131I-labeled antibodies to human fibrinogen.Diagnostic studies and therapeutic trials

Abstract

Homologous 131I fibrinogen and its purified antibody will concentrate in a major portion of the neoplasms of the dogs and humans into which they are injected, according to new data. This report gives the scintillation scanning results obtained after iv administration of 131I‐labeled and purified antihuman fibrinogen to 172 consecutive patients with various types of neoplasms. In 75% (129/172) of the cases the tumor, in various sites, was unequivocally located. These included mammary carcinomas (12/17), malignant melanoma (16/26), bronchogenic carcinoma (27/34), osteogenic sarcomas (9/9), hypernephromas (6/6), and primary tumors of the brain (10/18). The 131I deposition in tumor relative to normal tissue and blood was so great that in 12 terminal patients therapeutic trials were initiated using 100 to 160 me of the labeled antibody preparation. In some of these attempts, there was substantial remission of clinical symptoms. The usefulness of this technique for specific radiation therapy of tumors will be greatly improved when methods are developed for increasing 131I concentration in the peoplasm. Several approaches, including fever, endotoxin, pretreatment with fibrinolytic agents and post‐treatment with antifibrinolytic agents, are under intensive investigation in experiments and offer great promise.

Studies on the localization of radiolabeled antibodies to a mouse myeloma protein

“…T h e vast complexity of antigens normally associated with the cell surface, or else with particulate fractions prepared by centrifugation of tumor homogenates, makes it very difficult to prepare tumor-localizing antibodies by immunization with such preparations, followed by absorption of the antiserum with equivalent materials derived from the corresponding normal cells.3~' However, a normal body constituent that localizes at the site of tumor metastases, namely fibrinogen, has been used successfully for detection of metastases by photoscans of patients injected with trace-radioiodinated antibody to it, and therapy has been attempted. 14 T h e ideal situation for preparation of tumor-localizing antibodies would require the tumor to be freely permeable to systemically circulating antibodies? and to possess antigens that are present in relative abundance on the surface of all tumor cells and are insoluble, purifiable, and sufficiently distinct from normal body constituents to exclude cross-reactions with antibodies prepared against the purified antigen(s).…”

“…From the slopes of these lines, the rate of excretion of antibody was estimated at 42% per day, while that of normal rabbit yG was only 24% per day. These values fit in with the above explanation for the low localization ratios seen on day 14 ( Table 2). …”

Fibrin as a component of the tumor stroma: origins and biological significance

“…This work was subsequently confirmed in studies seeking to employ radiolabeled fibrinogen as an agent for human brain tumor localization by photoscreening procedures (20,21). The first direct demonstration of fibrin in the solid tumor stroma was that of Hiramoto et al (22,23) who employed the immunofluorescence technique on frozen sections of rat and human neoplasms.…”

Improved long-term survival for unresectable hepatocellular carcinoma (HCC) with a combination of surgery and intrahepatic arterial infusion of 131 I-anti-HCC mAb. Phase I/II clinical trials

“…RIT, using radiolabelled antibodies as tumorcidal agents, is one of the more attractive approaches to cancer treatment and has been investigated for more than three decades (Spar et al 1967). Much has been done and much remains to be done (Goldenberg et al 1994).…”