WE-FG-BRA-01: Cancer Treatment Utilizing Photo-Activation of Psoralen with KV X-Rays

Abstract

Purpose: This work investigates X‐PACT (X‐ray Psoralen Activated Cancer Therapy): a new approach for the treatment of cancer. X‐PACT utilizes psoralen, a potent anti‐cancer therapeutic with immunogenic anti‐cancer potential. Psoralen therapies have been limited due to the requirement for psoralen activation by UVA light. X‐PACT solves this challenge by activating psoralen with UV light emitted from novel non‐tethered phosphors (co‐incubated with psoralen) that absorb x‐rays and reradiate (phosphoresce) at UV wavelengths. Methods: The efficacy of X‐PACT was evaluated in both in‐vitro and in‐vivo settings. In‐vitro studies utilized breast (4T1), glioma (CT2A) and sarcoma (KP‐B) cell lines. Cells were exposed to X‐PACT treatments where the concentrations of drug (psoralen and phosphor) and radiation parameters (energy, dose, and dose rate) were varied. Efficacy was evaluated primarily using flow cell cytometry to investigate treatment induced apoptosis. Methylene blue staining, and WST assays were also used. X‐PACT was then evaluated in an in‐vivo pilot study on BALBc mice with syngeneic 4T1 tumors, including control arms for X‐PACT components. Analysis focused on tumor growth delay. Results: A multivariable regression analysis of 36 independent in‐vitro irradiation experiments demonstrated that X‐PACT induces significant tumor cell apoptosis and cytotoxicity on all three tumor cell lines in‐vitro (p<0.0001). Neither psoralen nor phosphor alone had a strongly significant effect. The in‐vivo studies show a pronounced tumor growth delay when compared to controls (42% reduction at 25 days, p=0.0002). Conclusions: These studies demonstrate for the first time a therapeutic effect for X‐PACT, and provide a foundation and rationale for future studies. X‐PACT represents a novel treatment approach in which well‐tolerated low doses of x‐ray radiation generate UVA light in‐situ (including deep seated lesions) which in‐turn photo‐activates powerful anticancer therapeutics which may lead to short and long term therapeutic effect. This work was supported by Immunolight Llc

Utilizing a diagnostic kV imaging system for x-ray psoralen activated cancer therapy (X-PACT)

“…Scaffidi et al used nano-scintillating particles tethered to psoralen to minimize the distance between psoralen and the down-converting scintillator (Scaffidi et al 2011), however tethering limited intercalation of psoralen with DNA thus limiting efficacy. X-PACT utilizes a simplified down-converting system that replaces tethering with co-incubation of psoralen and phosphor particles; this technique benefits from greater intercalation with DNA and utilizes more efficient phosphors with better matched absorption and emission spectra to psoralen (Oldham et al 2016a(Oldham et al , 2016b. While the details of the x-ray source requirements, phosphors, and psoralen activation can be found in a prior publication (Oldham et al 2016a), in summary our prior work shows that X-PACT utilizing an 80 kVp x-ray spectrum can induce cytotoxicity in vitro and a tumor growth delay in BALB/c mice with syngeneic 4T1 tumors.…”

“…Our prior in vitro studies were conducted with dose from the kV source ranging from 0.6 to 2.0 Gy while the BALB/c mouse study utilized a dose of 1 Gy per fraction for six fractions (Oldham et al 2016a(Oldham et al , 2016b. Thus the required dose from the kV source approaches doses and fractionation schemes typically administered in radiotherapy and is considerably higher than diagnostic imaging doses.…”