Theranostic Pretargeting Drug Delivery and Imaging Platforms in Cancer Precision Medicine

Abstract

Theranostics are nano-size or molecular-level agents serving for both diagnosis and therapy. Structurally, they are drug delivery systems integrated with molecular or targeted imaging agents. Theranostics are becoming popular because they are targeted therapeutics and can be used with no or minimal changes for diagnostic imaging to aid in precision medicine. Thus, there is a close relation between theranostics and image-guided therapy (IGT), and theranostics are actually a subclass of IGT in which both therapeutic and imaging functionalities are attributed to a single platform. An important theranostics strategy is biological pretargeting. In pretargeted IGT, first, the target is identified by a target-specific natural or synthetic bioligand followed by a nano-scale or molecular drug delivery component, which form therapeutic clusters by in situ conjugation reactions. If pretargeted drug delivery platforms are labeled with multimodal imaging probes, they can be used as theranostics for both diagnostic imaging and therapy. Optical and nuclear imaging techniques have mostly been used in proof-of-concept studies with pretargeted theranostics. The concept of pretargeting in theranostics is comparatively novel and generally requires a confirmed overexpression of surface receptors on targeted cells/tissue. In addition, the receptors should have natural or synthetic bioligands to be used as pretargeting components. Therefore, applications of pretargeting theranostics are still limited to several cancer types, which overexpress cell-surface markers on the target cancer cells. In this review, recent discoveries of pretargeting theranostics in breast, ovarian, prostate, and colorectal cancers are discussed to highlight main strengths and potential limitations the strategy.

Biotin-streptavidin-guided two-step pretargeting approach using PLGA for molecular ultrasound imaging and chemotherapy for ovarian cancer

“…The two-step biotin-avidin pre-targeting technology has the characteristics of strong binding in vivo and multi-level amplification and has been applied in other imaging fields ( Qiu et al, 2015 ). The T/NT value using a pre-targeting technique is significantly higher than that of direct targeting methods ( Hapuarachchige & Artemov, 2020 ; Hapuarachchige et al, 2020 ; Imberti et al, 2020 ). However, this method is rarely used in ultrasound molecular targeting research.…”

Nanomaterials-Mediated Immunomodulation for Cancer Therapeutics

“…The recent trend is to apply nanotechnology to design alternative treatment approaches which can induce therapeutic effects at the target site while causing minimum collateral damage and adverse effects ( Li, T. et al, 2020 ; Tan et al, 2020 ). Unlike conventional cancer therapies, this approach provides a more precise and personalized therapeutic effect that causes minimum side-effects and allows simultaneous imaging of the target site (monitoring) ( Hapuarachchige and Artemov, 2020 ; Xu, C. M. et al, 2020 ). As a result, the technique of induced immunomodulation has gained popularity as a tool for cancer therapy ( Comparetti et al, 2018 ; Li, J. et al, 2019 ; Xu, B. et al, 2020 ).…”

Theranostic Advances in Breast Cancer in Nuclear Medicine

“…In order to evaluate effectiveness of the therapeutic procedure, the first diagnostic imaging with radioiodine was performed in 1950 at the University of California, Los Angeles (UCLA) [ 33 ]. Pre-targeting verification includes sensitivity, specificity and quantification imaging studies to prove the therapeutic feasibility of a specific radiotracer [ 34 ].…”

“…Nowadays, this exclusive integration of diagnosis and therapy are common. The most recent progress in this precedent is the administration of those radiotheranostic agents which target somatostatin receptors (SSTRs) in neuroendocrine tumours (NETs), human epidermal growth factor receptor 2 (HER2) antigens in BC and the prostate specific membrane antigen (PSMA) in prostate cancer (PC) [ 30 , 34 , 35 ]. The two prevalent ligands for NET are DOTA-Phe1-Tyr3-octreotide (DOTA-TOC) and DOTA-DPhe1,Tyr3-octreotate (DOTA-TATE) widely used worldwide [ 36 , 37 , 38 , 39 ].…”