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An Animal Model

Lennart A. Lofgren, MD, PhD; Avigdor M. Ronn, PhD; Allan L. Abramson, MD; Mark J. Shikowitz, MD; May Nouri; Catherine J. Lee; James Batti; Bettie M. Steinberg, PhD

Arch Otolaryngol Head Neck Surg. 1994;120(12):1355-1362.

Abstract
Objective
To evaluate the potent photosensitizer m-tetra (hydroxyphenyl) chlorin (m-THPC) by using rabbits with cottontail rabbit papillomavirus–induced tumors and the canine larynx as model systems.

Design
Nonrandomized control trial.

Setting
Division of ear, nose, and throat research at a tertiary care teaching hospital.

Materials
Rabbits were used for relative retention ratio studies and tissue tolerance tests. Studies on the swelling of normal tissues in the larynx after photoactivation were done with canines.

Intervention
Animals were injected with 0.3 mg/kg of m-THPC. At varying intervals, tissues were exposed to 652 nm of light.

Outcome Measures
Outcome measures consisted of four elements: (1) decay of plasma concentration over time, (2) interval to and duration of maximal ratio between drug concentration in normal tissue and tumor, (3) maximal permissible light exposure to normal tissue (skin and laryngeal mucosa) at an optimal interval, and (4) efficacy—number of tumors with partial and complete response.

Results
The largest papilloma to skin ratio (10:1) occurred 4 to 8 days after drug injection. The rabbit skin damage threshold was 40 to 60 J/cm² at 6 days. The canine laryngeal edema and erythema thresholds were 50 to 70 J. A 75% cure rate of papillomas was achieved with tumors that were less than 100 mm² in area at light doses that ranged from 25 to 75 J/cm².

Conclusions
m-THPC shows efficacy in treating papilloma virus–induced tumors. We present a protocol for rapid optimization of the factors required for tumor destruction with minimal normal tissue damage, thus permitting determination of an optimal therapeutic protocol for any photosensitizer.

(Arch Otolaryngol Head Neck Surg. 1994;120:1355-1362)

Author Affiliations
From the Department of Otolaryngology and Communicative Disorders, Long Island Jewish Medical Center, Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, NY.

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