Dataset Information

Irradiance controls photodynamic efficacy and tissue heating in experimental tumours: implication for interstitial PDT of locally advanced cancer.

ABSTRACT:

Background

Currently delivered light dose (J/cm²) is the principal parameter guiding interstitial photodynamic therapy (I-PDT) of refractory locally advanced cancer. The aim of this study was to investigate the impact of light dose rate (irradiance, mW/cm²) and associated heating on tumour response and cure.

Methods

Finite-element modeling was used to compute intratumoural irradiance and dose to guide Photofrin^® I-PDT in locally advanced SCCVII in C3H mice and large VX2 neck tumours in New Zealand White rabbits. Light-induced tissue heating in mice was studied with real-time magnetic resonance thermometry.

Results

In the mouse model, cure rates of 70-90% were obtained with I-PDT using 8.4-245?mW/cm² and ?45?J/cm² in 100% of the SCCVII tumour. Increasing irradiance was associated with increase in tissue heating. I-PDT with Photofrin^® resulted in significantly (p?2 and ?45?J/cm² in 100% of the tumour.

Conclusion

In Photofrin^®-mediated I-PDT, a selected range of irradiance prompts effective photoreaction with tissue heating in the treatment of locally advanced mouse tumour. These irradiances were translated for effective local control of large VX2 tumours.

SUBMITTER: Shafirstein G

PROVIDER: S-EPMC6251027 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Irradiance controls photodynamic efficacy and tissue heating in experimental tumours: implication for interstitial PDT of locally advanced cancer.

Shafirstein Gal G Bellnier David A DA Oakley Emily E Hamilton Sasheen S Habitzruther Michael M Tworek Lawrence L Hutson Alan A Spernyak Joseph A JA Sexton Sandra S Curtin Leslie L Turowski Steven G SG Arshad Hassan H Henderson Barbara B

British journal of cancer 20181024 10

<h4>Background</h4>Currently delivered light dose (J/cm<sup>2</sup>) is the principal parameter guiding interstitial photodynamic therapy (I-PDT) of refractory locally advanced cancer. The aim of this study was to investigate the impact of light dose rate (irradiance, mW/cm<sup>2</sup>) and associated heating on tumour response and cure.<h4>Methods</h4>Finite-element modeling was used to compute intratumoural irradiance and dose to guide Photofrin<sup>®</sup> I-PDT in locally advanced SCCVII in ...[more]

PMID: 30353043

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Project description:PurposePhotodynamic therapy (PDT) using verteporfin was the first pharmacologic therapy for neovascular age-related macular degeneration and changed the treatment paradigm for a major, blinding disease. The experimental work in the nonhuman primate was essential in developing treatment parameters for verteporfin PDT that could successfully occlude choroidal neovascularization with limited injury to the neural retina. Early in the preclinical primate studies, we hypothesized that higher irradiances could be used for ocular PDT than had been used in dermatology and other applications, which typically utilized an irradiance of 150 to 200 mW/cm(2). We set out to test the feasibility of irradiances up to 1800 mW/cm(2).MethodsPDT was applied to normal monkey eyes using verteporfin/benzoporphyrin derivative (BPD) (2 mg/kg) mixed with low-density lipoprotein in DMSO, and 692-nm light, with a spot size 1250mum, fluence approximately 50 J/cm(2), and irradiance varying from 150 (treatment time, 6 minutes) to 1800 mW/cm(2) (treatment time, 30 seconds). Photocoagulation lesions were applied using 514-nm and 692-nm laser light without drug, with irradiance of 18,750 to 200,000 mW/cm(2) and spot size of 500 mum. Treatment effect was evaluated by fundus photography, angiography, and light and electron microscopy with collagen denaturation as a marker of thermal injury.ResultsVerteporfin/BPD PDT at irradiances of 150 to 1800 mW/cm(2) showed no collagen denaturation in contrast to photocoagulation lesions without dye (irradiance 10-fold and higher).ConclusionsVerteporfin PDT could safely be performed at higher irradiances, permitting a clinically practical therapy. Ultimately, clinical trials demonstrated that verteporfin PDT could limit moderate vision loss in neovascular age-related macular degeneration. Although anti-VEGF therapy has replaced PDT as a first-line therapy, PDT may still have a role, perhaps in combination therapies. Further investigations to optimize drug delivery and to better understand the molecular mechanisms of PDT effects in both choroidal neovascularization and retina will improve its application in macular diseases.

Dataset Information

Irradiance controls photodynamic efficacy and tissue heating in experimental tumours: implication for interstitial PDT of locally advanced cancer.

Background

Methods

Results

Conclusion

Publications

Irradiance controls photodynamic efficacy and tissue heating in experimental tumours: implication for interstitial PDT of locally advanced cancer.

Similar Datasets

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