Photodynamic therapy using m-tetra(hydroxyphenyl) chlorin. An animal model.
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.


METHODS
Nonrandomized control trial.


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


METHODS
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.


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


METHODS
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.
Lofgren
L A
LA
Department of Otolaryngology and Communicative Disorders, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, NY.
Ronn
A M
AM
Abramson
A L
AL
Shikowitz
M J
MJ
Nouri
M
M
Lee
C J
CJ
Batti
J
J
Steinberg
B M
BM
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002985:Clinical Protocols; D012777:Cottontail rabbit papillomavirus; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D016903:Drug Monitoring; D007822:Laryngeal Neoplasms / Q000097:blood / Q000188:drug therapy*; D008652:Mesoporphyrins / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D030361:Papillomavirus Infections / Q000097:blood / Q000188:drug therapy*; D010778:Photochemotherapy / Q000009:adverse effects / Q000379:methods*; D011817:Rabbits; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy*; D013997:Time Factors; D014412:Tumor Virus Infections / Q000097:blood / Q000188:drug therapy*
D000970:Antineoplastic Agents; D008652:Mesoporphyrins; C072269:temoporfin