The effect of unlabelled monoclonal antibody (mAb) on the biodistribution of 131I-anti-idiotype mAb in murine B cell lymphoma

ArticleinRadiotherapy and Oncology 24(3):169-76 · August 1992with2 Reads
DOI: 10.1016/0167-8140(92)90376-6 · Source: PubMed
The 38C13 murine B cell lymphoma model was used to study the effect of the preinjection of unlabelled anti-idiotype monoclonal antibody (mAb) on the subsequent biodistribution of 131I-anti-idiotype mAb. Mice with established tumors received 0-500 micrograms of unlabelled anti-idiotype mAb 24 h prior to the administration of 131I-anti-idiotype (specific), or both 125I-anti-idiotype and 131I-isotype-matched irrelevant control (nonspecific) mAb. Mice were counted daily in a gamma counter and sacrificed at 2-144 h following injection. Mice were dissected and the weight and activity of the animals and organs were measured. Mice were bled periodically and circulating idiotype levels were measured using an ELISA assay. Five hundred micrograms of unlabelled anti-idiotype mAb increased the retention time of the specific but not the nonspecific mAb in all organs and tumor. Following pretreatment with unlabelled mAb, the cumulative tumor/whole body and tumor/normal organ ratios became similar to those of the nonspecific mAb, with concentration ratios (specific/nonspecific mAb) of approximately 1, which persisted until 96 h post injection when circulating idiotype reappears in antigen excess. In the absence of unlabelled mAb there was less retention in tumor and normal tissue. This is presumed to be due in part to decreased levels of circulating 131I-mAb secondary to rapid plasma clearance of antigen-antibody complexes and tumor cell mediated dehalogenation, which results when the specific mAb specifically binds the targeted antigen. Thus, the addition of unlabelled mAb increased the retention by decreasing the specific behavior of the anti-idiotypic antibody.
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  • [Show abstract] [Hide abstract] ABSTRACT: Objectives: To study the effect of co-injecting unlabelled hypericin (Hyp) on biodistribution, necrosis uptake and tumour retention of iodine-123 or iodine-131 labelled hypericin ((123/131)I-Hyp), a necrosis avid agent for an anticancer radiotherapy. Methods: (123/131)I-Hyp was prepared with Iodogen as oxidant and formulated in 0.6 μg/kg no-carrier-added (NCA) or 0.25 mg/kg unlabelled Hyp carrier-added (CA) forms using dimethyl sulfoxide/polyethylene glycol-400/propylene glycol/water (25/25/25/25% v/v/v/v), as solvent mixture. Comparisons on biodistribution and necrosis uptake of NCA and CA(123)I-Hyp were conducted on rats (n=24) of reperfused liver infarction (RPLI) in 48h p.i. Tumour retention of CA(131)I-Hyp was assessed in severe combined immunodeficiency (SCID) mice with fibrosarcoma (RIF-1) tumours (n=25) over 40 days. To cause intratumour necrosis, mice were pre-treated with a vascular disrupting agent CA4P at 10mg/kg. Tissue-gamma counting (TGC), autoradiography and histology were performed. Results: TGC revealed no significant difference in organ biodistribution between RPLI-rats injected with NCA and CA(123)I-Hyp, except in intestines, liver, lungs and stomach (P<0.05). Both preparations showed hepatobiliary excretion since intestines and faeces retained the most radioactivity. NCA and CA(123)I-Hyp exhibited high avidity and selectivity for hepatic infarction. From the day after injection onward, CA(123)I-Hyp showed greater target accumulation (7-11%ID/g) than (123)I-Hyp alone (~4%ID/g; P<0.05). In RIF-1-SCID mice receiving CA(131)I-Hyp, prolonged high retention in tumour necrosis was detected over 40 days p. i. TGC findings were confirmed by histological and autoradiographic analysis. Conclusions: The study demonstrated the co-injection of unlabelled Hyp affected necrosis uptake but almost no biodistribution of radioiodinated Hyp. Long-term high retention into tumour necrosis characterizes the carrier-added (131)I-Hyp.
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