Gamma imaging with negatively charge-modified monoclonal antibody: Modification with synthetic polymers

B. A. Khaw, A. Klibanov, S. M. O'Donnell, T. Saito, N. Nossiff, M. A. Slinkin, J. B. Newell, H. W. Strauss, V. P. Torchilin

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Antimyosin Fab has been modified to carry highly negatively charged synthetic polymers containing DTPAs (DTPA-PL) as chelating agents, of starting molecular weights 3.3 and 17 kD. The immunoreactivities of the modified antibodies were unaffected by the modification procedure. The isoelectric points (PI) of unmodified antimyosin (AM) Fab (PI range 7-9, M(r) = 52kD) were changed to PIs predominantly between 4 and 5 (M(r) = 59 kD for DTPA-PL(3.3kD)-AM-Fab and 67kD for DTPA-PL(17kD)-AM-Fab). These AM-Fab preparations were tested for specific target localization and visualization in vivo in an experimental canine model of acute myocardial infarction. The charge-modified 111In-labeled AM-Fab preparations showed enhanced target (necrotic myocardium) visualization within 30 min of intravenous infusion and decreased background activity in normal myocardium (mean %ID/g ± s.e.m., 0.0076 ± 0.0006, n = 164, and 0.0056 ± 0.0004, n = 92, for 111In-DTPA-PL(3.3kD)- and DTPA-PL(17kD)-AM-Fab respectively) relative to conventional 111In-DTPA-AM-Fab (0.0263 ± 0.0037, n = 135) (p < 0.001) or radioiodinated AM-Fab (0.0098 ± 0.0006, n = 256) (p ≤ 0.001). Furthermore, the concentration of negatively charged 111In-labeled antimyosin Fab decreased in non-target organs such as the liver and kidneys. In diagnostic and therapeutic applications, charge-modified macromolecules may improve target localization and reduce non-target organ activity.

Original languageEnglish
Pages (from-to)1742-1751
Number of pages10
JournalJournal of Nuclear Medicine
Volume32
Issue number9
StatePublished - 1991
Externally publishedYes

Fingerprint

Dive into the research topics of 'Gamma imaging with negatively charge-modified monoclonal antibody: Modification with synthetic polymers'. Together they form a unique fingerprint.

Cite this