Photodynamic therapy of cottontail rabbit papillomavirus-induced papillomas in a severe combined immunodeficient mouse xenograft system.
OBJECTIVE
To evaluate the efficacy of photodynamic therapy (PDT) with the phthalocyanine photosensitizer Pc 4 for treating an animal model of recurrent respiratory papillomatosis (RRP).


METHODS
Rabbit skin was grafted onto the dorsum of severe combined immunodeficient mice, two xenografts per animal. After the graft healed, it was inoculated with cottontail rabbit papillomavirus (CRPV). When papillomas developed, Pc 4 (0.6 or 1.0 mg/kg) was administered systemically, and 48 hours later, one papilloma of the two on each animal was exposed to 675-nm photoactivating light at either 100 or 150 J/cm(2). In addition to the contralateral tumors, which received Pc 4 but no light, other controls included animals receiving light only or neither agent. Response was assessed by measuring papilloma size with a caliper. Some papillomas and residual skin were harvested for histological assessment.


RESULTS
For the lower-dose PDT regimens, papilloma growth rates were not significantly different from the controls. In contrast, 13 of 15 papillomas receiving the higher Pc 4 dose (1.0 mg/kg) and the higher light fluence (150 J/cm(2)) regressed completely and did not regrow within the observation period of up to 79 days. The response of these papillomas was significantly different from the controls (P < .001). Histological analysis confirmed the absence of residual tumor following complete response and replacement with near-normal epithelium.


CONCLUSIONS
Pc 4-PDT is highly effective in treating virally induced (CRPV) papillomas in a murine model of RRP, and thus warrants further study as a treatment for HPV-induced papillomas.
Lee
Richard G
RG
Department of Otolaryngology, Head and Neck Surgery, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Vecchiotti
Mark A
MA
Heaphy
John
J
Panneerselvam
Ashok
A
Schluchter
Mark D
MD
Oleinick
Nancy L
NL
Lavertu
Pierre
P
Alagramam
Kumar N
KN
Arnold
James E
JE
Sprecher
Robert C
RC
D000818:Animals; D012777:Cottontail rabbit papillomavirus; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D010212:Papilloma / Q000188:drug therapy* / Q000821:virology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology; D011817:Rabbits; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000821:virology; D016038:Skin Transplantation; D014183:Transplantation, Heterologous
D007211:Indoles; D017319:Photosensitizing Agents; C107448:phthalocyanine Pc 4