Pharmacokinetics of radiolabeled polyclonal antiferritin in patients with Hodgkin's disease

The objective was to identify pharmacokinetic parameters predictive for tum or response and normal tissue side effects after i.v. administered radiolab eled rabbit antihuman ferritin IgG. Twenty-eight patients with recurrent Ho dgkin's disease received 2 mg of rabbit antihuman ferritin i.v., labeled wi th 4-7 mCi of In-111 followed by two doses of 0.25, one dose of 0.3, or one dose of 0.4 mCi of Y-90-labeled antiferritin per kg of body weight 1 week later. Radioactivity and HPLC measurements of blood and urine samples and l iver and tumor volumes identified on sequential whole-body scans provided t he data for a pharmacokinetic analysis covering the first 6 days after the administration of the radioimmunoconjugate. Side effects and tumor response were recorded. Temporary hematological toxicity was noted in all patients. Sixteen patient s showed a tumor response. The Y-90 blood level at 1 h after administration correlated with the severity of subsequent hematological toxicity. The rap id blood elimination half-life of radioactivity was 4.4 h, Less than 5% of the administered radioactivity was eliminated in the first 24 h urine. The slow blood elimination half-life was 44 and 37 h for In-111 and Y-90, respe ctively. One of 12 retreated patients produced anti-rabbit IgG antibodies. The volume of distribution was larger for Y-90 than for In-111-labeled anti ferritin (160 versus 110% of estimated blood volume). Accidentally extravas ated rabbit IgG was rapidly catabolized in perivascular tissues,vith an eff ective half-life of less than 35 h. Slower catabolism was noted for rabbit IgG in blood (t(1/2) = 40 h), liver (t(1/2) = 62 h) or tumor (t(1/2) = 40-8 0 h). Twelve of 13 patients with an effective tumor half-life > 57 h showed a tumor response. i.v. administered polyclonal rabbit antihuman ferritin, labeled with In-111 or Y-90 is stable in vivo and targets Hodgkin's disease. Intravascular Y-9 0 causes a vascular leak and a larger volume of distribution for antiferrit in. Elevated Y-90 blood levels at 1 h and a tumor half-life of >57 h predic t for hematological toxicity and tumor response, respectively.