This preliminary investigation of the octadentate acyclic chelator H(4)octapa (N4O4) with In-111/In-115(3+) has demonstrated it to be an improvement on the shortcomings of the current industry "gold standards" DOTA (N4O4) and DTPA (N3O5). The ability of H(4)octapa to radiolabel quantitatively (InCl3)-In-111 at ambient temperature in 10 min with specific activities as high as 2.3 mCi/nmol (97.5% radiochemical yield) is presented. In vitro mouse serum stability assays have demonstrated the In-111 complex of H(4)octapa to have improved stability when compared to DOTA and DTPA over 24 h. Mouse biodistribution studies have shown that the radiometal complex [In-111(octapa)](-) has exceptionally high in vivo stability over 24 h with improved clearance and stability compared to [In-111(DOTA)](-), demonstrated by lower uptake in the kidneys, liver, and spleen at 24 h. H-1/C-13 NMR studies of the [In(octapa)](-) complex revealed a 7-coordinate solution structure, which forms a single isomer and exhibits no observable fluxional behavior at ambient temperature, an improvement to the multiple isomers formed by [In(DTPA)](2-) and [In(DOTA)](-) under the same conditions. Potentiometric titrations have determined the thermodynamic formation constant of the [In(octapa)](-) complex to be log K-ML = 26.8(1). Through the same set of analyses, the [In-111/115(decapa)](2-) complex was found to have nonoptimal stability, with H(5)decapa (N5O5) being more suitable for larger metal ions due to its higher potential denticity (e.g., lanthanides and actinides). Our initial investigations have revealed the acyclic chelator H(4)octapa to be a valuable alternative to the macrocycle DOTA for use with In-111, and a significant improvement to the acyclic chelator DTPA.