Biodistribution of a 153 Gd-folate dendrimer, generation = 4, in mice with folate-receptor positive and negative ovarian tumor xenografts

Investigative Radiology
Sheela D KondaErik C Wiener

Abstract

An important characteristic of targeted contrast agents is how they are tolerated in a biologic environment and their localization in the surrounding tissues in addition to target tissue. We evaluate the biodistribution of a gadolinium Gd 153-folate-dendrimer in high affinity folate-receptor (hFR) positive and negative ovarian tumor xenografts. The 153Gd-folate-dendrimer chelate was prepared by exchanging 153Gd with nonradioactive gadolinium for 1 week, followed by extensive filtration. Athymic mice with hFR-positive (n = 3) and negative tumors (n = 3) were injected intravenously and counted using a whole-body counting system with a 80 to 150 keV counting window. The hFR-positive tumors accumulate 3.6% +/- 2.8% injected dose/g, whereas only background counts were found in hFR-negative tumors. The folate-dendrimer's tumor-to-blood ratio of 12.6, in hFR-positive tumors, was approximately 5.7 to 17.0 fold better than those obtained with monoclonal antibodies targeted to the folate receptor. Biodistribution studies confirm previous MRI findings and show that the accumulation of the folate-dendrimer requires the expression of the hFR.

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