Personalized Oncology by In Vivo Chemical Imaging: Photoacoustic Mapping of Tumor Oxygen Predicts Radiotherapy Efficacy

Abstract

We hereby apply the approach of photoacoustic chemical imaging, performing an in vivo chemical analysis that is spatially resolved (200 μm) and in real time, to predict a given tumor’s response to therapy. Using triple negative breast cancer as a model, we took photoacoustic images of tumors’ oxygen distributions in patient-derived xenografts (PDXs) in mice using biocompatible, oxygen-sensitive tumor-targeted chemical contrast nanoelements (nanosonophores), which function as contrast agents for photoacoustic imaging. Following radiation therapy, we established a quantitatively significant correlation between the spatial distribution of the initial oxygen levels in the tumor and its spatial distribution of the therapy’s efficacy: the lower the local oxygen, the lower the local radiation therapy efficacy. We thus provide a simple, noninvasive, and inexpensive method to both predict the efficacy of radiation therapy for a given tumor and identify treatment-resistant regions within the tumor’s microenvironment.

Nanoprobe-based molecular imaging for tumor stratification

“…143 Recently, Jo et al confirmed the correlation between the initial oxygen levels in tumors and the treatment efficiency in the patient-derived xenograft (PDX) model by using nanosonophores as a photoacoustic contrast agent; a lower the oxygen level before treatment resulted in a worse local radiotherapy effect. 144…”

“…143 Recently, Jo et al confirmed the correlation between the initial oxygen levels in tumors and the treatment efficiency in the patient-derived xenograft (PDX) model by using nanosonophores as a photoacoustic contrast agent; a lower the oxygen level before treatment resulted in a worse local radiotherapy effect. 144 Oxygen partial pressure (PO 2 ) at the tumors can serve as a predictive factor for radiation-related responses. 145 For instance, Zheng et al designed a ratiometric NIR phosphorescent nanoprobe (RHyLI) comprised of semiconducting polymers (PFO-DBT) emitting at 685 nm as an internal reference and phosphorescent emission at 795 nm of a Pd complex capable of reversibly responding to oxygen.…”

A Laser Synthesis Route to Boron‐Doped Gold Nanoparticles Designed for X‐Ray Radiotherapy and Boron Neutron Capture Therapy Assisted by CT Imaging

“…[19,39] XRT sensitization by high-Z elements like Au exploits the emission of photoelectrons, Compton electrons, and Auger electrons after absorption of an X-ray photon, and these types of ionizing radiation can induce cell apoptosis and necrosis by direct damage of DNA or, more frequently, by interaction with water to produce ROS, which is much more easily generated in presence of oxygen. [19,39,44,86] Hence, the XRT potential was tested in vitro in a typical cancer cell model (PC3, human bone metastasis of grade IV prostatic adenocarcinoma). PC3 cells are selected because they are well-known and intensively used for in vitro XRT studies, both in the absence of sensitizers and in the presence of Au NPs or other nano-sensitizers (see Table S1, Supporting Information), thus representing a suitable benchmark for in vitro XRT experiments.…”

“…[4,41] Besides, BNCT is promising for the treatment of hypoxic tumor regions because the alpha particles have high linear energy transfer (LET) and induce direct damage in DNA, causing irreparable double-strand breaks, whereas the low-LET particles produced by XRT induce mostly reparable DNA singlestrand breaks by indirect damage through generation of reactive oxygen species (ROS), resulting more effective on nonhypoxic tumor regions. [4,19,20,24,25,[42][43][44] Thus, an open point concerns the treatment of different regions of the body with the most suited radiation type, after administering a combined sensitizer to the patient. For instance, the possibility to expand the dose-response therapeutic window, minimizing the side effects on healthy tissues, as well as the immunological aspects and the opportunity of stimulating and reinforcing immunotherapy, are all unknown.…”

Phenylboronic Acid‐Modified Near‐Infrared Region II Excitation Donor–Acceptor–Donor Molecule for 2‐Deoxy‐d‐Glucose Improved Starvation/Chemo/Photothermal Combination Therapy

“…[1] Considerable clinical tumor therapies, including surgery, chemotherapy, and radiotherapy have been developed for treating tumors. [2,3] Chemotherapy is the most widely used cancer treatment option because of the high cytotoxicity of drugs such as doxorubicin (DOX), cisplatin, and camptothecin against cancer cells. [4][5][6] However, such cancer treatments still suffer from severe side effects, including damage to healthy cells, drug resistance, and low specificity for cancer cells.…”