Novel Prodrugs for Targeting Diagnostic and Therapeutic Radionuclides to Solid Tumors

Abstract

Most cancer therapeutics (chemo, radiation, antibody-based, anti-angiogenic)are at best partially and/or temporarily effective. In general, the causes for failure can besummarized as: (i) poor diffusion and/or nonuniform distribution of drug/prodrugmolecules in solid tumors; (ii) high drug concentration and retention in normal tissues(leading to side effects); (iii) requirement for plasma-membrane permeability and/orinternalization of drug/prodrug molecules; (iv) low uptake of drug by tumor; (v) lack ofretention of drug within tumor (most have gradient-driven reversible binding); and (vi)multidrug resistance. We are developing an innovative technology that aims to surmountthese problems by actively concentrating and permanently entrapping radioimaging andradiotherapeutic prodrugs specifically within solid tumors. The approach will enablenoninvasive sensing (imaging) and effective therapy of solid tumors, allowing tumordetection, diagnosis, and treatment to be closely coupled (personalized medicine).

Keywords

• Prodrug
• solid tumors
• radioiodine
• radioimaging
• radiotherapy