Abstract
The actual interest of immunoscintigraphy for the detection of liver tumours was investigated by both visual examination and quantitative analysis in 41 patients with hepatoma (HCC, 21 cases, 13 AFP-secreting), other primary or secondary liver cancer (9 cases), testicular cancer (2 cases) and cancer free cirrhosis (9 cases). All patients were injected with 123I-anti-alphafetoprotein (AFP) monoclonal antibodies (MAbs) and scans were performed after 28±2 h. In the hepatoma-bearing patients, 11 positive anti AFP scans were found; 9 of them had an enhanced serum; besides, 3 non HCC tumours were also detected. With respect to hepatoma diagnosis, sensitivity was 52.5% and specificity 66.5%. For all hepatomas, it was striking that the positivity rate was 2/10 and 9/11, respectively, when HCC was and was not associated with cirrhosis. Among 6 patients with a positive anti AFP scan who were also injected with control anti hCG 123I-MAb, 5 positive anti hCG scans were surprisingly found, with specificity indices ranging between 1.00 and 1.75. The quantitative study also highlighted the importance for hepatoma detection of specific and non specific factors such as serum AFP, tumoural vascularization, non tumoural liver uptake and intrahepatic distribution of HCC.
Anti AFP immunoscintigraphy appears as a poorly sensitive and moderately specific method for hepatoma diagnosis. In contrast, non tumoural liver uptake level could be more useful for discriminating HCC from liver metastases and perhaps to detect the early extension of HCC.
Similar content being viewed by others
References
Bassendine MF (1987) Aetiological factors in the hepatocellular cancer. In: Williams R, Johnson PJ (eds) Clinical Gastroenterology. Liver tumours. Baillière Tindall, London, Philadelphia, pp 1–16
Begent RHJ (1985) Recent advances in tumour imaging: use of radiolabelled antitumour antibodies. Biochem Biophys Acta 780:151–166
Bellet DH, Wands JR, Isselbacher KJ, Bohuon C (1984) Serum alpha-fetoprotein levels in human disease: perspective from a highly specific monoclonal radioimunoassay. Proc Natl Acad Sci USA 81:3869–3873
Bellet D, Ozturk M, Bidart JM, Bohuon C, Wands JR (1986) Sensitive and specific assay for human chorionic gonadotropin based on anti-peptide and anti-hCG monoclonal antibodies: construction and clinical implications. J Clin Endocrinol Metab 63:1319–1327
Bergmann JF, Lumbroso JD, Manil L, Saccavini JC, Rougier P, Assicot M, Mathieu A, Bellet D, Bohuon C (1987) Radiolabelled monoclonal antibodies against alpha-fetoprotein for in vivo localization of human hepatocellular carcinoma by immunotomoscintigraphy. Eur J Nucl Med 13:385–390
Bourguet P, Estable P, Herry JY (1985) Un traceur hépatobiliaire peut-il aider au diagnostic d'un hépatome? Exemple du Diethyl-IDA. J Biophys Biomec 9:241–243
Bradwell AR, Fairweather DS, Dykes PW, Keeling A, Vaughan A, Taylor J (1985) Limiting factors in the localization of tumours with radiolabelled antibodies. Immunol Today 6:163–170
Carlson RI, Ben-Porath E, Shouval D, Strauss W, Isselbacher KJ, Wands JR (1985) Antigenic characterization of human hepatocellular carcinoma: development of in vitro and in vivo immunoassays that use monoclonal antibodies. J Clin Invest 76:40–51
Constantinesco A, Lallot C (1984) Intérêt de l'analyse de Fourier pour les explorations dynamiques non périodiques en médecine nucléaire. J Biophys Med Nucl 8:251–257
DeLand FH, Goldenberg DM (1985) Diagnosis and treatment of neoplasms with radionuclide-labelled antibodies. Semin Nucl Med 15:2–11
Delaloye B, Bischof-Delaloye A, Buchegger F, Fliedner V von, Grob JP, Volant JC, Pettavel J, Mach JP (1986) Detection of colorectal carcinoma by emission-computerized tomography after injection of 123I-labelled Fab or F(ab')2 fragments from monoclonal anti-carcinoembryonic antigen antibodies. J Clin Invest 77:301–311
Demangeat JL, Constantinesco A, Brunot B, Foucher G, Farcot JM (1988) Three-phase bone scanning in reflex sympathetic dystrophy of the hand. J Nucl Med 29:26–32
Deugnier Y, Auffret P, Lehry D, Brissot P, Bourel M (1987) Marqueurs biologiques du carcinome hépatocellulaire. Gastroenterol Clin Biol 11:648–657
Goldenberg DM (1976) Oncofetal and other tumour-associated antigens of the human digestive system. Curr Top Pathol 63:289–342
Goldenberg DM, DeLand FH, Kim EE, Bennett S, Primus FJ, Van Nagell JR, Estes N, De Simone P, Rayburn P (1978) Use of radiolabelled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning. N Engl J Med 298:1384–1388
Goldenberg DM, Kim EE, DeLand FH, Spremulli E, Nelson MO, Gockermann JP, Primus FJ, Corgan RL, Alpert E (1980) Clinical studies on the radioimmunodetection of tumours containing alphafetoprotein. Cancer 45:2500–2505
Hunter WM, Greenwood FC (1962) Preparation of iodine-131-labelled human growth hormone of high specific radioactivity. Nature 194:495–496
Ishii N, Nakata K, Muro T, Furukawa R, Kono K, Kusumoto Y, Munehisa T, Koji T, Nagataki S, Nishi S, Tsukada Y, Hirai H (1983) Radioimmunodetection of cancer using antibodies to alphafetoprotein and CEA. Ann NY Acad Sci 417:270–276
Key ME, Bernhard MI, Hoyer LC, Foon KA, Oldham RK, Hanna MG (1983) Guinea-pig line 10 hepatocarcinoma model for monoclonal antibody serotherapy: in vivo localization of a monoclonal antibody in normal and malignant tissues. J Immunol 130:1451–1457
Kim EE, DeLand FH, Nelson MO, Bennett S, Simmons G, Alpert E, Goldenberg DM (1980) Radioimmunodetection of cancer with radiolabelled antibodies to alpha-fetoprotein. Cancer Res 40:3008–3012
Koji T, Ishii N, Munehisa T, Kusumoto Y, Nakamura S, Tamenishi A, Hara A, Kobayashi K, Tsukada Y, Nishi S, Hirai H (1980) Localization of radioiodinated antibody to alphafetoprotein in hepatoma transplanted in rats and a case report of alphafetoprotein antibody treatment of a hepatoma patient. Cancer Res 40:3013–3015
Lumbroso J, Bergmann JF, Manil L, Saccavini JC, Rougier P, Bellet D, Bohuon C, Parmentier C (1986) Double isotope emission tomography for detecting human hepatocellular carcinoma by immunoscintigraphy. In: 33rd Annual Meeting of the American Society of Nuclear Medicine. Washington, June 22–25, 1986, J Nucl Med 27:1022 (Abstr 595)
Manil L, Motte P, Pernas P, Troalen F, Bohuon C, Bellet D (1986a) Evaluation of protocols for purification of mouse monoclonal antibodies: yield and purity in two-dimensional gel electrophoresis. J Immunol Methods 90:25–37
Manil L, Roblot-Treupel L, Couvreur P (1986b) Isobutyl-cyanoacrylate nanoparticles as a solid phase for an efficient immunoradiometric assay. Biomaterials 7:212–216
Mann BD, Cohen MB, Saxton RE, Morton DL, Benedict WF, Korn EL, Spolter L, Graham LS, Chang CC, Burk MW (1984) Imaging of human tumour xenografts in nude mice with radiolabelled monoclonal antibodies. Limitations of specificity due to non-specific uptake of antibody. Cancer 54:1318–1327
Markham N, Ritson A, James O, Curtin N, Bassendine M, Sikora K (1986) Primary hepatocellular carcinoma localised by a radiolabelled monoclonal antibody. J Hepatology 2:25–31
Nakata K, Furukawa R, Kono K, Muro T, Sato A, Kusumoto Y, Ishii N, Munehisa T, Koji T, Nagataki S (1984) Tumor/serum ratios of alphafetoprotein and radioimmunolocalization of primary liver cancer. Tumor Biol 5:161–169
Nishi S, Yamazaki H, Hirai H, Ishii N, Koji T, Nagataki S (1982) Monoclonal antibodies against alphafetoprotein. In vitro and in vivo applications. In: Raynaud C (eds) Proceedings of the IIIrd World Congress of Nuclear Medicine and Biology. Pergamon Press, Paris, pp 2304–2307
Nose M, Wigzell H (1983) Biological significance of carbohydrate chains on monoclonal antibodies. Proc Natl Acad Sci USA 80:6632–6636
Price DC, Leibel SA, Van Raalte G, Neely M (1985) Patient survival compared with tumour antibody uptake in hepatoma patients treated with polyclonal I-131-labelled anti-ferritin antibodies, 10th Annual Western Regional Meeting, Palm Springs, Ca, October 17–20, 1985, Clin Nucl Med 10:22
Rabinowitz SA, McKusic KA, Strauss HW (1984) 99mTc-red blood cell scintigraphy in evaluating focal liver lesions. Am J Roentgenol 143:63–68
Shouval D, Eilat D, Carlson RI, Adler R, Livni N, Wands JR (1985) Human hepatoma-associated cell surface antigen: identification and characterization by means of monoclonal antibodies. Hepatology 5:347–356
Stockert RJ, Kressner MS, Collins JC, Sternlieb I, Morell AG (1982) IgA interaction with the asialoglycoprotein receptor. Proc Natl Acad Sci USA 79:6229–6231
Author information
Authors and Affiliations
Additional information
This work was partly supported by the ARC grant nr 6265
Rights and permissions
About this article
Cite this article
Demangeat, JL., Mamil, L., Demangeat, C. et al. Is anti-alphafetoprotein immunoscintigraphy a promising approach for the diagnosis of hepatoma?. Eur J Nucl Med 14, 612–620 (1988). https://doi.org/10.1007/BF00251785
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00251785