Abstract
This report summarizes results from an initial clinical evaluation of radioimnumodetection (RAID) in patients with pancreatic cancer using murine monoclonal antibody Nd2, directed against mucins from pancreatic cancer.Nd2 (2 mg) was labeled with 111ln (2 mCi) and injected into 19 patients suspected of having pancreatic cancer. Planar scintigrams were taken 3 days post–infusion. As for final diagnoses after surgery, 14 cases were pancreatic cancer, and one case each was chronic pancreatitis, neurilem–moma, islet cell carcinoma, cholangioma, and apparent absence of suspected recurrent lesion of pancreatic cancer. Of 14– patients with pancreatic cancer, RAID was positive in 10 cases (71.4%). Cases other than pancreatic cancer were all negative, so the specificity was 100%. These results demonstrate that RAID using 111In–Nd2 can be useful in differentiating exocrine pancreatic cancer from benign conditions and other types of carcinomas in the pancreatoduodenal regions.
Keywords: Radioimmunodetection, Pancreatic cancer, Nd2, Indium
Full Text
The Full Text of this article is available as a PDF (614.9 KB).
REFERENCES
- 1. ) Levin , D. L. , Connely , R. R. and Devesa , S. S.Demographic characteristics of cancer of the pancreas: mortality, incidence, and survival . Cancer , 47 , 1456 – 1468 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Koprowski , H. , Steplewski , Z. , Mitchell , K. , Heylyn , M. , Heriyn , D. and Fuhrer , P.Colorectal carcinoma antigen detected by hybridoma antibodies . Somatic Cell Genet. , 5 , 957 – 972 ( 1979. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Chung , Y.‐S. , Ho , J.J.L. , Kim , Y.‐S. , Tanaka , H. , Nakata , B. , Hiura , A. , Motoyoshi , H. , Satake , K. and Umeyama , K , The detection of a pancreatic cancer associated antigen in the serum of cancer patients . Cancer , 60 , 1636 – 1643 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Ho , J. J. L. , Chung , Y.‐S. , Fujimoto , Y. , Bi , N. , Ryan , W. , Yuan , S. Z. , Byrd , J. C. and Kim , Y.‐S.Mucin like antigens in a human pancreatic cancer cell line identified by murine monoclonal antibodies SPan‐1and YPan‐1 . Cancer Res. , 48 , 3924 – 3931 ( 1988. ). [PubMed] [Google Scholar]
- 5. ) Metzgar , R. S. , Horowitz , M. J. and Lan , M. S.Antigens of humanpancreaticadenocarcinomacelldefinedby murine monoclonal antibodies . Cancer Res. , 42 , 601 – 608 ( 1982. ). [PubMed] [Google Scholar]
- 6. ) Paganuzzi , M. , Onetto , M. , Marroni , P. , Barone , D. , Conio , M. , Aste , H. and Pugliese , V.CA 19‐9 and CA 50 in benign and malignant pancreatic and biliary diseases . Cancer , 61 , 2100 – 2108 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Takahashi , H. , Wilson , B. , Ozturk , M. , Motte , P. , Strauss , W. , Isselbacher , K. J. and Wands , J. R.In vitro localization of human colon adenocarcinoma by monoclonal antibody binding to a highly expressed cell surface antigen . Cancer Res. , 48 , 6573 – 6579 ( 1988. ). [PubMed] [Google Scholar]
- 8. ) Camera , L. , Kinuya , S. , Pai , L.H. , Garmestani , K. , Brechbiel , M. W. , Gansow , O. A. , Paik , C. H. , Pastan , I. and Carrasquillo , J. A.Preclinical evaluation of 111'In‐labeled B3 monoclonal antibody: biodistribution and imaging studies in nude mice bearing human epidermoid carcinoma xenografts . Cancer Res. , 53 , 2834 – 2839 ( 1993. ). [PubMed] [Google Scholar]
- 9. ) Buchsbaum , D. , Loyd , R. , Juni , J. , Wollner , L , Brubaker , P. , Hanna , D. , Spicker , J. , Burns , F. , Steplewski , Z. , Colcher , D. , Schlom , J. , Buchegger , F. and Mach , J.‐P.Localization and imaging of radiolabeled monoclonal antibodies against colorectal carcinoma in tumor bearing nude mice . Cancer Res. , 48 , 4324 – 4333 ( 1988. ). [PubMed] [Google Scholar]
- 10. ) Worlock , A. J. , Zalutsky , M.R. and Metzgar , R. S.Radiolocalization of human pancreatic tumors in athymic mice by monoclonal antibody DU‐PAN 1 . Cancer Res. , 50 , 7246 – 7251 ( 1990. ). [PubMed] [Google Scholar]
- 11. ) Colapinto , E.V. , Humphrey , P. A. , Zalutsky , M.R. , Groothuis , D. R. , Friedman , H. S. , de Tribolet , N. , Carrel , S. and Bigner , D. D.Comparative localization of murine monoclonal antibody Me‐14F(ab')2 fragment and whole IgG2a inhuman glioma xenografts . Cancer Res. , 48 , 5701 – 5707 ( 1988. ). [PubMed] [Google Scholar]
- 12. ) Goldenberg , D. M. , Deland , F. , Kim , E. , Bennett , S. , Primus , F. J. , van Nagell , Jr. , Estes , N. , DeSimone , P. , and Rayburn , P.Use of radiolabeled antibodies to carcinoem‐bryonic antigen for the detection and localization of diverse cancers by external photoscanning . N. Engl. J. Med. , 298 , 1384 – 1388 ( 1978. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Ishii , N. , Nakata , K. , Muro , T. , Furukawa , R. , Kono , K. , Kusumoto , Y. , Munehisa , T. , Koji , T. , Nagataki , S. , Nishi , S. , Tsukada , Y. and Hirai , H.Radioimmunodetection of cancer using antibodies to α‐fetoprotein and carcinoem‐bryonic antigen . Ann. NY Acad. Sci. , 417 , 270 – 276 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Krishnamurthy , S. , Morris , J. F. , Antonovic , R. , Ahmed , A. , Galey , W. T. , Duncan , C. and Krishnamurthy , G. T.Evaluation of primary lung cancer with Indium‐Ill anti‐carcinoembryonic antigen (Type ZCE‐025) monoclonal antibody scintigraphy . Cancer , 65 , 458 – 465 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Winzelberg , G. G. , Grossman , S. J. , Rizk , S. , Joyce , J. M. , Hill , J. B. , Atkinson , D. P. , Sudina , K. , Anderson , K. , McElwain , D. and Jones , A. M.Indium‐Ill monoclonal antibody B72.3 scintigraphy in colorectal cancer ‐ correlation with computed tomography, surgery, histopathol‐ogy, immunohistology, andhumanimmuneresponse . Cancer , 69 , 1656 – 1663 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Carrasquillo , J. A. , Sugarbaker , P. , Colcher , D. , Reynolds , J. C. , Esteban , J. , Bryant , G. , Perentesis , P. , Yokoyama , K. , Rotman , M. , Schlom , J. and Larson , S. M.Peritoneal carcinomatosis: imaging with intraperitoneal injection of I‐131‐labeled B72.3 monoclonal antibody . Radiology , 167 , 35 – 40 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Larson , S. M. , Divgi , C. R. and Scott , A. M.Overview of clinical radioimmunodetection of human tumors . Cancer , 73 , 832 – 835 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 18. ) McKearn , T. J.Radioimmunodetection of solid tumors: future horizons and application for radioimmunotherapy . Cancer , 71 , 4302 – 4313 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Sharkey , R. M. , Goldenberg , D. M. , Murthy , S. , Pinsky , H. , Vagg , R. , Pawlyk , D. , Siegel , J. A. , Wong , G. Y. , Gascon , P. , Izon , D. O. , Vezza , M. , Burger , K. , Swayne , L. C. , Pinsky , C. M. and Hansen , H. J.Clinical evaluation of tumor targeting with a high affinity, anti‐carcinoembry‐onic antigen specific, murine monoclonal antibody, MN‐14 . Cancer , 71 , 2082 – 2096 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 20. ) Sharkey , R. M. , Goldenberg , D. M. , Vagg , R. , Pawlyk , D. , Wong , G. Y. , Siegel , J. A. , Murthy , S. , Levine , G. M. , Izon , D. , Gascon , P. , Burger , K. , Swayne , L. C. and Hansen , H. J.Phase I clinical evaluation of a new murine monoclonal antibody (Mu‐9) against colon specific anti‐gen‐p for targeting gastrointestinal carcinomas . Cancer , 73 , 864 – 877 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 21. ) Maguire , R. T. , Pascucci , V. L. , Maroli , A. N. and Gulfo , J. V.Immunoscintigraphy in patients with colorectal, ovarian, and prostate cancer ‐ results with site specific immunoconjugates . Cancer , 72 , 3453 – 3462 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 22. ) Gallinger , S. , Reilly , R. M. , Kirsh , J. C. , Odze , R. D. , Schmocker , B. J. , Hay , K. , Polihronis , J. , Damani , M. T. , Shpitz , B. and Stern , H. S.Comparative dual label study of first and second generation antitumor‐associated glyco‐protein‐72 monoclonal antibodies in colorectal cancer patients . Cancer Res. , 53 , 271 – 278 ( 1993. ). [PubMed] [Google Scholar]
- 23. ) Nabi , H. A. and Doerr , R. J.Radiolabeled monoclonal antibody imaging (immunoscintigraphy) of colorectal cancers: current status and future perspective . Am. J. Surg. , 163 , 448 – 456 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 24. ) Klapdor , R. and Montz , R.Radioimmunodiagnosis of pancreatic cancer disease . Int. J. Pancreatol , 9 , 99 – 111 ( 1991. ). [PubMed] [Google Scholar]
- 25. ) Abdel‐Nabi , H. H. , Schwartz , A. N. , Wechter , D. G. , Higano , C. S. , Ortman‐Nabi , J. A. and Linger , M. W.Scintigraphic detection of gastric and pancreatic carcinomas with In‐111 ZCE025 monoclonal antibody . World J. Surg. , 15 , 122 – 127 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 26. ) Ho , J. J. L. , Bi , N. , Yan , P. S. , Norton , K. A. and Kim , Y. S.Characterization of new pancreatic cancer reactive monoclonal antibodies directed against purified mucin . Cancer Res. , 51 , 372 – 380 ( 1991. ). [PubMed] [Google Scholar]
- 27. ) Chung , Y. S. , Sawada , T. , Kondo , Y. , Ho , J. J. L. , Kim , Y. S. and Sowa , M.Tumor localization and biodistribu‐tion with radiolabeled monoclonal antibody against pancreatic cancer in tumor‐bearing nude mice . Tohoku J. Exp. Med. , 168 , 397 – 401 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 28. ) Hsu , S. M. , Raine , L. and Fanger , H.Use of avidin‐biotin‐peroxidase complex (ABC) in immunoperoxidase techniques . J. Histochem. Cytochetn. , 29 , 577 – 580 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 29. ) Goldenberg , D. M.Imaging and therapy of gastrointestinalcancerswithradiolabeledantibodies . AmJ. Gastraenterol , 86 , 1392 – 1403 ( 1991. ). [Google Scholar]
- 30. ) Tsuchiya , R. , Tomioka , T. , Izawa , K. , Noda , T. , Yamamoto , K. , Tsunoda , T. , Harada , N. , Yamaguchi , T. , Yoshino , R. , Miyamoto , T. and Eto , T.Collective review of small carcinomas of the pancreas . Ann. Surg. , 203 , 77 – 81 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. ) Pimm , M. V. , Durrent , L. G. and Baldwin , R. W.Influence of circulating antigen on the biodistribution and tumor localization of radiolabelled monoclonal antibody in a human tumour: nude mouse xenograft model . Eur. J. Cancer Clin. Oncol , 23 , 1325 – 1332 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 32. ) Hnatowich , D. J. , Rusckowski , M. , Brill , A. B. , Siebecker , D. A. , Misra , H. , Mardirossian , G. , Bushe , H. , Rescigno , A. , Stevens , S. , Johnson , D. K. and Griffin , T. W.Phar‐macokinetics in patients of an anti‐carcinoembryonic antigen antibody radiolabeled with indium‐111 using a novel diethylenetriammepentaacetic acid chelator . Cancer Res. , 50 , 7272 – 7278 ( 1990. ). [PubMed] [Google Scholar]
- 33. ) Beatty , B. G. , Beatty , J. D. , Williams , L. E. , Paxton , R. J. , Shively , J. E. and O'Connor‐Tressel , M.Effect of specific antibody pretreatment on liver uptake of' 111In‐labeled anti‐carcinoembryonic antigen monoclonal antibody in nude mice bearing human colon cancer xenografts . Cancer Res. , 49 , 1587 – 1594 ( 1989. ). [PubMed] [Google Scholar]
- 34. ) Buraggi , G. , Callegaro , L. , Turrin , A. , Gennari , L. , Bombardieri , E. , Mariani , G. , Deleide , G. , Dovis , M. , Gasparini , M. and Doci , R.Immunoscintigraphy of colorectal carcinoma with F(ab')2 fragment of anti‐CEA monoclonal antibody . Cancer Detect. Prev. , 10 , 335 – 345 ( 1987. ). [PubMed] [Google Scholar]
- 35. ) Kramer , E. L. , Sanger , J. J. , Walsh , C. , Kanamuller , H. , Unger , M. W. and Halverson , C.Contribution of SPECT to imaging of gastrointestinal adenocarcinoma with '“In‐labeled anti‐CEA monoclonal antibody . Am. J. Radiol. , 151 , 697 – 703 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 36. ) Bares , R. , Pass , J. , Truong , S. , Buell , U. and Schumpelick , V.Radioimmunoscintigraphy with 111In labelled monoclonal antibody fragment F(ab')2 BW431/319 against CEA: radiolabelling, antibody kinetics and distribution findings in tumour and nontumour patients . Nucl. Med. Commun. , 10 , 627 – 641 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 37. ) Carrasquillo , J. A. , Sugarbaker , P. , Colcher , D. , Reynolds , J. C. , Esteban , J. , Bryant , G. , Keenan , A. M. , Perentesis , P. , Yokoyama , K. , Simpson , D. E. , Ferroni , P. , Farkas , R. , Schlom , J. and Larson , S. M.Radioimmunoscintigraphy of colon cancer with iodine‐131‐labeled B73.3 monoclonal antibody . J. Nucl. Med. 29 , 1022 – 1030 ( 1988. ). [PubMed] [Google Scholar]
- 38. ) Colcher , D. , Milenic , D. E. , Ferroni , P. , Carrasquillo , J. A. , Reynolds , J. C. , Roselli , M. , Larson , S. M. and Schlom , J.In vivo fate of monoclonal antibody B72.3 in patients with colorectal cancer . J. Nucl. Med. , 31 , 1133 – 1142 ( 1990. ). [PubMed] [Google Scholar]
- 39. ) Stewart , J. S. W. , Hird , V. and Snook , D.Intraperitoneal radioimmunotherapy forovarian cancer:pharmacoki‐netics, toxicity and efficacy of 1‐131 labelled monoclonal antibodies . Int. J. Radiat. Oncol. Biol. Phys. , 16 , 405 – 413 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 40. ) Boulianne , G. L. , Hozumi , N. and Schulman , M. J.Production of functional chimeric mouse/human antibody . Nature , 312 , 643 – 646 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 41. ) Morrison , S. L. , Johnson , M. J. , Herzenberg , L. A. and Oi , V. T.Chimeric human antibody molecules: mouse antigen‐binding domains with human constant region domains . Proc. Natl. Acad. Sci. USA , 81 , 6851 – 6855 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42. ) Hosono , M. , Endo , K. , Sakahara , H. , Watanabe , Y. , Saga , T. , Nakai , T. , Kawai , C. , Matsumori , A. , Yamada , T. , Watanabe , T. and Konishi , J.Human/mouse chimeric antibodies show low reactivity with human anti‐murine antibodies (HAMA) . Br. J. Cancer , 65 , 197 – 200 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43. ) Hirayama , K. , Chung , Y. S. , Sawada , T. , Kim , Y. S. and Sowa , M.Characterizationandbiodistributionof a mouse/human chimeric antibody directed against pancreatic cancer mucin . Cancer ( Suppl. ), 75 , 1545 – 1553 ( 1995. ). [DOI] [PubMed] [Google Scholar]
- 44. ) Inui , A. , Chung , Y.‐S. , Sawada , T. , Kondo , Y. , Ho , J. J. L. , Kim , Y.‐S. and Sowa , M.Radioimmunotherapy for pancreatic carcinoma using 131I‐labeled monoclonal antibody Nd2 in xenografted nude mice . Jpn. J. Cancer Res. , 87 , 977 – 984 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]