Optimizing photosensitizer administration for cancer therapy

Customer case

University of Rochester belongs among nation’s top research universities. Research at the Baran lab focuses on anti-microbial PDT and optical image processing. Aim is to develop methods for utilizing quantitative information from CT, MR and PET imaging for PDT treatment planning as well as in the search of new biomarkers and therapeutic targets.

Modulight products: ML7710 (630 & 665 nm)

Link to the study:


Timothy M. Baran
(Ph.D., PI)

Laser use: Ongoing clinical Phase 1 safety & feasibility study for methylene blue mediated PDT to sterilize infected deep tissue abscesses (collection of pus). In this dose-escalation trial, one study goal is to determine the optimal illumination time. The advantages of this treatment include reduced surgical intervention, decreased spread of infection, and shortened course of antibiotic therapy. Also preclinical studies ongoing for oncological indications.

 

 

Motivation

While Photofrin PDT is approved oncological therapy for multiple indications, its wider use is hindered by prolonged skin photosensitivity lasting several weeks. The aim of this study is to investigate intratumoral Photofrin administration as a way to decrease skin photosensitivity compared to the standard IV injection protocol. Tumor necrosis after PDT was assessed with immunohistochemical staining and Photofrin distributions by fluorescence microscopy.

 

 

Illumination

Type: Interstitial

Laser model: ML7710

Wavelength: 630 nm

Power: 400 mW/cm2

Fluence: 100 J/cm2

Drug light interval:
0.25 h (for intratumoral)
or 48 h (for IV)

Intravenous drug administration 

Intratumoral drug administration

 

Results

 
Route of administration Photofrin dose (mg/kg) Average tumor necrosis (mm) Average skin photosensitivity
Intratumoral (n=14) 0.5 6.8 ± 1.3 Little to no
1 7.8 ± 1.4
2 5.8 ± 1.6
Intravenous (n=9) 2 5.5 ± 2.1 Evident reddening & swelling

 

Anti-tumor efficacy was similar between intratumoral and IV administration, however smaller doses of Photofrin were required to achieve comparable efficacy in case of intratumoral administration. Also significantly shorter drug-light interval with intratumoral administration can be convenient in the clinical setting, compared to 40-50 h interval required with IV administration to allow drug clearance from the normal tissues. Intratumoral administration also led to more localized drug distribution with minimal skin photosensitivity. In case of IV injection, redness and swelling of the paws and ears was observed as well as increased skin fluorescence at the tumor site and remote sites relating to systemic distribution of the photosensitizer.

 

 

Conclusions:
Intratumoral administration of Photofrin produced similar tumor necrosis as IV administration but with much less photosensitivity side effects. Hence it is strongly supported by this pilot study but warrants further investigations with larger sample sizes and optimization of protocols suitable for clinical use.

 

Related Modulight products and Services

 

Related Publications

Photofrin® photodynamic therapy with intratumor photosensitizer injection provides similar tumor response while reducing systemic skin photosensitivity: Pilot murine study
Timothy M. Baran PhD
Lasers Surg Med., 2018, 50 (5)

 

 

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