The Story of Tookad: From Bench to Bedside

Authored by: Avigdor Scherz , Yoram Salomon

Handbook Ofphotomedicine

Print publication date:  October  2013
Online publication date:  October  2013

Print ISBN: 9781439884690
eBook ISBN: 9781439884706
Adobe ISBN:

10.1201/b15582-43

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Abstract

Tookad (TOOKAD®, WST09) and Tookad Soluble (TS), two derivatives of the photosynthetic pigment bacteriochlorophyll (Bchl-D), represent a new photosensitizer generation and a new paradigm in photodynamic therapy (PDT) of cancer. The novel approach known as vascular targeted PDT with Tookad or TS vascular targeted photodynamic therapy (TS VTP) has attained advanced clinical trials in the treatment of localized prostate cancer (Arumainayagam et al. 2011; Azzouzi et al. 2011; Moore et al. 2009, 2011). In essence, following intravenous (IV) administration, the new Bchlds spontaneously form complexes with plasma proteins and stay in the circulation until cleared from the body with minimal or no extravasation. Nearinfra-red (NIR) illumination of these circulating Bchlds generates reactive oxygen species (ROS) in the form of superoxide, hydrogen peroxide, and hydroxyl radicals. Importantly, these differ from singlet oxygen generated solely by most currently used PDT photosensitizers. In addition to acute ROS generation, secondary reactive nitrogen species (RNS) are formed. The cogeneration of these radicals in the vascular lumen leads to a plantlike hypersensitive response also seen in animals during ischemia reperfusion injury, resulting in the instantaneous tumor vascular occlusion with permanent dysfunction followed by rapid necrosis/apoptosis of the tumor tissue. Tumor ablation through radicalbased processes known to trigger localized organ collapse in plants and animals in response to various pathological threats suggests a novel paradigm for cancer therapy. The progression of this treatment approach from the bench to the bedside has involved the crossing of traditional scientific disciplines and extensive interdisciplinary collaboration between research groups in academia, medical practice, and the pharmaceutical industry. This chapter describes milestones on the road to reaching that goal.

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