Definition

A radioconjugate composed of pH (low) insertion peptides (pHLIP) variant 3 (Var3) conjugated, via a cysteine residue, to fluorine F 18-labeled aluminum fluoride (AlF) complex, with potential use as an imaging agent for the acidic extracellular environment surrounding tumors upon positron emission tomography (PET). Upon administration of fluorine F 18-AlF-cys-Var3 pHLIP, the Var3 pHLIP moiety specifically targets, tightly binds to and gets inserted into the cellular membrane of tumor cells in environments with low extracellular pH. Upon PET, tumor cells and the extent of acidity can be visualized and assessed using PET. Tumor cell environments are more acidic than normal, healthy tissue environments. The pHLIPs specifically fold into an alpha-helical conformation and become inserted across the membrane at low extracellular pH whereas they are unfolded and unbound at higher pHs.