Disulfide cross-linked Fab-aggregates: Preparation and biodistribution

S. Dalkara, A. Petrov, V. S. Trubetskoy, B. A. Khaw, V. P. Torchilin

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


The high-molecular-weight soluble aggregates of Fab fragments of murine antibodies against cardiac myosin were prepared as a potential long-circulating and low immunogenic pharmaceutical carriers by conjugation of thiolated Fab and Fab modified with succinimidyl 3-(2-pyridyldithio)propionate. The clearance time and biodistribution of 111In-radiolabeled aggregates were studied in normal and nude-mice bearing human breast tumor implant and in rabbits with experimental myocardial infarction. The aggregates had a prolonged circulation time (half clearance time ca. 3-5 h) and ability to concentrate in the tumor and in the necrotic area of infarcted myocardium. Similar tumor-to-normal and infarct-to-normal accumulation ratios (ca. 3 h in both cases) suggest that combination of long circulation with impaired filtration in necrotic tissues is responsible for this accumulation rather than a specific interaction. The aggregates prepared may serve as long-circulating drug carriers able to deliver pharmaceuticals into areas with affected and leaky vasculature.

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalJournal of Drug Targeting
Issue number1
StatePublished - 1998
Externally publishedYes


  • Aggregates of monoclonal antibody fragment
  • Antimyosin antibody
  • Biodistribution
  • Long-circulating pharmaceutical carrier


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