Abstract
A new method for intraperitoneal tumour targetting in ovarian cancer using biotinylated monoclonal antibodies (MoAb) and radioactive streptavidin is described. Fifteen patients with histologically documented ovarian carcinoma were injected intraperitoneally with 2 mg of biotinylated MoAb MOv18, followed 3–5 days later by 100–150 μg of indium-111 streptavidin, at the specific activity of 280–370 MBq/mg in 500 ml of normal saline. No toxicity was observed. Tumours were imaged from 2 to 48 h after radioactivity injection by recording both planar and single photon emission tomography (SPET) data. All patients underwent surgery 1–8 days later (mean 3 days) after scanning. The resected tumour and normal tissue radioactivity were measured. On the day of surgery, the tumour to normal tissue ratio was 9:1 (range 3:1–30:1) and 45:1 (range 12:1–120:1) for intra- and extraperitoneal samples, respectively. The mean tumor to blood ratio was 14:1 (range 4:1–30:1). The injected dose (i.d.) per gram of tumour was 0.112 (range 0.01–0.3) for recurrences and 0.05 for primary tumour (range 0.005–0.2). Over 24–48 h 14% i.d. (range 8–18% i.d.) was found in the urine, 14% i.d. (range 629% i.d.) in the blood and 63% i.d. (range 56–70% i.d.) was still in the peritoneal cavity. These preliminary clinical data suggest that this two-step strategy may be superior to the conventional approach (radiolabelled antibodies) for intraperitoneal radioimmunolocalization and radioimmunotherapy of ovarian cancer.
Similar content being viewed by others
References
Buist MR, Hollander W den, Roos JC, Vermoken JB, Greuter HN, Molthoff CFM, Nijam HW, Baak JPA, Burger CW, Kenemans P (1991) Tissue distribution and kinetics of chimeric monoclonal antibody MOvl8 in patients with ovarian cancer. Eighth International Hammersmith Meeting, Porto Carras, Halkidiki, Greece, 8–13 May 1991
Buraggi GL, Callegaro L, Mariani G, Turrin A, Cascinelli N, Attili A, Bombardieri E, Terno G, Plassio G (1985) Imaging with 131I-labeled monoclonal antibodies to a high-molecular-weight melanoma-associated antigen in patients with melanoma: efficacy of whole immunoglobulin and its F(ab′)2 fragments. Cancer Res 45:3378–3387
Chatal JF, Fumoleau P, Saccavini JC, Thedrez P, Curtet C, BiancoArco A, Chetanneau A, Peltier P, Kremer M, Guillard Y (1987) Immunoscintigraphy of recurrences of gynecologic carcinomas. J Nucl Med 28:1807–1819
Colcher D, Esteban J, Carasquillo JA, Sugarbaker P, Reynolds JC, Bryant G, Larson SM, Schlom J (1987) Complementation of intracavitary and intravenous administration of a monoclonal antibody (B72.3) in patients with carcinoma. Cancer Res 47:4218–4224
Colnaghi MI, Buraggi GL, Canevari S, Re F Di, Leoni 0F, Mangioni C, Menard S, Orlandi R (1989) Evaluation of the suitability of a monoclonal antibody raised against human ovarian carcinoma for therapeutic approaches. Nucl Med Biol 16:633–636
Crippa F, Buraggi GL, Re E Di, Gasparini M, Seregni E, Canevari S, Gadina M, Presti A, Marini A, Seccamani E (1991) Radioimmunoscintigraphy of ovarian cancer with the MOv18 monoclonal antibody. Eur J Cancer 27:724–729
Cutler SJ, Myers MH, Green SB (1975) Trends in survival rates of patients with cancer. N Engl J Med 293:122–124
Doussal JM Le, Martin M, Gautherot E, Delage M, Barbet J (1989) In vitro and in vitro targeting of radiolabeled monovalent and divalent haptens with dual specificity monoclonal antibody conjugates: enhanced divalent hapten affinity for cellbound antibody conjugate. J Nucl Med 30:1358–1366
Einhorn N, Nilsson B, Sjovall K (1985) Factors influencing survival in carcinoma of the ovary. Cancer 55II:2019–2025
Epenetos AA, Britton KE, Mather S, Shepherd J, Granowska M, Taylor-Papadimitriou J, Nimmon CC, Durbin M, Hawkins LR, Malpas JS, Bodmer WS (1982) Targeting of iodine-123-labelled tumor associated monoclonal antibodies to ovarian, breast, and gastrointestinal tumors. Lancet II:999–1004
Epenetos AA, Munro AJ, Stewart JSW, Rampling R, Lambert HE, McKenzie CG, Souter P, Rahemtulla A, Hooker G, Sivolapenko GB, Snook D, Courtney-Luck N, Dhokia B, Krauk T, Bodmer WE (1987) Antibody-guided irradiation of advanced ovarian cancer with intraperitoneally administered radiolabeled monoclonal antibodies. J Clin Oncol 5:1890–1899
Goodwin DA, Meares CF, McCall MJ, McTigue M, Chaovapong W (1988) Pre-targeted immunoscintigraphy of murine tumors with 111-indium-labeled bifunctional haptens. J Nucl Med 29:226–234
Hird V, Stewart JSW, Snook D, Dhokia B, Coulter C, Lambert HE, Mason WP, Soutter WP, Epenetos AA (1990) Intraperitoneally administered 90Y-labelled monoclonal antibodies as a third line of treatment in ovarian cancer. A phase 1–2 trial: problems encountered and possible solutions. Br J Cancer 62 [Suppl X]:48–51
Hnatowich DJ, Layne WW, Childs RL, Lanteigne D, Davis MA, Griffin TW, Doherty PW (1983) Radioactive labelling of antibody: a simple and efficient method. Science 220:613–615
Hnatowich DJ, Virzi F, Rusckowski M (1987) Investigations of avidin and biotin for imaging applications. J Nucl Med 28:1294–1302
Jain RK (1988) Determinants of tumor blood flow: a review. Cancer Res 48:2641–2658
Larson SM, Carasquillo JA, Colcher DC, Yokoyama K, Reynolds JC, Bacharach SA, Raubitchek A, Pace L, Finn RD, Rotman M, Stabin M, Neumann RD, Sugarbaker P, Schlom J (1991) Estimates of radiation absorbed dose for intraperitoneally administered iodine 131 radiolabeled B72.3 monoclonal antibody in patients with peritoneal carcinomatoses. J Nucl Med 32:1661–1667
Lastoria S, Castelli L, Caracó C, Vergara E, Panza N, Salvatore M (1991) Radioimmunoscintigraphy with I-131-MOv18 F(ab′)2 in patients with ovarian tumors: phase 1 study. XIX Meeting of the International Society of Oncodevelopmental Biology and Medicine, Siena, Italy, 13–17 October 1991
Mariani M, Bonelli F, Tarditi L, Calogero R, Camagna M, Spranzi E, Seccamani E, Deleide G, Scassellati GA (1989) Purification of monoclonal antibodies for in vivo use: a two step HPLC shows equivalent performance to immunoaffnity chromatography. Biochromatography 4:149–155
Meares CF, Moi MK, Diril H, Kukis DL, McCall MJ, Deshpande SV, DeNardo SJ, Snook D, Epenetos AA (1990) Macrocyclic chelates of radiometals for diagnosis and therapy. Br J Cancer 62 [Suppl 10]:21–26
Miotti S, Canevari S, Menard S, Mezzanzanica D, Porro G, Pupa SM, Regazzoni M, Tagliabue E, Colnaghi MI (1987) Characterization of human ovarian carcinoma-associated antigens defined by novel monoclonal antibodies with tumor-restricted specificity. Int J Cancer 39:297–303
Neijt JP, Ten Bokkel Huinink WW, Burg MEL Van der, Oosterom AT van, Vriesendorp R, Koouman CD, Lindert ACM van, Hammlynk JVTH, Lent M van, Honwelingen JC van, Pinedo HM (1984) Randomised trial comparing two combination chemotherapy regimes (Hexa-CAF vs CHAP-5) in advanced ovarian carcinoma. Lancet II:594–600
Paganelli G, Riva P, Sarti G, Tison V, Cacciaguerra G, Fiorentini G, Moscatelli G, Benini S, Agostini M (1986) Intraperitoneal versus intravenous injection radiolabelled monoclonal antibodies in patients with colorectal carcinoma. Br J Cancer 54:542
Paganelli G, Riva P, Moscatelli G, Stacchiotti A, Agostini ME, Landi G, Tison V, Pancea P, Siccardi AG (1986) Improved immunoscintigraphy by subcutaneous injection of 99mTc- or 111In-labelled F(ab′)2 fragments of an anti-melanoma monoclonal antibody. Nucl Med Biol 13:423–428
Paganelli G, Riva P, Deleide G, Clivio A, Chiolerio F, Scassellati GA, Malcovati M, Siccardi G (1988) In vivo labelling of biotinylated monoclonal antibodies by radioactive avidin: a strategy to increase tumor radiolocalization. Int J Cancer [Suppl 2]: 121–125
Paganelli G, Pervez S, Siccardi AG, Rowlinson G, Deleide G, Chiolerio F, Malcovati M, Scassellati GA, Epenetos AA (1990) Intraperitoneal radio-localization of tumors pre-targeted by biotinylated monoclonal antibodies. Int J Cancer 45:1184–1189
Paganelli G, Malcovati M, Fazio F (1991) Monoclonal antibody pretargetting techniques for tumour localization: the avidinbiotin system. Nucl Med Commun 12:211–234
Pervez S, Paganelli G, Epenetos AA, Moor WJ, Evans DJ, Krausz T (1988) Localization of biotinylated monoclonal antibody in nude mice bearing subcutaneous and intraperitoneal human tumor xenografts. Int J Cancer [Suppl 3]:30–33
Ruser G, Ritter W, Maecke H (1990) Synthesis and evaluation of two new bifunctional carboxymethylated tetraazamacrocyclic chelating agents for protein labeling with indium-111. Bioconjugate Chem 1:345–349
Seccamani E, Tattanelli M, Mariani M, Spranzi E, Scassellati GA, Siccardi AG (1989) A simple qualitative determination of human antibodies to murine immunoglobulins (HAMA) in serum samples. Nucle Med Bio1 2:167–170
Siccardi AG, Buraggi GL, Callegaro L, Centi Colella A, Filippi PG De, Galli G, Mariani G, Masi R, Palumbo R, Riva P, Salvatore M, Scassellati GA, Scheidhaurer K, Turco GL, Zaniol P, Benini S, Deleide G, Gasparini M, Lastoria S, Mansi L, Paganelli G, Salvischiani E, Seregni E, Viale G, Natali PG (1989) Immunoscintigraphy of adenocarcinomas by means of radiolabeled F(ab′)2 fragments of an anticarcinoembryonic antigen monoclonal antibody: a multicenter study. Cancer Res 49:3095–3103
Silverberg E, Luberg J (1987) Cancer statistics 1987. CA 37:2–19
Snyder WS, Ford MR, Warner GG, et al. (1975) “S’ absorbed dose per unit cumulated activity for selected radionuclides and organs. (MIRD pamphlet no. 11) Society of Nuclear Medicine, New York
Stewart JSW, Hird V, Snook D, Sullivan M, Hooker G, Courtenay-Luck N, Stivolapenko G, Griffths M, Myers MJ, Lambert HE, Munro J, Epenetos AA (1989) Intraperitoneal adioimmunotherapy for ovarian cancer: pharmacokinetics, toxicity, and efficacy of I-131 labeled monoclonal antibodies. Int J Radiat Oncol Biol Phys 16:405–413
Young RC, Knapp RC, Perez CA (1982) Cancer of the ovary. In: Vita VT de Jr, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology, Lippincott, Philadelphia, pp 884–913
Ward BG, Mather SJ, Hawkins LR, Crowther ME, Shepherd JH, Granowska M, Britton KE, Slevin ML (1987) Localization of radioiodine conjugated to the monoclonal antibody HMFG2 in human ovarian carcinoma: assessment of intravenous and intraperitoneal routes of administration. Cancer Res 47:4719–4723
Watson EE, Stabin MG, David J, Eckerman K (1989) A model of the peritoneal cavity for use in internal dosimetry. J Nucl Med 30:2002–2011
Author information
Authors and Affiliations
Additional information
Offprint requests to: G. Paganelli
Rights and permissions
About this article
Cite this article
Paganelli, G., Belloni, C., Magnani, P. et al. Two-step tumour targetting in ovarian cancer patients using biotinylated monoclonal antibodies and radioactive streptavidin. Eur J Nucl Med 19, 322–329 (1992). https://doi.org/10.1007/BF00177053
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00177053