Abstract
Photoimmunotherapy (PIT) is a cell-specific cancer therapy based on an armed antibody conjugate that induces rapid and highly selective cancer cell necrosis after exposure to near-infrared (NIR) light. The PIT treatment also induces the superenhanced permeability and retention effect, which allows high concentrations of nanoparticles to accumulate in the tumor bed. In our pilot studies, optical coherence tomography (OCT) reveals dramatic hemodynamic changes during PIT. We developed and applied speckle variance analysis, Doppler flow measurement, bulk motion removal, and automatic region of interest selection to quantify vessel diameter and blood velocity within tumors in vivo. OCT imaging reveals that blood velocity in peripheral tumor vessels quickly drops below the detection limit while the vessel lumen remains open (4 vessels from 3 animals). On the other hand, control tumor vessels (receive NIR illumination but no PIT drug) do not show the sustained blood velocity drop (5 vessels from 3 animals). Ultraslow blood velocity could result in a long drug circulation time in tumor. Increase of the blood pool volume within the central tumor (shown in histology) may be the leading cause of the periphery blood velocity drop and could also increase the drug pool volume in tumor vessels.
Highlights
Photoimmunotherapy (PIT) is a cell-specific cancer therapy with minimal side effects, which is based on an armed antibody conjugate that induces rapid cellular necrosis after exposure to near-infrared (NIR) light
It has been hypothesized that the selective destruction of the perivascular layers of cancer cells by PIT leads to expansion of the tumor vessel diameter and results in a 24-fold increase in the accumulation of various nanomaterials in the tumor bed
Doppler OCT (DOCT) provides the blood velocity information and speckle variance (SV) provides the size of the open lumen
Summary
Photoimmunotherapy (PIT) is a cell-specific cancer therapy with minimal side effects, which is based on an armed antibody conjugate that induces rapid cellular necrosis after exposure to near-infrared (NIR) light. When exposed to NIR light, the conjugate induces highly selective and rapid cancer cell death both in vitro and in vivo.[1,2] It has been hypothesized that the selective destruction of the perivascular layers of cancer cells by PIT leads to expansion of the tumor vessel diameter and results in a 24-fold increase in the accumulation of various nanomaterials in the tumor bed. This effect is most marked for nanosized molecules including nanoscale anti-cancer drugs and reflects a relative increase in the permeability of vessels for larger molecules.[3] This effect has been termed superenhanced permeability and retention (SUPR) to differentiate it from the more modest-enhanced permeability and retention that is commonly seen in tumors. Little is known about the specific effects of PIT on vessel size and blood flow changes at a microscopic
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