CAIX-targeted PET/CT in Solid Tumors

Overview

Tumor hypoxic microenvironment plays an important role in the initiation and progression of solid tumors, as well as tumor invasion, metastasis, and treatment resistance. Carbonic anhydrase IX (CAIX), as a crucial downstream molecule regulated by hypoxia-inducible factor-1 (HIF-1), is highly expressed in various solid tumors and is closely associated with tumor invasiveness, treatment response, and prognosis; thus, it represents an ideal target for tumor diagnosis and therapy. This study aims to explore the diagnostic value of CAIX-targeted PET/CT imaging in various solid tumors, as well as the correlation between tumor uptake and tissue CAIX expression.

A hallmark of solid tumors is their intrinsic hypoxic microenvironment, which is not only closely associated with tumor metabolic reprogramming, angiogenesis, invasion, and metastasis, but also represents a key factor contributing to resistance to radiotherapy, chemotherapy, as well as certain targeted and immunotherapeutic approaches. Therefore, achieving precise, non-invasive imaging of tumor hypoxia has become a cutting-edge and prominent focus in current cancer research. Among hypoxia-related molecules, carbonic anhydrase IX (CAIX) is the most representative target for research. As a key downstream target gene of the hypoxia-inducible factor-1 (HIF-1) pathway, CAIX expression levels are closely correlated with the hypoxic state and play an important role in regulating extracellular acidification in tumor cells as well as maintaining intracellular acid-base homeostasis; CAIX is intimately involved in the survival, proliferation, invasion, and metastasis of cancer cells. Studies have demonstrated that high CAIX expression is often associated with greater tumor invasiveness, an increased risk of metastasis, and a worse patient prognosis. Compared to other hypoxia-related molecules, CAIX expression is relatively limited in normal tissues-primarily observed in a small number of tissues such as certain gastrointestinal epithelial cells-but it exhibits abnormally high expression in various malignant tumors, including clear cell renal cell carcinoma, non-small cell lung cancer, colorectal cancer, breast cancer, and brain tumors. Therefore, CAIX is considered a highly promising diagnostic and therapeutic target for solid tumors. CAIX-targeted molecular imaging probes can be classified into three major categories based on their molecular structure: antibody-based probes, small molecule-based probes, and peptide-based probes. Several CAIX-targeted probes (e.g., 68Ga-DPI-4452, 68Ga-NY104, and 18F-AlF-NYM005) have currently entered the clinical translation phase and demonstrated promising diagnostic potential for the detection of clear cell renal cell carcinoma; however, their clinical value in the diagnosis of other solid tumors remains unclear. Therefore, this study aims to further evaluate the diagnostic value of CAIX-targeted PET/CT imaging in various solid tumors (including renal cell carcinoma, non-small cell lung cancer, colorectal cancer, breast cancer, etc.) and to explore the correlation between tumor uptake and tissue CAIX expression, thereby providing a scientific basis for its subsequent routine clinical application.