PARENT SESSION
1:30 PM to 3:30 PM
Tuesday, April 23, 2002
Poster Session 22 Radioimmune Therapies
Room: Nevada Exhibition Center

(P27-277) Synthesis and Biologic Evaluation of a Radioiodinated Quinazolinone Derivative for Enzyme-Mediated Insolubilization Therapy.

Kassis, Amin^*,1, Ho, Nan-hui¹, Harapanhalli, Ravi¹, Adelstein, James¹, ¹ Department of Radiology, Boston, MA

ABSTRACT-
We have developed a new strategy that aims to concentrate therapeutic radionuclides within solid tumors. This approach, which we have named EMIT (Enzyme-Mediated Insolubilization Therapy), is a method for enzyme-dependent, site-specific, in-vivo precipitation of a radioactive molecule (from a water-soluble precursor) within the extracellular space of solid tumors. The prodrug, ammonium 2-(2'-phosphoryloxyphenyl)-6-iodo-4-(3H)-quinazolinone, labeled with iodine-125 (¹²⁵IPD) and its authentic compound labeled with iodine-127 (IPD) have been synthesized, purified, and characterized. The alkaline-phosphatase (ALP)-mediated conversion of these water-soluble nonfluorescent prodrugs to the water-insoluble fluorescent species, iodine-125-labeled 2-(2'-hydroxyphenyl)-6-iodo-4-(3H)-quinazolinone (¹²⁵ID) and its ¹²⁷I-labeled derivative (ID) has been demonstrated in vitro. Biodistribution studies in mice indicate that both ¹²⁵IPD and ¹²⁵ID are minimally retained by most tissues and organs. In addition, following its intravenous injection in mice, ¹²⁵IPD is localized in ALP-rich regions and converted to ¹²⁵ID, which remains indefinitely within the tissues where it is produced. We believe that EMIT is a strategy that will lead to the active and specific concentration and entrapment of therapeutic radionuclides within solid tumors, the consequent protracted irradiation of tumor cells within the range of the emitted particles, and the effective therapy of solid tumors.

KEYWORDS: iodine-131, cancer therapy, antibody, prodrug