Contrast Agent For Photoacoustic Imaging Research Articles

Engineering the Blackbody Absorption of the Au-Branch-on-Au-Plate Heterostructures.

Utilizing the strong ligand control effects of l-cysteine (l-Cys), the growth of Au on Au triangular nanoplate (AuTN) seeds was continuously tuned from layer-by-layer (the Frank-van der Merwe) to layer-plus-island (the Stranski-Krastanov), and island (the Volmer-Weber) growth modes, leading to the formation of a series of Au-on-AuTN heterostructures. Within the window of VW growth mode (featured by the growth of Au spikes and branches on AuTNs), the effective localized surface plasmon resonance (LSPR) coupling led to the selective strengthening of the "valley" absorptions, leading to smooth and flat absorption curves. Interestingly, through engineering the number/density, size, and branching degree of the Au branches, except for the black color, full spectrum absorption within 400-1300 nm wavelength was achieved on Au-branch-on-AuTN structures. Mechanistic studies revealed that the blackbody absorption property of the Au-branch-on-AuTN originates from the well-balanced intraparticle LSPR couplings among the neighboring Au branches. The tunable blackness and the full spectrum absorption property made the Au-branch-on-AuTN heterostructure a suitable candidate for various plasmonic-related applications, such as a wide spectrum light absorber, photoacoustic imaging contrast agent, and photothermal therapy medium. In addition, our strong ligand control in Au-branch-on-AuTN heterostructures could be extended to other hybrid systems with diverse material combinations, so long as to find the proper strong ligand.

Coupling Gold Nanospheres into Nanochain Constructs for High-Contrast, Longitudinal Photoacoustic Imaging.

Structural parameters play a crucial role in determining the electromagnetic and thermal responses of gold nanoconstructs (GNCs) at near-infrared (NIR) wavelengths. Therefore, developing GNCs for reliable, high-contrast photoacoustic imaging has been focused on adjusting structural parameters to achieve robust NIR light absorption with photostability. In this study, we introduce an efficient photoacoustic imaging contrast agent: gold sphere chains (GSCs) consisting of plasmonically coupled gold nanospheres. The chain geometry results in enhanced photoacoustic signal generation originating from outstanding photothermal characteristics compared to traditional gold contrast agents, such as gold nanorods. Furthermore, the GSCs produce consistent photoacoustic signals at laser fluences within the limits set by the American National Standards Institute. The exceptional photoacoustic response of GSCs allows for high-contrast photoacoustic imaging over multiple imaging sessions. Finally, we demonstrate the utility of our GSCs for molecular photoacoustic cancer imaging, both in vitro and in vivo, through the integration of a tumor-targeting moiety.

Integrated drug delivery system loading ROS-generating antitumor drugs for signal-amplified photoacoustic imaging and multimodal tumor therapy

The usefulness of antitumor drugs that produce reactive oxygen species (ROS) in accurate tumor diagnosis and treatment has been underestimated. Here, β-Lapachone (Lapa, antitumor drugs), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS, precursor photoacoustic agents) and 2, 2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH, free radical initiators) were successfully loaded into zeolitic imidazolate framework (ZIF) in situ by a one-pot method and named Lapa/ABTS/AIPH@ZIF-67 nanoparticles (LBIZ NPs). After entering the tumor cell, the ZIF structure of LBIZ NPs is disrupted in the acidic tumor microenvironment, which results in the release of Co2+ and drugs. In one hand, Lapa and Co2+ together increased hydroxyl radicals (•OH) levels to achieve Enhanced-Chemodynamic therapy (ECDT). As the amount of •OH went up, the amount of ABTS•+, the oxidation product of ABTS, would also increase, thus increasing the sensitivity and contrast of photoacoustic imaging. In the other hand, the photothermal effect produced by ABTS•+ induces AIPH to crack and release alkyl radicals (•R) to achieve thermodynamic therapy. The LBIZ NPs achieved more effective tumor treatments by fully utilizing light and heat energy. Hence, this integrated drug delivery system is able to achieve signal-amplified photoacoustic imaging and Enhanced-Chemodynamic/Photothermal/Thermodynamic trimodal combination therapy. This work provides a new insight into the application of ROS-generating antitumor drugs to precise imaging of tumors.

Semiconducting Polymers Based on Asymmetric Thiadiazoloquinoxaline for Augmented In Vivo NIR-II Photoacoustic Imaging.

A photoacoustic (PA) imaging technique using the second near-infrared (NIR-II) window has attracted more and more attention because of its merits of deeper penetration depth and higher signal-to-noise (S/N) ratio than that using the first near-infrared (NIR-I) one. However, the design and development of high-performance PA imaging contrast agents in the NIR-II window is still a challenge. A semiconducting polymer, constructed by asymmetric units, exhibits regiorandom characteristics that effectively increase the distortion of the backbone. This increase in the degree of twist can regulate the twisted intramolecular charge transfer (TICT) effect, resulting in an enhancement of the PA signal. In this paper, an asymmetric structural acceptor strategy is developed to improve the PA signals of the resulting semiconducting polymer (PATQ-MP) in the NIR-II window with improved brightness, higher S/N ratio, and better photothermal conversion efficiency compared to polymers with the same main-chain structure containing a symmetric acceptor. DFT analysis showed that PATQ-MP containing an asymmetric acceptor monomer had a larger dihedral angle, which effectively improved the PA signal intensity by enhancing the TICT effect. The PEG-encapsulated PATQ-MP nanoparticles exhibit promising performance in the PA imaging of mouse tumors in vivo, demonstrating the clear identification of microvessels as small as 100 μm along with rapid metabolism within a span of 5 h. Therefore, this work provides a unique molecular design strategy for improving the signal intensity of PA imaging in the NIR-II window.

Photoacoustic Imaging of Human Skin for Accurate Diagnosis and Treatment Guidance

Photoacoustic imaging (PAI) is a cutting-edge biomedical imaging modality, providing detailed anatomical and functional information about the area beneath the skin surface. Its light energy deposition is such that PAI typically provides clear images of the skin with high signal-to-noise ratios. Specifically, the rich optical contrast of PAI allows biological information related to lesion growth, malignancy, treatment response, and prognosis to be seen. Given its significant advantages and emerging role in imaging skin lesions, we summarize and comment on representative studies of skin PAI, such as the guidance of skin cancer biopsies and surgical excisions, and the accurate diagnosis of psoriasis. We conclude with our insights about the clinical significance of skin PAI, showing how its use to identify biological characteristics in lesion microenvironments allows early diagnosis and prognosis of disease.

Regulating interparticle proximity in plasmonic nanosphere aggregates to enhance photoacoustic response and photothermal stability.

Designing plasmonic nanoparticles for biomedical photoacoustic (PA) imaging involves tailoring material properties at the nanometer scale. A key in developing plasmonic PA contrast nanoagents is to engineer their enhanced optical responses in the near-infrared wavelength range, as well as heat transfer properties and photostability. This study introduces anisotropic plasmonic nanosphere aggregates with close interparticle proximity as photostable and efficient contrast agent for PA imaging. Silver (Ag), among plasmonic metals, is particularly attractive due to its strongest optical response and highest heat conductivity. Our results demonstrate that close interparticle proximity in silver nanoaggregates (AgNAs), spatially confined within a polymer shell layer, leads to blackbody-like optical absorption, resulting in robust PA signals through efficient pulsed heat generation and transfer. Additionally, our AgNAs exhibit a high photodamage threshold highlighting their potential to outperform conventional plasmonic contrast agents for high-contrast PA imaging over multiple imaging sessions. Furthermore, we demonstrate the capability of the AgNAs for molecular PA cancer imaging in vivo by incorporating a tumor-targeting peptide moiety.

Mn(iii), Fe(iii) and Zn(ii)-serum albumin as innovative multicolour contrast agents for photoacoustic imaging.

Here we propose innovative photoacoustic imaging (PAI) contrast agents, based on the loading of Mn(iii)-, Fe(iii)- or Zn(ii)-protoporphyrin IX in serum albumin. These systems show different absorption wavelengths, opening the way to multicolor PA imaging. They were characterized in vitro for assessing stability, biocompatibility, and their optical and contrastographic properties. Finally, a proof of concept in vivo study was carried out in breast cancer bearing mice, to evaluate its effectiveness for cancer imaging.

A reductively convertible nickel phthalocyanine precursor as a biological thiol-responsive turn-on photoacoustic contrast agent.

A nickel phthalocyanine precursor bearing poly(ethylene glycol) as a turn-on contrast agent for photoacoustic imaging was prepared. The water-soluble polymeric chains were smoothly eliminated through thiol-mediated reductive aromatization in cancer cells, enabling the detection of endogenous biological thiols in vitro and in vivo.

Contrast enhanced photoacoustic detection of fibrillar collagen in the near infrared region-I.

Fibrillar collagen accumulation emerges as a promising biomarker in several diseases, such as desmoplastic tumors and unstable atherosclerotic plaque. Gold nanorods (GNRs) hold great potential as contrast agents in high-resolution, biomedically safe, and non-invasive photoacoustic imaging (PAI). This study presents the design and characterization of a specialized imaging tool which exploits GNR assisted targeted photoacoustic imaging that is tailored for the identification of fibrillar collagen. In addition to the photoacoustic characterization of collagen in the NIR 1 and 2 regions, we demonstrate the detailed steps of conjugating a decoy to GNRs. This study serves as a proof of concept, that demonstrates that conjugated collagenase-1 (MMP-1) generates a distinct and collagen-specific photoacoustic signal, facilitating real-time visualization in the wavelength range of 700-970 nm (NIR I). As most of the reported studies utilized the endogenous contrast of collagen in the NIR II wavelength that has major limitations to perform in vivo deep tissue imaging, the approach that we are proposing is unique and it highlights the promise of MMP-1 decoy-functionalized GNRs as novel contrast agents for photoacoustic imaging of collagen in the NIR 1 region. To our knowledge this is the first time functionalized GNRs are optimized for the detection of fibrillar collagen and utilized in the field of non-invasive photoacoustic imaging that can facilitate a better prognosis of desmoplastic tumors and broken atherosclerotic plaques.

Enhancing tissue imaging contrast in photoacoustic tomography using the ultrasound thermal effect.

Photoacoustic imaging is a powerful technique for obtaining high-resolution images of vascular distribution and physiological information about blood by utilizing the light absorption coefficient as an imaging contrast. However, visualizing weakly light-absorbing components without specific contrast agents or multi-wavelength techniques presents a challenge due to significant differences in light absorption between these components and blood. In this study, we propose a novel method that leverages the thermal effect of ultrasound to induce temperature differences and enhance the contrast of photoacoustic imaging. We conducted phantom experiments to verify the feasibility of our method. Our method effectively highlighted weakly light-absorbing components with strong acoustic absorption, even in the presence of highly light-absorbing components such as blood or melanin. Furthermore, it enabled the differentiation of components with similar light absorption but different acoustic absorption.

Hyper-Branched Gold Nanoconstructs for Photoacoustic Imaging in the Near-Infrared Optical Window.

In plasmonic nanoconstructs (NCs), fine-tuning interparticle interactions at the subnanoscale offer enhanced electromagnetic and thermal responses in the near-infrared (NIR) wavelength range. Due to tunable electromagnetic and thermal characteristics, NCs can be excellent photoacoustic (PA) imaging contrast agents. However, engineering plasmonic NCs that maximize light absorption efficiency across multiple polarization directions, i.e., exhibiting blackbody absorption behavior, remains challenging. Herein, we present the synthesis, computational simulation, and characterization of hyper-branched gold nanoconstructs (HBGNCs) as a highly efficient PA contrast agent. HBGNCs exhibit remarkable optical properties, including strong NIR absorption, high absorption efficiency across various polarization angles, and superior photostability compared to conventional standard plasmonic NC-based contrast agents such as gold nanorods and gold nanostars. In vitro and in vivo experiments confirm the suitability of HBGNCs for cancer imaging, showcasing their potential as reliable PA contrast agents and addressing the need for enhanced imaging contrast and stability in bioimaging applications.

Machine learning assisted designing of Indacenodithiophene (IDT)-based polymers for future application of photoacoustic imaging

Non-invasive imaging tools are essential for diagnosis of complex disease. Photoacoustic (PA) imaging is a multiscale noninvasive imaging modality with high resolution and sensitivity for deep-seated pathologies. However, microenvironment of some pathologies produce PA signals compromising the optical resolution of PA imaging. This demands the construction of PA imaging agents to avoid the low signal to noise ratio with improved resolution and sensitivity. In this study, we use machine learning to design the IDT-based polymers with their absorption coefficient in NIR-I region. We used the database of polymer structures and properties to identify promising candidates for PAI. The models were then used to predict the properties of new IDT-based polymers with optimized absorption, biocompatibility and acoustic performance. Several promising candidates were identified and their in silico synthesis potential and PA imaging performance was predicted. The results demonstrates the potential of machine learning-guided polymers design for PA imaging agents and suggest that IDT-based polymers could be a valuable addition to the toolkit of PA imaging contrast agents.

A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5β1-targeted gold nanorods

BackgroundEarly detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments.ResultsIn an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRs@PEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism.ConclusionGNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions.Graphical

Numerical investigation on improving photoacoustic imaging contrast based on temperature difference effect in biological tissues

Exploiting the variances in light absorption among different components of biological tissues and utilizing the light absorption coefficient as an imaging contrast, photoacoustic imaging achieves remarkable imaging resolution. Within the laser wavelength range commonly employed in photoacoustic imaging, biological tissue components like hemoglobin and melanin exhibit higher light absorption coefficients compared to other components. Consequently, these components generate stronger photoacoustic signals during the imaging process. However, this heightened signal strength obscures components of biological tissues with low light absorption coefficients, making it challenging to clearly visualize them in the resulting images. To address this limitation and enhance the visibility of low absorption coefficient components against a background of intense photoacoustic signals produced by high absorption coefficient components, we propose a method that utilizes low-intensity unfocused ultrasound to induce the temperature difference (TD) effect in biological tissues during photoacoustic imaging. By analyzing the disparities between the photoacoustic signals collected before and after introducing the TD effect, we establish a novel imaging parameter that improves the imaging contrast. To validate the feasibility and effectiveness of inducing photoacoustic effects in biological tissues, we conducted simulations using the finite element method, which yielded positive results. Subsequent simulations of photoacoustic imaging incorporating the TD effect demonstrated enhanced visualization of components with low light absorption coefficients in biological tissue. The method proposed in this paper is expected to provide a research idea for improving the photoacoustic imaging contrast of biological tissues.

EGFR-targeted semiconducting polymer nanoparticles for photoacoustic imaging

Semiconducting polymer nanoparticles (SPN), formulated from organic semiconducting polymers and lipids, show promise as exogenous contrast agents for photoacoustic imaging (PAI). To fully realise the potential of this class of nanoparticles for imaging and therapeutic applications, a broad range of active targeting strategies, where ligands specific to receptors on the target cells are displayed on the SPN surface, are urgently needed. In addition, effective strategies for quantifying the level of surface modification are also needed to support development of ligand-targeted SPN. In this paper, we have developed methods to prepare SPN bearing peptides targeted to Epidermal Growth Factor Receptors (EGFR), which are overexpressed at the surface of a wide variety of cancer cell types. In addition to fully characterising these targeted nanoparticles by standard methods (UV–visible, photoacoustic absorption, dynamic light scattering, zeta potential and SEM), we have developed a powerful new NMR method to determine the degree of conjugation and the number of targeting peptides attached to the SPN. Preliminary in vitro experiments with the colorectal cancer cell line LIM1215 indicated that the EGFR-targeting peptide conjugated SPN were either ineffective in delivering the SPN to the cells, or that the targeting peptide itself destabilised the formulation. This in reinforces the need for effective characterisation techniques to measure the surface accessibility of targeting ligands attached to nanoparticles.

Copper Sulfide Small Nanoparticles as Efficient Contrast Agent for Photoacoustic Imaging

An experimental study on an innovative contrast agent is presented. This work demonstrates that copper sulfide in the form of small-sized nanoparticles can be exploited in photoacoustic imaging. An advantage of this material is strong light absorption in the near-infrared range, especially in the transparency windows of biological tissues. In order to yield a proper contrast, light absorption must be followed by heat release with high efficiency. Therefore, it is important to evaluate the photochemical conversion efficiency of the material. We applied a method that is strictly related to photoacoustic applications. The nanoparticles were produced according to a well-established synthesis. Subsequently, they were diluted in pure water to obtain an extinction <0.2/cm at 1064 nm. The photoacoustic signals, generated by 1064 nm laser excitation, were analyzed as a function of concentration and incident laser energy below 70 μJ /pulse. The signals were carefully compared with those of a reference aqueous solution, containing a light-absorbing ionic solute. Data analysis yielded a light-to-heat conversion efficiency 1.0 (±0.1). We discuss this result by comparison with related studies on other types of copper sulfide nanoparticles, where the conversion efficiency reportedly varied from 33% to 93%. The high value determined in the present study possibly indicates that resonant light scattering and luminescence are negligible for our material system.

Cooperative phototherapy based on bimodal imaging guidance for the treatment of uveal melanoma

BackgroundUveal melanoma (UM) is adults’ most common primary intraocular malignant tumor, prone to metastasis and high mortality. Eyeball enucleation commonly used in the clinic will lead to permanent blindness and mental disorders. Thus, new methods are urgently needed to diagnose and treat UM early to preserve patients’ vision.Methods and resultsHerein, multifunctional nanoparticles (NPs) were synthesized by loading chlorin e6 (Ce6) in poly-lactic-co-glycolic acid (PLGA) NPs and wrapping FeIII-tannic acid (FeIII-TA) on the outside (FeIII-TA/PLGA/Ce6, designated as FTCPNPs). Then, the synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) antitumor effects of FTCPNPs excited by near-infrared (NIR) laser were evaluated. Moreover, we verified the mechanism of synergistic PTT/PDT leading to mitochondrial dysfunction and inducing tumor cell apoptosis. Additionally, FTCPNPs can be used as excellent magnetic resonance (MR)/photoacoustic (PA) imaging contrast agents, enabling imaging-guided cancer treatment. Finally, The NPs have good biological safety.ConclusionThis noninvasive NIR light-triggered cooperative phototherapy can easily penetrate eye tissue and overcome the disadvantage of limited penetration of phototherapy. Therefore, cooperative phototherapy is expected to be used in fundus tumors. This treatment model is applied to UM for the first time, providing a promising strategy and new idea for integrating the diagnosis and treatment of UM.

Folate Receptor‐Targeted NIR‐II Dual‐Model Nanoprobes for Multiscale Visualization of Macrophages in Rheumatoid Arthritis

AbstractRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation. Macrophages accelerate the pathological process of RA through the continuous cell accumulation and secretion of cytokines. Therefore, multiscale visualization of macrophages is of great significance for the early diagnosis of RA. In this work, folate receptor‐targeted Cptnc‐4F nanoprobes, named FA‐CF‐NPs, are developed for dual‐model molecular imaging of macrophages in RA mouse models. FA‐CF‐NPs exhibit complementary imaging advantages with high fluorescence sensitivity and resolution in the second near‐infrared window (NIR‐II) and promising photoacoustic (PA) imaging contrast with deep tissue penetration. The high affinity of the folate ligand on the surface of FA‐CF‐NPs to macrophages with overexpressed folate receptors ensures the specific targeting function of the nanoprobes for imaging in vivo. FA‐CF‐NPs are employed to achieve NIR‐II fluorescence imaging to accurately localize macrophages in the joint, obtaining a high signal‐to‐background ratio (SBR) of 15.5. Meanwhile, PA imaging is also performed to observe macrophage distribution in the longitudinal section of the whole joint. Moreover, macrophage infiltration is detected in the joint of RA mice with the absence of RA pathologies such as synovitis and cartilage loss. The results provide an opportunity for in vivo macrophage tracking and early diagnosis of RA.

Abstract 2381: Gold nanorods functionalized with an alpha5beta1 ligand: a simple and robust nanosystem for early bladder cancer detection

Abstract Early detection and removal of bladder cancer (BC) is crucial to prevent tumor recurrence and progression. Various imaging modalities have been used to diagnose BC, including computed tomography urography, intravenous urography, ultrasound echography, multiparametric magnetic resonance imaging, cystoscopy, and cystoscopy in conjunction with intravesical instillation of hexaminolaevulinic acid, a photodynamic diagnostic agent. However, all these imaging techniques show a very poor detection rate of small (<5mm) and flattened cancer lesions. Because of this limitation, patients with BC frequently relapse after initial diagnosis and need frequent follow-ups and treatments, resulting in a poor quality of life. For the same reason, BC has the highest cost/patient among all cancers. We have recently developed a new methodology to detect bladder cancer lesions based on bladder instillation with GNRs@Chit-Iso4, a nanosystem consisting of gold nanorods (GNRs) decorated with chitosan and functionalized with the head-to-tail cyclized [CphgisoDGRG] peptide (Iso4, a selective ligand of alpha5beta1-integrin expressed by BC cells), followed by low-frequency ultrasound-assisted shaking of nanoparticles necessary to prevent their sedimentation, and photoacoustic imaging of targeted tumor lesions. In murine models, this procedure can detect orthotopic BC lesions <0.5 mm, undetectable by standard imaging modalities (Alchera et al., Photoacoustic, 2022). In the attempt to develop a simpler and more effective imaging modality of BC, we have produced and preclinically evaluated new GNRs decorated with lipoic acid-polyethylene glycol (PEG -5KDa) and functionalized with Iso4. The resulting product, obtained by a simple 2-step procedure and called GNRs@PEG5K-Iso4, efficiently recognized alpha5beta1- and alpha5beta1-expressing cells, was stable in 90% urine, and was resistant to freezing- or salt-induced aggregation.GNRs@PEG5K-Iso4 did not undergo sedimentation after instillation into the bladder, thereby avoiding the need of the complex ultrasound-assisted shaking of nanoparticles and could efficiently detect BC lesions smaller than <0.5 mm in murine models. These results suggest that GNRs@PEG5K-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and early diagnosis of small BC lesions. Citation Format: Massimo Alfano, Elisa Alchera, Angelina Sacchi, Alessandro Gori, Irene Locatelli, Anna Maria Gasparri, Barbara Colombo, Giulia Anderluzzi, Paolo Armanetti, Luca Minichetti, Andrea Salonia, Angelo Corti, Flavio Curnis. Gold nanorods functionalized with an alpha5beta1 ligand: a simple and robust nanosystem for early bladder cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2381.

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

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.