Monitoring tissue responses to vascular-targeted PDT in high resolution

Basic Info of the Study

Research by: Memorial Sloan Kettering Cancer Center is one of the world’s premier cancer centers, collaborating with Weizmann Institute of Science research group.

Modulight products: ML7710 (753 nm)

Laser use: Study effects of vascular-targeted PDT (VTP) in mouse xenograft models

Link to the study:


Dr. Kwanghee Kim

Dr. Avigdor Scherz

 

Vascular-targeted photodynamic therapy

Vascular-targeted photodynamic therapy (VTP) is the latest form of PDT. It was initially developed by Avigdor Scherz (Weizmann Institute of Science), and it’s now owned by Steba Biotech. VTP agent Tookad was clinically approved for low-risk prostate cancer in Europe, Mexico, and Israel after successful multi-center Phase 3 trials. Phase 2 trial has been recently conducted at MSK for intermediate risk prostate cancer by Dr. Jonathan Coleman. VTP is also being investigated for other indications, such as for upper tract urothelial carcinoma in an ongoing Phase 1 trial at MSK. Ongoing preclinical studies explore vascular effects to VTP by optoacoustic and PET imaging as well as improving efficacy by combining VTP with other therapies like immune checkpoint (PD-1/PD-L1) inhibition and androgen deprivation therapy.

 

Dr. Jonathan Coleman has lead clinical VTP trials at MSKCC.

Motivation for the study

Current imaging methods such as MRI, CT, ultrasound or intravital microscopy are either limited by invasiveness or by low special resolution for monitoring vascular responses to VTP therapy. In contrast, raster-scanning optoacoustic mesoscopy (RSOM) imaging has potential to provide non-invasively high-resolution images and was evaluated here for monitoring vascular responses to VTP in mice with subcutaneous CT26 xenografts.

Mechanism of action

WST-11 (Tookad soluble) is administered intravenously and spontaneously forms a noncovalent complex with serum albumin, which circulates in the blood with minimal extravasation to adjacent tissues.

 

Padeliporfin accumulates in endothelial cells, and upon illumination with the 753 nm laser light, it generates an intense local release of cytotoxic reactive oxygen species (ROS).

 

ROS cause damage in the vascular environment, resulting in complete tumor collapse. This therapy preserves adjacent structures and yields excellent functional results.

Study protocol

 

 

Key observations

RSOM imaging showed clear changes in the tumor after VTP. Hemorrhage and occlusion of individual vessels were visible in tumors 1 hour after VTP, while beginning at 48 hours, the whole tumor vascular network collapsed. At day 5 after VTP, RSOM images showed no blood perfusion to the tumor. Tumor death visible in RSOM was confirmed by histological analysis that revealed 90-100% necrosis of tumor tissue and deterioration of blood vessels.

 

RSOM provides quantitative information about treatment effects. Graphs show changes in total vascular area and number of vessel fragments during the study period, as quantified from RSOM images with ImageJ program. See the original related graphs in the referred publication

 

Conclusions:
RSOM imaging proved to be effective method for quantitatively examine sub-millimeter vascular changes in response to vascular-targeted treatment. It enables monitoring both morphological and functional aspects of vessels in noninvasive manner, at much deeper levels than optical microscopy and with very high resolution. The biological mechanisms revealed by RSOM can help in improving the treatment procedures to be even more optimized and effective in the future.

 

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Related Publications

WST11 Vascular Targeted Photodynamic Therapy Effect Monitoring by Multispectral Optoacoustic Tomography (MSOT) in Mice
Volker NeuschmeltingKwanghee KimJaber Malekzadeh-NajafabadiSylvia JebiwottJaya PrakashAvigdor ScherzJonathan A ColemanMoritz F KircherVasilis Ntziachristos
Theranostics, 2018, 8 (3)

 

High-resolution optoacoustic imaging of tissue responses to vascular-targeted therapies

 

 

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