Molecular MRI-Based Monitoring of Cancer Immunotherapy Treatment Response

Abstract

Immunotherapy constitutes a paradigm shift in cancer treatment. Its FDA approval for several indications has yielded improved prognosis for cases where traditional therapy has shown limited efficiency. However, many patients still fail to benefit from this treatment modality, and the exact mechanisms responsible for tumor response are unknown. Noninvasive treatment monitoring is crucial for longitudinal tumor characterization and the early detection of non-responders. While various medical imaging techniques can provide a morphological picture of the lesion and its surrounding tissue, a molecular-oriented imaging approach holds the key to unraveling biological effects that occur much earlier in the immunotherapy timeline. Magnetic resonance imaging (MRI) is a highly versatile imaging modality, where the image contrast can be tailored to emphasize a particular biophysical property of interest using advanced engineering of the imaging pipeline. In this review, recent advances in molecular-MRI based cancer immunotherapy monitoring are described. Next, the presentation of the underlying physics, computational, and biological features are complemented by a critical analysis of the results obtained in preclinical and clinical studies. Finally, emerging artificial intelligence (AI)-based strategies to further distill, quantify, and interpret the image-based molecular MRI information are discussed in terms of perspectives for the future.

AI in MRI: Computational Frameworks for a Faster, Optimized, and Automated Imaging Workflow

“…AI has been found useful, for example, for the diagnosis of breast and prostate cancer from MRI [ 79 , 80 ], the diagnosis of COVID-19 from medical images [ 81 , 82 ], and fault detection in health management [ 83 ]. Furthermore, AI-based methods have led to state-of-the-art results in lesion detection and classification [ 84 , 85 , 86 , 87 , 88 ].…”

Monitoring Melanoma Responses to STING Agonism and Focused Ultrasound Thermal Ablation Using Microneedles and Ultrasensitive Single Molecule Arrays

“…[91][92][93] To date, multiple methods have been proposed with predictive or prognostic value in the context of immunotherapy monitoring. These include the measurement of biomarkers such as mutational load or PD-L1 expression, plasma analysis of cells, [94,95] tumor exosomes, [15,96] and biomarkers such as soluble PD-L1 (sPD-L1), [97,98] S100B and LDH, [10] ctDNA, cfRNA, and cmiRNA, [15,16] cytokines, [99] molecular imaging techniques studying growth and response of tumors, [100,101] and microbiota analysis. [102,103] While these methods provide clinically significant information in the context of patient stratification, their clinical adoption may be suboptimal due to their invasive nature, associated costs, and the low sensitivity for biomarkers that are diluted in the circulating blood.…”

Recent Advances in the Development of Non‐Invasive Imaging Probes for Cancer Immunotherapy

“…Several platforms of molecular imaging including magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), computed tomogra-phy (CT), optical imaging (OI), and ultrasound (US) are being utilized in the laboratory and clinical settings, each having their own advantages and limitations. [22][23][24][25][26][27][28] Recently, a structure-inherent targeting (SIT) strategy that uses nearinfrared (NIR) fluorophores [29] with different cell/tissue specificities driven by their inherent chemical structures has also been explored to target tumor-associated immune cells without conjugation of targeting moieties. [30][31] In the following sections, we discuss recent advances in the development of imaging tools divided into two categories -affinity-based and substrate/activity-based probesdetailing main structural components and imaging modalities with example cases that best illustrate their biological and clinical applications.…”

“…Reporter tags allow to localize, visualize, and quantify the signal readout and play a critical role in achieving optimal in vivo pharmacokinetic properties. Several platforms of molecular imaging including magnetic resonance imaging (MRI), positron emission tomography (PET), single‐photon emission computed tomography (SPECT), computed tomography (CT), optical imaging (OI), and ultrasound (US) are being utilized in the laboratory and clinical settings, each having their own advantages and limitations [22–28] . Recently, a structure‐inherent targeting (SIT) strategy that uses near‐infrared (NIR) fluorophores [29] with different cell/tissue specificities driven by their inherent chemical structures has also been explored to target tumor‐associated immune cells without conjugation of targeting moieties [30–31] …”