Direct and Repeated Clinical Measurements of pO2 for Enhancing Cancer Therapy and Other Applications

Abstract

The first systematic multi-center study of the clinical use of EPR oximetry has begun, with funding as a PPG from the NCI. Using particulate oxygen sensitive EPR, materials in three complementary forms (India Ink, "OxyChips", and implantable resonators) the clinical value of the technique will be evaluated. The aims include using repeated measurement of tumor pO2 to monitor the effects of treatments on tumor pO2, to use the measurements to select suitable subjects for the type of treatment including the use of hyperoxic techniques, and to provide data that will enable existing clinical techniques which provide data relevant to tumor pO2 but which cannot directly measure it to be enhanced by determining circumstances where they can give dependable information about tumor pO2.

Keywords: EPR; Hypoxia; Oximetry; Tumor pO2.

Fig. 13.1

(a) Molecular structure of lithium phthalocyanine (LiPc) and lithium octa-n-butoxynaphthalocyanine (LiNc-BuO) oximetry probes. The probes are prepared in the form of fine crystals which are paramagnetic and biologically inert. The crystals exhibit high spin density (~10²⁰ spins/g), single sharp EPR peak (peak-to-peak width <50 mG under anoxic conditions), and are sensitive to oxygen partial pressure of oxygen (5–9 mG/mmHg pO₂). (b) LiNc-BuO crystals, PDMS coating, and the OxyChip. (A) Microcrystals of LiNc-BuO are encapsulated into (B) polydimethylsiloxane (PDMS), a biocompatible and oxygen-permeable polymer, to obtain (C) small pieces of probes (OxyChip) for implantation in tissues. The OxyChip is 0.6 mm in diameter and 5 mm in length and can be conveniently loaded into the tip of an 18-G angio-catheter to be implanted in tumors. (b [B] is reproduced from Courtney 2015 [23])

Fig. 13.2

Implantable resonators for deep-tissue EPR oximetry. The implantable sensors can be made with different length of the transmission line (i.e., depth) that can vary from 1 to >10 cm. Multiple implantable deep-tissue oxygen sensors can be implanted with sensory tips inserted into the tissue of interest and coupling loops positioned under the skin. The external surface loop resonator of the EPR spectrometer is used for inductive coupling to acquire EPR spectra

Fig. 13.3

OxyChips were measured at depths of 1, 7, 13, and 19 mm in lossy material. The peak-to-peak amplitude [V_pp] (left) and estimated linewidth (right) are shown. Consistent linewidths, regardless of depth, establish the capability to measure pO₂ at 2 cm depth in as little as 5 s per measurement. (Error bars are estimated uncertainty in fit parameter, where the oxygen response is ~7 mG/mmHg)