher abdominal retention as compared to the intraperitoneally administered irrelevant antibody 90Y-G250. Furthermore, intraperitoneally administered 90Y-HMFG1 more effectively inhibited tumor growth than intravenously administered 90Y-HMFG1. It was concluded that in intraperitoneally located malignant disease with ascitic cell clusters and tumor deposits, intraperitoneal administration of RIT seemed preferable as compared to intravenous administration. The choice of the most optimal radionuclide in intraperitoneally located malignancies needs further research, but could well depend on tumor characteristics such as the size of the tumor lesions.

Intraperitoneal radioimmunotherapy in an ovarian carcinoma mouse model: Effect of the radionuclide

Despite debulking surgery and multidrug chemotherapy, advanced stage ovarian cancer has a high mortality rate. Radioimmunotherapy (RIT) is a treatment modality using specific, radiolabeled antibodies that guide cytotoxic radionuclides to cancer cells. In the present study, the therapeutic efficacy of RIT with murine monoclonal antibody HMFG1 labeled with three different beta-radiation emitting radionuclides (90Yttrium,186Rhenium, and131Iodine) was assessed in athymic BALB/c mice with intraperitoneally growing NIH:OVCAR-3 ovarian carcinoma xenografts. Each of the three intraperitoneally administered radiolabeled antibody preparations (90Y-HMFG1,186Re-HMFG1, and131I-HMFG1) caused a significant delay in ascites formation and mortality as compared to the control groups treated with90Y-labeled irrelevant antibody, nonradiolabeled HMFG1, or phosphate buffered saline. Intraperitoneally (ip) administered90Y-HMFG1 was shown to have a significantly higher abdominal retention as compared to the intraperitoneally administered irrelevant antibody90Y-G250. Furthermore, intraperitoneally administered90Y-HMFG1 more effectively inhibited tumor growth than intravenously administered 90Y-HMFG1. It was concluded that in intraperitoneally located malignant disease with ascitic cell clusters and tumor deposits, intraperitoneal administration of RIT seemed preferable as compared to intravenous administration. The choice of the most optimal radionuclide in intraperitoneally located malignancies needs further research, but could well depend on tumor characteristics such as the size of the tumor lesions.

MUC1 in normal and impaired spermatogenesis.

The MUC1 mucin [also known as episialin, epithelial membrane antigen (EMA) or polymorphic epithelial mucin (PEM)] is a component of the mucosal glycocalyx, contributing to anti-adhesive and protective cell functions. MUC1 has been shown in a variety of epithelial cell types in the reproductive tracts of males and females, but this is the first report of its expression in human testis and non-epithelial cells of the germ cell lineage. Analysing 65 testes with normal or impaired spermatogenesis, we identified MUC1 protein in maturing germ cells by immunohistochemistry using the monoclonal antibodies HMFG1, HMFG2 and SM3 binding to different glycosylation variants. MUC1 expression was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis on tissue extracts of human testis, and RT-PCR of selected germ cells after UV laser-assisted cell picking. MUC1 glycosylation variants were selectively distributed during normal spermatogenesis. Whereas HMFG1 labelled certain groups of pachytene spermatocytes, HMFG2 labelled only spermatids. Low glycosylated forms of MUC1 mucin, recognized by SM3, were not found. In contrast to its weak expression during normal spermatogenesis, the HMFG1 glycosylation variant accumulated markedly in all spermatocytes showing abnormal or arrested maturation. These results suggest a variable glycosylation of MUC1 mucin in differentiating germ cells, which is aberrant in pathological conditions.

A transgenic mouse model for tumour immunotherapy: induction of an anti-idiotype response to human MUC1.

MUC1 is a membrane bound, polymorphic epithelial mucin expressed at the luminal surface of glandular epithelium. It is highly expressed in an underglycosylated form on carcinomas and metastatic lesions and is, therefore, a potential target for immunotherapy of cancer. The monoclonal antibody HMFG1 binds the linear core protein sequence, PDTR, contained within the immunodominant domain of the tandem repeat of MUC1. The efficacy of murine and humanized HMFG1 (Ab1) used as an anti-idiotypic vaccine was examined in mice transgenic for human MUC1 (MUC1.Tg) challenged with murine epithelial tumour cells transfected with human MUC1. Humoral idiotypic cascade through Ab2 and Ab3 antibodies was observed in MUC1.Tg mice following multiple antibody inoculations in the presence of adjuvant. Impaired tumour growth at day 35 and highest Ab3 levels were found in mice that had received mHMFG1 with RAS adjuvant. However, comparison of Ab3 levels in individual mice with tumour size in all treatment groups did not show a correlation between smaller tumours and increased levels of anti-idiotype antibody. This suggests that the anti-tumour effects of anti-idiotype vaccination are not solely related to the induction of idiotypic antibody cascades and probably involve other mechanisms. © 2000 Cancer Research Campaign

Synthesis and antibody recognition of mucin 1 (MUC1)-alpha-conotoxin chimera.

We synthesized and characterized new chimera peptides by inserting an epitope of the mucin 1 glycoprotein (MUC1) as a 'guest' sequence in the 'host' structure of alpha-conotoxin GI, a 13-residue peptide (ECCNPACGRHYSC) isolated from the venom of Conus geographus. The Pro-Asp-Thr-Arg (PDTR) sequence of MUC1 selected for these studies is highly hydrophilic and adopts a beta-turn conformation. The alpha-conotoxin GI also contains a beta-turn in the 8-12 region, which is stabilized by two disulphide bridges in positions 2-7 and 3-13. Thus, the tetramer sequence of alpha-conotoxin, Arg9-His-Tyr-Ser12, has been replaced by PDTR, comprising the minimal epitope for MUC1 specific monoclonal antibodies (MAbs) HMFG1 (PDTR) and HMFG2 (DTR). Synthesis of the chimera peptide was carried out by Fmoc strategy on (4-(2',4'-dimethoxyphenyl-aminomethyl)phenoxy) (Rink) resin and either 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) or air oxidation was applied for the formation of the first Cys3-Cys13 or Cys2-Cys7 disulphide bridge, respectively. For the second disulphide bridge, three different oxidation procedures (iodine in acetic acid, 10% DMSO/1 M HCl or tallium trifluoroacetate (Tl(tfa)3) in TFA) were utilized. The HPLC purified peptides were characterized by electrospray mass spectrometry (ES-MS) and amino acid analysis. The CD spectra of the bicyclic MUC1-alpha-[Tyr1]-conotoxin chimera peptide showed partially ordered conformation with turn character. In antibody binding studies, the RIA data showed that both the linear and the bicyclic forms of MUC1-alpha-[Tyr1]-conotoxin chimera were recognized by MAb HMFG1 specific for PDTR sequence, while no binding was observed between MAb HMFG2 and various forms of the chimera. MAb HMFG1, using synthetic epitope conjugates or native MUC1 as target antigens, recognizes the PDTR motif more efficiently in the linear than in the bicyclic compound, but no reactivity was found with the monocyclic forms of MUC1-alpha-[Tyr1]-conotoxin chimera, underlining the importance of certain conformers stabilized by double cyclization.

Synthesis and antibody recognition of mucin 1 (MUC1)-α-conotoxin chimera

We synthesized and characterized new chimera peptides by inserting an epitope of the mucin 1 glycoprotein (MUC1) as a ‘guest’ sequence in the ‘host’ structure of α-conotoxin GI, a 13-residue peptide (ECCNPACGRHYSC) isolated from the venom of Conus geographus. The Pro-Asp-Thr-Arg (PDTR) sequence of MUC1 selected for these studies is highly hydrophilic and adopts a β-turn conformation. The α-conotoxin GI also contains a β-turn in the 8–12 region, which is stabilized by two disulphide bridges in positions 2–7 and 3–13. Thus, the tetramer sequence of α-conotoxin, Arg9-His-Tyr-Ser12, has been replaced by PDTR, comprising the minimal epitope for MUC1 specific monoclonal antibodies (MAbs) HMFG1 (PDTR) and HMFG2 (DTR). Synthesis of the chimera peptide was carried out by Fmoc strategy on (4-(2′,4′-dimethoxyphenyl-aminomethyl)phenoxy) (Rink) resin and either 5,5′-dithio-bis-(2-nitrobenzoic acid) (DTNB) or air oxidation was applied for the formation of the first Cys3–Cys13 or Cys2–Cys7 disulphide bridge, respectively. For the second disulphide bridge, three different oxidation procedures (iodine in acetic acid, 10% DMSO/1 M HCl or tallium trifluoroacetate (Tl(tfa)3) in TFA) were utilized. The HPLC purified peptides were characterized by electrospray mass spectrometry (ES-MS) and amino acid analysis. The CD spectra of the bicyclic MUC1-α-[Tyr1]-conotoxin chimera peptide showed partially ordered conformation with turn character. In antibody binding studies, the RIA data showed that both the linear and the bicyclic forms of MUC1-α-[Tyr1]-conotoxin chimera were recognized by MAb HMFG1 specific for PDTR sequence, while no binding was observed between MAb HMFG2 and various forms of the chimera. MAb HMFG1, using synthetic epitope conjugates or native MUC1 as target antigens, recognizes the PDTR motif more efficiently in the linear than in the bicyclic compound, but no reactivity was found with the monocyclic forms of MUC1-α-[Tyr1]-conotoxin chimera, underlining the importance of certain conformers stabilized by double cyclization. Copyright © 2000 European Peptide Society and John Wiley & Sons, Ltd.

Long term survival of patients with advanced ovarian cancer treated with intraperitoneal radioimmunotherapy.

PURPOSE: To determine the long term survival of patients with advanced ovarian cancer treated with radioimmunotherapy following cytoreductive surgery and platinum based chemotherapy. PATIENTS AND METHODS: Eligibility criteria included patients with histological evidence of ovarian cancer stages IC-IV following completion of conventional platinum containing chemotherapy. Of 52 patients entered into the study, 31 had residual disease following standard chemotherapy and 21 patients had achieved complete remission. Treatment consisted of one intraperitoneal administration of 25 mg of monoclonal antibody HMFG1 labelled with 18 mCi/m2 of 90Y. Survival was the primary end-point. RESULTS: In the group of 21 patients who had achieved complete remission following surgery, conventional chemotherapy and intraperitoneal radioimmunotherapy, the median survival has not been reached with a maximum follow-up of 12 years. Survival at greater than 10 years is 78%. CONCLUSION: This study suggests that a substantial proportion of patients who achieve complete remission with conventional therapy can achieve a long-term survival benefit when treated with intraperitoneal radioimmunotherapy using HMFG1 labelled with 90Y.

Identification of parietal cells in gastric body mucosa with HMFG-2 monoclonal antibody.

To identify parietal cells in the upper gastrointestinal tract by an immunoperoxidase method, using commercially available monoclonal antibodies. Routine surgical biopsy specimens of gastric body mucosa were examined using the avidin-biotin peroxidase method with the monoclonal antibodies HMFG-1 and HMFG-2 to identify parietal cells. Double immunoperoxidase labelling with HK12.18, a well characterised monoclonal antibody directed against an epitope on the alpha (catalytic) subunit of H+ translocating, K+ stimulated adenosine triphosphatase (H,K-ATPase), was used to confirm that HMFG-1 and -2 stained parietal cells. HMFG-1 and HMFG-2 showed consistent parietal cell staining patterns in the gastric body mucosa. HMFG-2 gave a more intense staining pattern of the secretory canaliculi. This was confirmed by double immunolabelling with HK12.18. HMFG monoclonal antibodies are recommended as highly specific markers of human gastric parietal cells.

Characterisation of a recombinant Fv fragment of anti-MUC1 antibody HMFG1

A recombinant Fv (variable fragment) has been produced for the murine monoclonal antibody HMFG1. This antibody was raised against human milk fat globules and reacts with an epitope (PDTR) in the protein core of MUC1 mucins, which are up-regulated in human breast and other carcinomas. Binding specificity of the Fv fragment has been demonstrated through immunoaffinity purification, and by radioimmunoassay. The affinity constants for this Fv fragment and for the proteolytically produced Fab (antigen binding fragment) of the related humanised antibody HuHMFG1 were determined by monitoring the fluorescence quenching of the antibody fragments whilst adding aliquots of MUC1 related antigenic peptides KAPDTRPAPG and VTSAPDTRPAPG. Using these techniques it has been demonstrated that the products of these different methods of antibody fragmentation are comparable, and suitable for solution structure analysis using nuclear magnetic resonance (NMR) spectroscopy.

MODIFIED BETA-TURNS IN BREAST CARCINOMA-ASSOCIATED MUC1 RELATED PEPTIDES

The solution structure of two carcinoma-associated MUC1 core related peptides has been investigated by nuclear magnetic resonance (n.m.r.) spectroscopy. The peptide APDTRPAPG resembles previously studied MUC1 related peptides with a type I beta-turn identified in the region PDTR. This portion of the peptide has previously been identified as the binding site for the monoclonal antibodies HMFG-1 and HMFG-2. The peptide where the D has been replaced by its homologue E, which is selectively recognized by the antibody HMFG-1 but not HMFG-2, appears to have a modified tum region. While amide to amide through space connections are observed the results suggest a more open tum structure.

Reactivity of the high-M(r) mucin-like glycoproteins in human milk with monoclonal antibodies HMFG-1 and HMFG-2.

Journal Article Reactivity of the High-Mr Mucin-like Glycoproteins in Human Milk with Monoclonal Antibodies HMFG-1 and HMFG-2 Get access Yoshihiro Kanamaru, Yoshihiro Kanamaru Department of Food Science, Faculty of Agriculture, Gifu University, Gifu 501–11, Japan Search for other works by this author on: Oxford Academic Google Scholar Satoshi Nagaoka, Satoshi Nagaoka Department of Food Science, Faculty of Agriculture, Gifu University, Gifu 501–11, Japan Search for other works by this author on: Oxford Academic Google Scholar Yasuo Kuzuya, Yasuo Kuzuya Department of Food Science, Faculty of Agriculture, Gifu University, Gifu 501–11, Japan Search for other works by this author on: Oxford Academic Google Scholar Makoto Shimizu Makoto Shimizu Department of Food Science, Faculty of Agriculture, Gifu University, Gifu 501–11, JapanSchool of Food and Nutritional Sciences, The University of Shizuoka, Shizuoka 422, Japan Search for other works by this author on: Oxford Academic Google Scholar Bioscience, Biotechnology, and Biochemistry, Volume 57, Issue 6, 1 January 1993, Pages 1001–1003, https://doi.org/10.1271/bbb.57.1001 Published: 01 January 1993 Article history Received: 05 October 1992 Published: 01 January 1993

Expression of the human MUC1 mucin cDNA in a hamster pancreatic tumor cell line HP-1.

A full length cDNA for the human mucin gene, MUC1, under the control of human beta actin promoter, was transfected into a carcinogen induced hamster pancreatic ductal tumor cell line, HP-1. Transfectants were selected by resistance to geneticin. Integration of the foreign human MUC1 cDNA occurred at multiple sites in the genome of HP-1. Northern blot analysis showed MUC1 expression in cells transfected with MUC1 cDNA placed in the correct orientation, but not in control cells (HP-1 cells transfected with vector alone, or with the MUC1 cDNA placed in the antisense orientation). Western blot analysis using monoclonal antibody HMFG-2, which is reactive with the MUC1 protein, showed results consistent with the Northern blot data. Positive immunoperoxidase staining using HMFG-2 was seen in HP-1 cells transfected with MUC1 cDNA but not with untransfected or HP-1 control cells. The integration of human MUC1 mucin gene in HP-1 cells caused no significant change in the growth rate of HP-1 cells in vitro, but resulted in an enhanced growth rate for xenografts of MUC1 transfected HP-1 cells grown in nude mice.

The effect of immunophotodynamic therapy using the monoclonal antibody HMFG-1 linked to hematoporphyrin on MCF-7 cell in vitro.

The effect of immunophotodynamic therapy using the monoclonal antibody HMFG-1 linked to hematoporphyrin on MCF-7 cell in vitro.

Carcinomatous meningitis: antibody-guided therapy with I-131 HMFG1.

Seven patients with carcinomatous meningitis were administered intrathecal I-131 labelled monoclonal antibody HMFG1. Clinical responses were seen in two patients, with a long term survivor at 32 months. Aseptic meningitis occurred in 4/7 patients, but more serious toxicity was observed in the form of seizures (2/7 patients) and myelosuppression (3/7 patients). Partial obliteration of the subarachnoid space was identified as a potential problem in patients with advanced disease.

Radioimmunoscintigraphy of Orbital Metastases from Ovarian Carcinoma

Radioimmunoscintigraphy with I-123 labeled monoclonal antibody HMFG1 has been used for imaging primary and metastatic ovarian neoplasms. Uptake of I-123 labeled HMFG1 is reported in a patient with an orbital metastasis from a primary ovarian adenocarcinoma. Radioimmunoscintigraphy may have a role to play in imaging metastatic orbital neoplasms.