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The biologic behavior of human polyclonal immunoglobulin (IgG) radiolabeled with technetium-99m (99mTc) by a novel method, via a nicotinyl hydrazine derivative, was evaluated in rats. Technetium-99m- and indium-111-IgG were co-administered to normal rats and biodistribution was determined at 2, 6, and 16 hr. The inflammation imaging properties of the two reagents were compared in rats with deep-thigh infection due to Escherichia coli. Blood clearance of both antibody preparations was well described by a bi-exponential function: (99mTc-IgG: t1/2 = 3.82 +/- 0.89 and 57.52 +/- 1.70 hr. 111In-IgG: 3.93 +/- 0.117 and 40.71 +/- 1.26 hr). Biodistributions in the solid organs were similar, however, small but statistically significant differences were detected: 99mTc-IgG greater than 111In-IgG in lung, liver, and spleen; 99mTc-IgG less than 111In-IgG in kidney and skeletal muscle (p less than 0.01). At all three imaging times, target-to-background ratio and percent residual activity for the two compounds were remarkably similar. These studies establish that human polyclonal IgG labeled with 99mTc via a nicotinyl hydrazine modified intermediate is equivalent to 111In-IgG for imaging focal sites of infection in experimental animals.

OKT3 levels and the presence of human antibodies to OKT3 were determined in the plasma of 66 patients receiving OKT3 monoclonal antibody (5 mg i.v. daily) for the treatment of acute renal allograft rejection. Plasma 24-hr trough levels of OKT3 rose over the first three days and then remained in a steady state over the remainder of the 14-day period of OKT3 therapy, with a mean level of 902 +/- 71 ng/ml (mean + SEM). On termination of OKT3 therapy plasma levels of OKT3 dropped to very low levels after 3 days. Host antibodies, usually of low titer, developed in a number of patients, usually 2-3 weeks after the start of OKT3 therapy. 37/43 patients (86%) who received OKT3 alone developed IgG anti-OKT3 antibodies; 9/23 patients (39%) who received Cytoxan in addition to OKT3 developed IgG anti-OKT3 antibodies, a significantly lower (P = 0.0002) incidence. The present regimens permitted maintenance of adequate levels of circulating OKT3 for 2 weeks, a sufficient time to reverse acute renal allograft rejection in most patients.

The immediate side effects of lymphocyte-specific monoclonal antibody treatment of nearly 150 monkeys is documented in this study. Immediate side effects were only seen with antibodies specific for CD3 and CD8. These side effects are most likely related to stimulation of T cells to produce lymphokines (CD3) and/or to the rapid cell clearance (CD3 and CD8). No immediate effects were observed when CD4 or major histocompatibility complex class II-specific antibodies were injected. These antibodies may therefore be considered for the treatment of graft rejection or autoimmune diseases. Of the 43 animals that received a monoclonal antibody (MoAb) at least 2 years and up to 5 years prior to this study, none has shown any late effects of MoAb treatment. Most animals tested had a vigorous immune response to the injected MoAbs, both antiidiotypic as well as anti-isotypic antibodies were formed. This response was reduced by using Fab2 fragments or by additional immunosuppression, but it was still high enough to prevent further effectiveness of the MoAb treatment.