Monitoring tissue responses to vascular-targeted PDT (VTP) 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

The following pictures are extraction of the illumination study from the original research.

 


Graphs from the original publication. Reproduced with permission from the contact author of the publication.

 

 

Conclusions:
The tumors demonstrated visible changes after VTP, with slight redness and swelling at 24 h and eschar, oedema and necrotic tissue at 48 h, which began to shrink at 5 days after VTP. RSOM images showed hemorrhage and occlusion of individual vessel at 1h after VTP, while beginning at 48 h, the whole tumor vascular network collapsed and defined vessel structures resolved. Based on the results, RSOM proved to be effective method for monitoring sub-millimeter changes in fine vascular structures in response to VTP.

 

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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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