Summary
We describe the in vivo localization of radiolabeled mAb J28, a murine monoclonal antibody characterizing the oncodevelopmental human fetoacinar pancreatic (FAP) protein, at different stages of chemical induction of pancreatic tumors in the Syrian golden hamster. Before doing localization studies in this model, we looked at the cross-reactivity of mAb J28. Semiquantitative dot-blot analysis demonstrated that the antigen recognized in hamster pancreas has an oncodevelopmental expression pattern, while a molecular mass identical to that of human FAP was deduced from sodium dodecyl sulfate/polyacrylamide gel electrophoresis/nitrocellulose immunoblot.125I-labeled mAb J28 was administrated through micro-osmotic pumps to hamsters treated withN-nitrosobis(2-hydroxypropyl)amine (BHP). This was done at three intervals that roughly correspond to the latent period, pretumoral stages, and terminal cancerogenesis in two independent groups of hamsters. Both studies allowed similar results: (a) mAb J28 accumulated almost specifically in the pancreas; (b) maximal accumulation was associated with pleomorphic alterations of the acinar cell tissue at pretumoral stages; (c) no accumulation was found in the case of adenocarcinoma of the pancreas. It is concluded that FAP behaves as a marker of preneoplastic lesions, and therefore that radioimmunoimaging with mAb J 28 might help with early diagnosis of pancreatic cancer.
Similar content being viewed by others
Abbreviations
- BHP:
-
N-nitrosobis(2-hydroxypropyl)amine
- FAP:
-
protein fetoacinar pancreatic protein
- PBS:
-
phosphate-buffered saline
- SDS-PAGE:
-
sodium dodecyl sulfate/polyacrylamide gel electrophoresis
- BOP:
-
N-nitrosobis(2-oxopropyl)amine
References
Albers GHR, Escribano MJ (1986) A monoclonal antibody recognizing a concanavalin A reactive fetoacinar and cancer associated protein. Tumor Biol 7:252
Albers GHR, Escribano MJ, Gonzalez M, Mulliez N, Nap M (1987) The fetoacinar protein in the developing human pancreas. Differentiation 34:210–215
Albers GHR, Escribano MJ, Daher N, Nap M (1990) FAP protein in the normal pancreas, chronic pancreatitis, pancreatic adenocarcinoma and intra-abdominal metastasis of adenocarcinomas. An immunological study. Am J Clin Pathol 93:14–20
Bax J, Pour PM, Nagel DL, Lawson TA, Woutersen RA, Scherer E (1990) Long-term persistence of DNA alkylation in hamster tissues afterN-nitrosobis(2-oxopropyl)amine. J Cancer Res Clin Oncol 116:149–155
Benedi VJ, Escribano MJ, Zunghidau J, Burtin P (1984) Fetal pancreatic antigens in the Syrian golden hamster and their relation-ship to the development and carcenogenesis. Cancer Res 44:1135–1141
Cappelare P (1990) Editorial. Bull Cancer 77:25
Carrasquillo JA, Burin PA, Keenan AM, Reynolds JC, Schroff RW, Kenneth AF, Hsu SM, Gazdar AF, Mulshine JL, Oldham RK, Perentesis P, Horowitz M, Eddy J, James P, Larson SM (1986) Radioimmunodetection of cuataneous T-cell Lymphoma with 111-indium labeled T101 monoclonal antibody. N Engl J Med 315:673–680
Carré-Llopis A, Loridon-Rosa B, Escribano MJ (1987) Ultrastructual changes in acinar cells of hamster pancreas in chemically induced carcinogenesis. Cell Biol Int Rep 11:665–669
Delalaye B, Bischoff-Delalaye A, Buchegger F, Fliedner V, Grob JP, Volant JC, Pettavel J, Mach JP (1986) Detection of colorectal carcinoma by emission-computerized tomography after injection of125I-labeled Fab or F(ab)'2 fragments from monoclonal anticarcinoembryonic antigen antibodies. J Clin Invest 77:301–311
Diwakar J, Avijit L, Edward BR (1990) Immunoscintigraphy for detecting acute myocardial infarction without electrocardiographic changes. Br Med J 300:151–153
Eriguchi M, Carré-Llopis A, Orbach-Arbouys S, Escribano MJ (1987) Evolution of the expression of fetal acinar antigens during carcinogenesis of the pancreas in hamsters: individual follow-up by open biopsy. JNCI 78:519–525
Escribano MJ, Imperial S (1989) Purification and molecular characterization of FAP, a feto-acinar protein associated with the differentiation of human pancreas. J Biol Chem 264:21865–21871
Escribano MJ, Carré-Llopis A, Loridon-Rosa B (1985) Expression of oncofetal pancreatic antigens in hamster adult pancreas during experimental carcinogenesis. Br J Cancer 51:187–193
Escribano MJ, Cordier J, Nap M, Ten Kate FJW, Burtin P (1986) Differentiation antigens in fetal human pancreas. Reexpression in cancer. Int J Cancer 38:155–160
Flaks B, Moore MA, Flaks A (1982) Ultrastructural analysis of pancreatic carcinogenesis: V. Changes in differentiation of acinar cells during chronic treatment withN-nitrosobis(2-hydroxypropyl)amine. Carcinogenesis 3:485–498
Fujii Y, Albers GHR, Carré-Llopis A, Escribano MJ (1987) The diagnostic value of the fetoacinar pancreatic (FAP) protein in cancer of the pancreas; a comparative study with CA19/9. Br J Cancer 56:495–500
Goldenberg DM (1990) Introduction to the second conference on radioimmunodetection and radioimmunotherapy of cancer. Cancer Res [Suppl] 50:778S-779S
Goldenberg DM, Kun EE, DeLand FH, Bennett S, Primus FJ (1980) Radioimmunodetection of cancer with radioactive antibodies to carcinoembryonic antigen. Cancer Res 40:2984–2992
Greenwood FC, Hunter WM, Glover JS (1963) The preparation of131I-labelled human growth hormone of high specific radioactivity. Biochem J 89:114–123
Imperial S, Escribano MJ (1988) Concanavalin A variants of the fetoacinar pancreatic protein in the developing human pancreas and other biological sources. Biochim Biophys Acta 967:25–33
Khaw BA, Scott J, Fallon JT, Cahill SL, Haber E, Homcy C (1982) Myocardial injury: quantitation by cell sorting initiated with antimyosin fluorescent spheres. Science 217:1050–1052
Laborda J, Douillard JY, Lizzio EF, Hoffman T (1990) Comparative pharmacokinetics of a murine monoclonal antibody to a rat colon tumor in rats and nude mice. Cancer Res [Suppl.] 50:873S-876S
Larson SM (1990) Clinical Radioimmunodetection, 1978–1988: Overview and suggestions for standardization of clinical trials. Cancer Res [Suppl.] 50:892S-898S
Mach JP, Chatal JF, Lumbroso JD, Buchegger F, Forni M, Ritschard J, Berche C, Douillard JY, Carrel S, Herlyn M (1983) Tumor localization in patients by radiolabeled monoclonal antibodies against colon carcinoma. Cancer Res 43:5593–5600
Mazo A, Fujii Y, Shimotake J, Escribano MJ (1991) Expression of FAP protein in the pancreatic human tumor cell line BxPC-3. Pancreas 6:37–45
Moore MA, Takahashi M, Ito N, Bannasch P (1983) Early lesions during pancreatic carcinogenesis induced in Syrian hamster by DHPN or DOPN. I. Histologic, histochemical and radioautographic findings. Carcinogenesis 4:431–437
Pimm MV, Clegg JA, Baldwin RW (1987) Biodistribution and tumour localization of radiolabelled monoclonal antibody during continuous infusion in nude mice with human tumour xenografts. Eur J Cancer Clin Oncol 23:521–527
Pour P, Krüger FW, Chem D, Althoff J, Cardesa A, Mohr U (1974) Cancer of the pancreas induced in the syrian golden hamster. Am J Pathol 76:349–358
Pour P, Althoff J, Takahashi M (1977) Early lesions of pancreatic ductal carcinoma in the hamster model. Am J Pathol 88:291–308
Pour P, Runge RG, Birt D, Gingell R, Lawson T, Nagel D, Wallcave L, Salmasi SZ (1981) Current knowledge of pancreatic carcinogenesis in the hamster and its relevance to the human disease. Cancer 47:1573–1587
Rao MS, Reddy J (1980) Histogenesis of pseudo-ductular changes induced in the pancreas of guinea pigs treated withN-methyl-N-nitrosourea. Carcinogenesis 1:1027–1037
Sands H (1990) Experimental studies of radioimmunodetection of cancer: an overview. Cancer Res [Suppl] 50:809S-813S
Scarpelli DG, Rao MS, Subbarao V (1983) Augmentation of carcinogenesis byN-nitrosobis(2-oxopropyl)amine administered during S phase of the cell cycle in regenerating hamster pancreas. Cancer Res 43:611–616
Scherer E, Bax J, Woutersen RA (1989) Pathogenic interrelationship of focal lesions, nodules, adenomas and carcinomas in the multistage evolution of azaserine-induced rat pancreas carcinogenesis. NATO ASI (Adv Study Inst)ser ser A Life Sci 159:pp. 41–54
Sfakianiakis G, Garty II, Serafin AN (1990) Radioantibodies for the diagnosis and treatment of cancer: radioimmunoimaging (RAI) and radioimmunotherapy (RAT). Cancer Invest 8:381–405
Takeda Y, Escribano MJ (1991) Effects of insulin and somatostatin on the growth and the colony formation of two human pancreatic cancer cell lines. J Cancer Res Clin Oncol 117:416–420
Taylor A, Milton W, Eyre H, Fu Ping Wu, Christian P, Alazraki N, Datz F, Unger MW (1987) Radioimmunodetection of human melanoma with indium-111 labeled monoclonal antibodies. NCI Monogr 3:25–31
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Takeda, Y., Miralles, F., Daher, N. et al. Radioimmunolocalization of the monoclonal antibody J28 in early transformation stages inN-nitrosobis(2-hydroxypropyl)amine-induced pancreatic tumors in the Syrian golden hamster. J Cancer Res Clin Oncol 118, 377–385 (1992). https://doi.org/10.1007/BF01294443
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01294443