Detection of cell death in tumors by using MR imaging and a gadolinium-based targeted contrast agent

Radiology
Anant S KrishnanKevin Brindle

Abstract

To prospectively determine in an animal model whether an ionic gadolinium (Gd(3+)) chelate conjugate of the C2A domain of synaptotagmin I can be used with magnetic resonance (MR) imaging to detect tumor cell death noninvasively in vivo. Animal experiments were approved by a local ethics review committee. Gd(3+) chelates and fluorescent probes were attached to the lysine epsilon-amino groups of a glutathione-S-transferase-C2A fusion protein. Binding to phosphatidylserine (PS) was characterized by using surface plasmon resonance, and binding to dying cells in vitro was characterized by using flow cytometry and MR imaging. Binding to dying tumor cells in vivo was detected with T1 mapping and T1-weighted MR imaging and compared in drug-treated animals (n = 10); in animals injected with a site-directed mutant, which was inactive in PS binding (PS inactive) and which showed lesser binding to dying cells (n = 6); and in untreated animals injected with PS-active (n = 6) and PS-inactive (n = 6) contrast agents. Among groups, differences that were significant were analyzed by using analysis of variance and Dunnett post hoc analysis. The contrast agent had a relatively high affinity for PS (dissociation constant = 333 nmol/L +/- 85 [mean ...Continue Reading

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