Photodynamic therapy of human choriocarcinoma transplanted to the hamster cheek pouch. II. Intra-lesional photosensitization.
Photodynamic therapy (PDT) uses light-activated compounds, such as hematoporphyrins, to produce cytotoxic effects after illumination. Human choriocarcinoma cells were transplanted into the hamster cheek pouch to study PDT. The transplanted choriocarcinoma secretes human chorionic gonadotropin (hCG) in proportion to tumor volume. Red light (630 nm) from an argon-pumped dye laser (100-200 J/cm2) was used to illuminate tumors sensitized with dihematoporphyrin ether (DHE). Previous work has demonstrated complete regression (CR) of 90% of tumors (18/20) after one or two PDT sessions, while contralateral cheek pouch tumors continued to grow despite intraperitoneal DHE. Neither DHE nor laser light alone resulted in significant CRs. In this study we evaluated intratumoral injection of DHE followed in 2 hr by laser treatment. In all tumors, localization of DHE was demonstrated by induced fluorescence with ultraviolet light or He:Cd laser. After a single treatment, 14 of 38 tumors (37%) completely regressed (hCG less than mIU/ml); 4 tumors regressed grossly with low-level hCG [partial regression (PR)]. After repeat treatment there were 10 additional CRs in 19 rapidly enlarging tumors. After a third treatment 3 CRs and 3 PRs were achieved in 6 tumors. Because of large volumes, 2 of 3 progressing tumors failed to fluoresce uniformly after intratumoral DHE and were treated after intraperitoneal DHE injection; both completely responded. Overall, 29 of 38 tumors (76%) completely responded to PDT, and 7 partially responded (18%) with no gross tumor remaining in 5 of the 7. Only 5% of tumors (2/38) were non-responders. Photodynamic therapy results in gross elimination of 90% of tumors (52/58) in this model after intraperitoneal or intratumoral DHE sensitization (P less than 0.0001). DHE in chorio-carcinomas is easily detected and may enable detection of occult foci of malignancy. Choriocarcinoma transplanted into the hamster cheek pouch is highly responsive to photodynamic therapy. Clinical trials of PDT in gynecologic cancers are warranted to confirm the high response rates observed in refractory nongynecologic cancers.
Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, California 90048.
E
E
Brand
H S
HS
Choi
G D
GD
Braunstein
W S
WS
Grundfest
L D
LD
Lagasse
D000818:Animals; D002610:Cheek; D002822:Choriocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006063:Chorionic Gonadotropin / Q000097:blood; D006224:Cricetinae; D005260:Female; D006801:Humans; D008647:Mesocricetus; D009336:Necrosis; D009368:Neoplasm Transplantation; D010778:Photochemotherapy; D012074:Remission Induction
D006063:Chorionic Gonadotropin