Abstract
The detection of chromogranins (Cg) by immunohistochemistry and serology represents a new in vitro diagnostic tool for endocrine tumours. We have recently reported on the feasibility of targeting chromogranin A (CgA) for in vivo detection of pituitary adenomas by immunoscintigraphy (ISG). The scintigraphic procedure, based on an anti-CgA monoclonal antibody and on the avidin-biotin three-step method (Cg-3S-ISG), was evaluated on a group of 29 consecutive patients with known or suspected endocrine tumours other than pituitary adenomas, i.e. medullary thyroid carcinoma, carcinoid, insulinoma and parathormone- or ACTH-producing tumours. Primary tumours (10) and recurrences (16) were visualised in 26 patients, whereas conventional imaging techniques (planar radiography, computerised tomography, magnetic resonance imaging and ultrasonography) failed to detect the tumour sites in ten of the same (Cg-3S-ISG-positive) patients. Therefore, these preliminary results indicate that Cg-3S-ISG, the first immunological method able to detect endocrine tumours in vivo, has a higher diagnostic accuracy than conventional imaging techniques (93.1% compared with 65.5%).
Similar content being viewed by others
Results
Deftos LJ. Chromogranin A: its role in endocrine function and as an endocrine and neuroendocrine tumor marker.Endocr Rev 1991; 12: 181–187.
Wincler H, Fischer-Colbrie R. The chromogranins A and B: the first 25 years and future perspectives.Neurosciences 1992; 49: 497–528.
Pelagi M, Bisiani C, Gini A, Bonardi MA, Rosa P, Marè P, Viale G, Cozzi MG, Salvadore M, Zanini A, Siccardi AG, Buffa R. Preparation and characterization of anti-human chromogranin A and chromogranin B (secretogranin I) monoclonal antibodies.Mol Cell Probes 1989; 3: 87–101.
Settleman J, Nolan J, Angeletti RH. Chromogranin, an integral membrane protein.J Biol Chem 1985; 260: 1641–1644.
Pimplikar S, Hutmer WB, Chromogranin B (secretogranin 1), a secretory protein of the regulated pathway, is also present in a tightly membrane-associated form in PC12 cells.J Biol Chem 1992; 267: 4110–4113.
Paganelli G, Riva P, Deleide G, Clivio A, Chiolerio F, Scassellati GA, Malcovati M, Siccardi AG. In vivo labelling of biotinylated monoclonal antibodies by radioactive avidin: a strategy to increase tumor radiolocalization.Int J Cancer Suppl 1988; 2: 121–125.
Paganelli G, Pervez S, Siccardi AG, Rowlinson G, Deleide G, Chiolerio F, Malcovati M, Scassellati GA, Epenetos AA. Intraperitoneal radio-localization of tumors pre-targeted by biotinylated monoclonal antibodies.Int J Cancer 1990; 45: 1184–1189.
Paganelli G, Magnani P0, Zito F, Villa E, Stella M, Sudati F, Lopalco L, Rossetti C, Malcovati M, Chiolerio F, Seccamani E, Siccardi AG, Fazio F. Three-step monoclonal antibodies tumor targetting in CEA-positive patients.Cancer Res 1991; 51: 5960–5966.
Paganelli G, Siccardi AG, Malcovati M, Scassellati G, Fazio F. Biotinylated monoclonal antibodies: their potential for diagnosis and therapy of cancer.Curr Opin Ther Pat 1993; 3: 1465–1474.
Paganelli G, Magnani P, Siccardi AG, Fazio F. Clinical application of the avidin-biotin system for tumor targeting. In: Goldenberg DM, ed.Cancer therapy with radiolabeled antibodies. New York: CRC Press; 1995: 239–254.
Goodwin DA. Pharmacokinetics and antibodies.J Nucl Med 1987; 28: 358–1362.
Paganelli G, Magnani P, Zito F, Lucignani G, Sudati F, Truci G, Motti E, Terreni M, Pollo B, Giovanelli M, Canal N, Scotti G, Comi G, Koch P, Maecke HR, Fazio F. Pre-targeted immuno-detection in glioma patients: tumor localization and single photon emission tomography imaging of 99m Tc PnAO-biotin.Eur J Nucl Med 1994; 21: 314–321.
Dosio F, Magnani P, Paganelli G, Samuel A, Chiesa G, Fazio F. Three-step tumor pretargeting in lung cancer immunoscintigraphy.J Nucl Biol Med 1993; 37: 228–232.
Colombo P, Paganelli G, Magnani P, Songini C, Fazio F, Faglia G. Immunoscintigraphy with antibodies in patients with endocrine/neuroendocrine tumors.J Endocrinol Invest 1993; 16: 841–843.
Magnani P, Paganelli G, Siccardi AG, Songini C, Colombo P, Faglia G, Fazio F. Combined use ofJr.In-labeled pentetreotide and three-step immuno-scintigraphy with anti-chromogranin A monoclonal antibody in the diagnosis of pituitary adenomas.Cell Biophys 1994; 24-25: 307–313.
Galen RS, Gambino SR.Beyond normality: the predictive value and efficiency of medical diagnoses. New York: Wiley, 1972.
Sokal RR, Rohlf FJ.Biometry. The principle and practice of statistics in biological research. San Francisco: Freeman, 1981.
Seccamani E, Tattanelli M, Mariani M, Spranzi E, Scassellati GA, Siccardi AG. A simple qualitative determination of human antibodies to murine immunoglobulins (HAMA) in serum samples.Nucl Med Biol 1989; 2: 167–170.
Lamberts SWJ, Bakker WH, Reubi JC, Krenning EP. Somatostatin-receptor imaging in the localization of endocrine tumors.N Engl J Med 1990: 323: 1246–1249.
Kwekkeboom DJ, Krenning EP, Bakker WH, Oei HY, Splinter TAW, Siang Kho G, Lamberts SWJ. Somatostatin analogue scintigraphy in carcinoid tumours.Eur J Nucl Med 1993; 20: 283–292.
Sobol RE, Memoll V, Deftos LJ. Hormone-negative, chromogranin A-positive endocrine tumors.N Engl J Med 1989; 320: 444–447.
Welt S, Mattes MJ, Grando R, Thomson TM, Leonard RW, Zanzonico PB, Bigler RE, Yeh S, Oettgen HE, Old LJ. Monoclonal antibody to an intracellular antigen images human melanoma transplants innu/nu mice.Proc Natl Acad Sci USA 1987; 84: 4200–4204,
Khaw BA, Gold HK, Yasuda T, Leinbach RC, Kanke M, Fallon JT, Barlai-Kovach M, Strauss HW Sheehan F, Haber E. Scintigraphic quantification of myocardial necrosis in patients after intravenous injection of myosin-specific antibody.Circulation 1986; 74: 501–508.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Siccardi, A.G., Paganelli, G., Pontiroli, A.E. et al. In vivo imaging of chromogranin A-positive endocrine tumours by three-step monoclonal antibody targeting. Eur J Nucl Med 23, 1455–1459 (1996). https://doi.org/10.1007/BF01254467
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01254467