Postirradiation hyperthermia selectively potentiates the merocyanine 540-sensitized photoinactivation of small cell lung cancer cells

Lung cancer has long been considered a disease that might benefit from the dose escalation of radio/chemotherapy afforded by a stem cell transplant. H owever, the clinical experience with high-dose chemotherapy and autologous bone marrow transplantation in lung cancer has been disappointing, with mos t trials showing little or no improvement in long-term survival. Unfortunat ely, lung cancer has a tendency to metastasize to the bone marrow, and lung cancer cells are known to circulate in the peripheral blood. Therefore, th ere is concern that autologous stem cell grafts from lung cancer patients m ay reinoculate recipients with live tumor cells. Photochemical purging of s tem cell grafts with Merocyanine 540 (MC540) is highly effective against a wide range of leukemia and lymphoma cells and is well tolerated by normal h ematopoietic stem and progenitor cells. Most solid tumor cells (including l ung cancer cells), however, are only moderately sensitive or refractory to MC540-mediated photodynamic therapy (PDT), We report here that postirradiat ion hyperthermia (less than or equal to 42 degreesC, 3 h) potentiates the M C540-mediated photoinactivation of both wild-type (H69) and cisplatin-resis tant mutant (H69/CDDP) small cell lung cancer cells by several orders of ma gnitude, while only minimally enhancing the depletion of normal human granu locyte/macrophage progenitor cells. Our data suggest that postirradiation h yperthermia provides a simple and effective means of extending the utility of MC540-PDT to the purging of stem cell grafts contaminated with lung canc er and possibly other solid tumor cells.