Abstract
A major problem that arises when radiolabeled serum proteins are used for tumor imaging is the presence of a large amount of circulating background activity that persists for several days. This delays imaging for at least 2 days following injection and necessitates computer subtraction of simulated background (second radiopharmaceutical injection) which introduces artifacts that are difficult to control. We propose here the injection of specific antibody immediately before imaging as an alternate way of reducing blood background through clearance of the immune complex by the liver.
111In-alkyl human transferrin and IgG were injected IV in BALB/c tumor mice, and followed in 18 h by anti-human transferrin and anti-human IgG antibody IV. Two hours later, the tumor and organ distribution of activity was compared with control mice not receiving antibody. 111In-transferrin blood activity was reduced to 1/48 of control with no decrease in tumor concentration: as a result, the tumor to blood ratio increased from 1.4:1 to 78:1. 111In-IgG blood activity was reduced to 1/17 of control, again with no decrease in tumor. The tumor to blood ratios increased from 0.7:1 to 17:1. The liver picked up most of the blood activity with none of the complex going to spleen, bone marrow, or kidney. Dog experiments showed clearance of blood was 90% complete in less than 15 min following antibody injection. Simultaneous scintillation images showed complete clearance of activity from the heart and great vessels in the chest and neck, and over the abdomen, with a concomitant increase in liver activity but no increase in spleen, kidney, or bone marrow activity. These studies show the feasibility of using specific antibody to lower the blood background just minutes prior to tumor imaging procedures using radiolabeled proteins.
Similar content being viewed by others
References
Ballou B, Lavine G, Hakala TR, Solter D (1979) Tumor location detected with radioactively labeled monoclonal antibody and external scintigraphy. Science 206:844–847
Begent RHJ, Searle F, Stanway G, Jewkes RF, Jones BE, Vernon P, Bagshaw KD (1980) Radioimmunolocalization of tumours by external scintigraphy after administration of 131I antibody to human chorionic gonadotrophin. J R Soc Med 73:624–630
Begent RHJ, Green AJ, Bagshawe KD, Jones BE, Keep PA, Searle F, Jewkes RF, Barratt GM, Ryman BE (1982) Liposomally entrapped second antibody improves tumour imaging with radiolabeled (first) antitumour antibody. Lancet 2:739–742
Benacerraf B, Sebestyen M, Cooper NS (1959) The clearance of antigen antibody complexes from the blood by reticuloendothelial system. J Immunol 82:131–137
Bernhard MI, Foon DA, Clarke GC, Christensen WL, Hoyer L, Key M, Hanna MG, Oldham RK (1982) Monoclonal antibody serotherapy of solid tumors: a guinea pig model. AACR Abstracts 256
Burchiel SW, Khaw BA, Rhodes BA, Smith TW, Haber E (1982) Immunopharmacokinetics of radiolabeled antibodies and their fragments. In: Burchiel SW, Rhodes BA (eds) Tumor imaging, the radioimmunochemical detection of cancer. Masson Publishing USA, New York, pp 125–139
Chatel JF, Saccavini JC, Fumoleau P, Bardy A, Douillard JY, Aubry J, LeMevel B (1982) Photoscanning localization of human tumors using radioiodinated monoclonal antibodies to colorectal carcinoma (abstract). J Nucl Med 23:P8
Chou SN, Aust JB, Moore GE, Peyton WT (1951) Radioactive iodinated human serum albumin as tracer agent for diagnosing and localizing intracranial lesions. Proc Soc Exp Biol Med 77:193–195
Day ED, Planinsek JA, Pressman D (1959) Localization in vivo of radioiodinated anti-fibrin antibodies to Murphy rat lymphosarcoma and other tumors. JNCI 22:413–426
DeLand FH, Kim EE, Simmons G, Goldenberg DM (1980) Imaging approach in radioimmunodetection. Cancer Res 40:3046–3049
DeRiemer LH, Meares CF, Goodwin DA, Diamanti CI (1981) BLEDTA II: Synthesis of a new tumor visualizing derivative of Cobalt (III) bleomycin. J Lab Compd Radiopharm 18:1517–1534
Frank MM, Hamburger MI, Lawley TJ, Kimberly RP, Plotz PH (1979) Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus. N Engl J Med 30:518–523
Goldenberg DM, DeLand FH, Kim EE, Bennett S, Primus FJ, van Nagell JR, Estes N, DeSimone P, Rayburn P (1978) Use of radiolabeled antibodies to carcinomembryonic 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, Bennett S, Primus FJ (1980) Radioimmunodetection of cancer with radioactive antibodies to carcinoembryonic antigen. Cancer Res 40:2984–2992
Goodwin DA, Goode R, Brown L, Imbornone CJ (1971) Indium-111 labeled transferrin for the detection of tumors. Radiology 100:175–179
Goodwin DA, Sundberg MW, Diamanti CI, Meares CF (1975) Indium-111 radiopharmaceuticals in cancer localization. In: 18th Annual Clinical Conference Monograph ‘Radiologic and other biophysical methods in tumor diagnoses’. MD Anderson Hospital and Tumor Institute, Houston Texas. Yearbook Medical Publishers, Chicago, Illinois, pp 57–88
Goodwin DA, Meares CF, Diamanti CI, Bushberg JT (1977) Biological properties of molecules labeled with metal ions using bifunctional chelates. In: Medical radionuclide imaging, IAEA Vienna (1976) 2:61–69
Imai K, Yachi A, Ferrone S (1982) Preparation and characterization of monoclonal antibodies to human melanoma—associated antigens (MAA). In: Burchiel SW, Rhodes BA (eds) Tumor imaging, the radioimmunochemical detection of cancer. Masson Publishing USA, New York, pp 141–150
Jones BE, Green A, Vernon P, Jewkes R, Begent R, Bagshawe KD, Searle F, Keep PA (1982) Technical problems encountered in the use of a dual isotope background subtraction technique in antibody scanning (radioimmunodetection) (abstr). Nucl Med Commun 3:124
Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497
Mach JP, Carrel S, Forni M, Ritschard J, Donath A, Alberto P (1980) Tumor localization of radiolabeled antibodies against carcinoembryonic antigen in patients with carcinoma. N Engl J Med 303:5–10
McCardle RJ, Harper PV, Spar IL, Bayle WF, Andros GN, Jimenez F (1966) Studies with iodine-131 labeled antibody to human fibrinogen for diagnosis and therapy of tumors. J Nucl Med 7:837–847
Meares CF, Sundberg MW, Baldeschwieler JD (1972) Perturbed angular correlation study of a haptenic molecule. Proc Natl Acad Sci USA 69, 12:3718–3722
Miller RA, Maloney DG, McKillop J, Levy R (1981) In vivo effects of murine hybridoma monoclonal antibody in a patient with T cell leukemia. Blood 58:78–86
Miller RA, Maloney DG, Warnke R, Levy R (1982) The treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. New Engl J Med 306:517–522
Monasterio G, Becchini MF, Riccioni N (1964) Radioiodinated (131I and 125I) fibrinogen for the detection of malignant tumors in man. Proc IAEA medical radioisotope scanning 2:159–172
Order SE, Klein JL, Ettinger D (1980) Phase I-II study of radiolabeled antibody integrated in the treatment of primary hepatic malignancies. Int J Radiat Oncol Biol Phys 6:703–710
Pressman D (1980) The development and use of radiolabeled antitumor antibodies. Cancer Res 40:2960–2964
Ritzmann SE, Daniels JC (1982) Immune complexes: Characteristics, clinical correlations and interpretative approaches in the clinical laboratory. Clin Chem 28:1259–1271
Scheinberg DA, Strand M (1982) Leukemic cell targeting and therapy by monoclonal antibody in a mouse model system. Cancer Res 42:44–49
Scheinberg DA, Strand M, Gansow OA (1982) Tumor imaging with radioactive metal chelates conjugated to monoclonal antibodies. Science 215:511–513
Smedley HM, Finan P, Lennox ES, Ritson A, Takei F, Wraight P, Sikora K (1983) Localisation of metastatic carcinoma by a radiolabelled monoclonal antibody. Br J Cancer 47:253–259
Talmage DW, Dixon FJ, Bukantz SC, Dammin GJ (1951) Antigen elimination from the blood as an early manifestation of the immune response. J Immunol 67:243–255
Wahl RL, Parker CW, Philpott GW (1983) Improved radioimaging and tumor localization with monoclonal F(ab′)2. J Nucl Med 24:316–325
Wilbanks AB, Peterson JA, Miller S, Kauffman L, Ortendahl D, Ceriani IL (1981) Localization of mammary tumors in vivo with 131I-labeled Fab fragments of antibodies against mouse mammary epithelial (MME) antigens. Cancer 48:1768–1775
Author information
Authors and Affiliations
Additional information
These studies were supported in part by a Veterans Administration Research Grant, and PHS Grant Number 5 ROI CA 28343 (D Goodwin), and CA 16861, RCDA CA 00462 (C Meares)
Rights and permissions
About this article
Cite this article
Goodwin, D., Meares, C., Diamanti, C. et al. Use of specific antibody for rapid clearance of circulating blood background from radiolabeled tumor imaging proteins. Eur J Nucl Med 9, 209–215 (1984). https://doi.org/10.1007/BF00448541
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00448541