![]() ![]() 20Ģ.1 Chemotherapeutic Agents in Oncology. 18Ĭhapter 2 Visualizing Tumor Mutational Burden: Development of Radioligands for PD-L1. 18ġ.3 Collaborative Multidisciplinary Science. ![]() Table of Contentsġ.2 Manipulation of chemical properties to better interrogate biological systems. Based on a PD-L1 binding small molecule, this radiotracer is easy to synthesize and selectively binds to PD-L1 with nanomolar potency. Herein we describe the design, synthesis, and optimization of a PET tracer to visualize PD-L1 mutational status. This technology, aided by a radiotracer such as 18F-fluorodeoxyglucose, allows oncologists to visualize the tumors in their patients and with modern mutation- or protein-specific tracers, allows clinicians to formulate treatment plans. Positron emission tomography (PET) has been used for decades as a powerful diagnostic technique for diagnosing and tracking tumors in patients. This uncertainty related to a patient’s potential response hampers the effective deployment of this revolutionary class of drugs. Unfortunately, the current assays used to determine PD-L1 expression levels are poorly effective biopsy samples fail to generate a complete picture of heterogeneous tumors, PD-L1 expression is tightly regulated by hormones that are only present in vivo, and the assays themselves are subjectively scored with variable definitions of PD-L1 positivity. However, these drugs will only work if the tumor is expressing the PD-L1 protein. The first therapies to be approved based on the genetic makeup of a tumor instead of the anatomical location and approved for over 15 indications, antibody drugs targeting programmed cell death protein 1 (PD-1) and its ligand (PD-L1) are the premier example of immune checkpoint inhibitors. Immune checkpoint inhibitors have revolutionized the way cancer is treated instead of broadly cytotoxic therapies that “kill the patient, but kill the cancer faster”, these therapeutics enable the immune system’s ability to detect and clear tumors. ![]()
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