Tc-Labeled citric acid-folate conjugate, abbreviated as Tc-citro-folate, was synthesized by Altiparmak et al. for folate receptor (FR)-targeted imaging of FR-positive tumors (1). Folate (folic acid) is an essential vitamin for cell synthesis of nucleotide bases. Some unique features of the FR-folate system make it a valuable target for developing FR-targeted imaging and therapeutic agents (2-4). First, FR has a high affinity for the exogenous folate conjugates ( = ~100 pM), but the reduced folate carrier and the proton coupled folate transporters display very low or no affinity for folate conjugates. Second, the FR-α isoform is overexpressed in ~40% of human cancer tissues, where it is completely accessible to folate conjugates, but the FR-α is inaccessible for the conjugates in most normal tissues because its expression occurs largely at the apical (luminal) surface of epithelial cells where it is not supplied with blood vessels . Third, folate conjugates are taken up by cancer cells FR-mediated endocytosis, and FR recycles actively to the cell surface with a frequency of 5.7–20 h, depending on cell types. Fourth, conjugation of imaging labels the γ-carboxyl group of folate has no apparent effects on the ligand-binding affinity to FR. Furthermore, folate is a small molecule (MW = ~441) and exhibits rapid and complete penetration of solid tumors and rapid clearance from FR-negative tissues (, <10 min). One disadvantage of the FR-folate system is that FR expresses at a relatively low density on the tumor cell surface (1–3 million FR/cell), and binding saturation can be reached rapidly; these characteristics can limit the FR-targeted imaging contrast (5, 6). Therefore, sensitive imaging techniques such as positron emission tomography and single-photon emission computed tomography (SPECT) appear to be more suitable for FR-targeted imaging (2, 3, 7). To date, a large set of folate-based radiopharmaceutical agents have been synthesized for nuclear imaging. In general, a chelating agent is necessary for bridging the radiolabels and the folate molecule; a chelating agent is also critical for optimizing the pharmacokinetics of the compound (1, 8). Altiparmak et al. synthesized Tc-citro-folate using citric acid as a chelating agent (1). Biodistribution studies showed accumulation of the compound in FR-rich tissues and demonstrated its potential for clinical imaging of FR-positive tumors. Tc is widely used for nuclear imaging because of its ideal energy (Eγ = 140 keV), low radiation dose, long half-life (, 6 h), and commercial availability (1).