PET Imaging Utilizing ⁸⁹Zr-labeled Human Antibody Variant and Theranostic Technologies Provided by a Novel DDS Carrier

Abstract

“Theranostics” represents a ground-breaking concept of medical modality featuring a hybrid of therapeutic and diagnostic systems. We have recently fabricated a 27 kDa single chain variable fragment （scFv）, which is essentially a humanized and shortened variant of IgG to establish clinically-applicable PET imaging and theranostics in cancer medicine. A target molecule is mesothelin, a 40 kDa-tumor differentiation-related cell surface glycoprotein antigen, that is frequently expressed by malignant tumors. The theranostics system which comprises of a novel ⁸⁹Zr-labeled drug delivery system （DDS）, derived from novel biodegradable polymeric micelle, “Lactosome”, conjugated with specific scFv, aims to successfully deliver therapeutically effective molecules, such as, apoptosis-inducing small interfering RNA （siRNA）, into targeted cells and to offer simultaneous visualization of targets via PET imaging. In particular, the combination of photodynamic therapy （PDT） with 5-aminolevulinic acid （ALA） and photo-controlled intracellular siRNA delivery system further offers a promising theranostic-based system, ideally via its targeted apoptosis-inducing feature.