title: PDT dose parameters impact tumoricidal durability and cell death pathways in a 3D ovarian cancer model.
abstract: The successful implementation of photodynamic therapy (PDT)-based regimens depends on an improved understanding of the dosimetric and biological factors that govern therapeutic variability. Here, the kinetics of tumor destruction and regrowth are characterized by systematically varying benzoporphyrin derivative (BPD)-light combinations to achieve fixed PDT doses (M × J cm(-2)). Three endpoints were used to evaluate treatment response: (1) Viability evaluated every 24 h for 5 days post-PDT; (2) Photobleaching assessed immediately post-PDT; and (3) Caspase-3 activation determined 24 h post-PDT. The specific BPD-light parameters used to construct a given PDT dose significantly impact not only acute cytotoxic efficacy, but also treatment durability. For each dose, PDT with 0.25 μM BPD produces the most significant and sustained reduction in normalized viability compared to 1 and 10 μM BPD. Percent photobleaching correlates with normalized viability for a range of PDT doses achieved within BPD concentrations. To produce a cytotoxic response with 10 μM BPD that is comparable to 0.25 and 1 μM BPD a reduction in irradiance from 150 to 0.5 mW cm(-2) is required. Activated caspase-3 does not correlate with normalized viability. The parameter-dependent durability of outcomes within fixed PDT doses provides opportunities for treatment customization and improved therapeutic planning.
authors: Wellman Center for Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: Imran
authors: I
authors: Rizvi
authors: Sriram
authors: S
authors: Anbil
authors: Nermina
authors: N
authors: Alagic
authors: Jonathan
authors: J
authors: Celli
authors: Jonathan P
authors: JP
authors: Celli
authors: Lei Zak
authors: LZ
authors: Zheng
authors: Akilan
authors: A
authors: Palanisami
authors: Michael D
authors: MD
authors: Glidden
authors: Brian W
authors: BW
authors: Pogue
authors: Tayyaba
authors: T
authors: Hasan
mesh_terms: D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D002470:Cell Survival; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000628:therapy*; D010778:Photochemotherapy / Q000295:instrumentation*; D011166:Porphyrins / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D000077362:Verteporfin
chemical_list: D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D000077362:Verteporfin; D053148:Caspase 3