Angiogenesis is a fundamental feature of tumor development, and therefore, the tracers for molecular imaging of specific angiogenic biomarkers are expected to be useful for diagnostics, patient monitoring, and drug development. We have created a new class of imaging agents based on the most important mediator of angiogenesis, vascular endothelial growth factor (VEGF). Our latest version is a single-chain (sc) VEGF protein containing an N-terminal Cys-tag designed for site-specific modification with a variety of imaging and therapeutic moieties. We have recently found that the Cys-tag itself can form a stable chelate with (99m)Tc using tin-tricine as an exchange reagent. This self-chelation approach yields a highly stable and fully functional form of radiolabeled scVEGF that can be used as a SPECT tracer for tumor angiogenesis. Also of note is that directly labeled scVEGF has less than one-half the nonspecific renal uptake of (99m)Tc-HYNIC-scVEGF. The simple production of scVEGF for direct chelation of (99m)Tc makes it a promising molecular imaging agent for the oncology clinic.