[18F]AlF-cysVar3 pHLIP

[18F]AlF-cysVar3 pHLIP is a first-in-class PET (Positron Emission Tomography) imaging radiopharmaceutical designed to target the acidic extracellular microenvironment characteristic of solid tumors and other pathological conditions. It is based on the **pH (Low) Insertion Peptide (pHLIP)** technology, which utilizes water-soluble peptides that remain unstructured at physiological pH (7.4) but undergo a conformational change into an alpha-helix that inserts unidirectionally into cell membranes when the extracellular pH drops below 7.0. The specific **cysVar3** variant (Variant 3 modified with a cysteine residue) is conjugated to a Fluorine-18 labeled aluminum fluoride ([18F]AlF) complex via a chelator such as **NO2A**. This mechanism allows for high-contrast imaging of metabolic acidity—a hallmark of aggressive, glycolytic, and hypoxic tumors—independent of glucose uptake (FDG). Primarily developed through a collaboration between **Memorial Sloan Kettering Cancer Center** and **pHLIP**, the agent is currently in Phase 1 clinical trials for the evaluation of breast cancer and is being investigated for its ability to assess tumor aggressiveness and therapeutic response.

Other names

18F-AlF-pHLIP-Var3[18F]AlF-cysVar3 pHLIP®Aluminum [18F]fluoride-cysVar3 pHLIP