In a search for an infarct avid tracer agent with improved properties, we have observed that bis-DTPA derivatives of pamoic acid have a high avidity for necrotic tissue. Here, we report the synthesis, radiolabeling, and preliminary evaluation in normal mice and rats with hepatic infarction of the Tc-99m-tricarbonyl complexes of N,N'-bis(diethylenetriamino-pentaacetato)-4,4'-methylene bis(2-hydroxy-3-naphthoic hydrazide) (Tc-99m(CO)(3)-bis-DTPA-pamoate) and [N-(5-aminopentyl)pyridin-2-yl-methylamino] methylacetato-4,4'-methylene-2-hydroxy-3-napthalenecarboxamide-(2'-hydroxy-3'-naphthoic acid methyl ester) (Tc-99m(CO)(3)-12). Radiolabeling with Tc-99m(CO)(3)(+) was achieved with a radiochemical yield of over 95% for both tracer agents. In normal mice, the polar Tc-99m(CO)(3)-bis-DTPA-pamoate was cleared from plasma via both the liver and the kidneys, while the more lipophilic Tc-99m(CO)(3)-12 was rapidly cleared via the liver. Blood clearance in mice was faster for Tc-99m(CO)(3)-12(0.1% injected dose per gram at 4 h postinjection) than for C-99m(CO)(3)-bis-DTPA-pamoate (9.3% injected dose per gram at 4 h postinjection). Affinity and specificity of the tracers for necrotic tissue was studied in rats with hepatic infarction and ethanol-induced necrosis of the liver or muscles. Activity ratios of infarct to viable liver tissue of Tc-99m(CO)(3)-bis-DTPA-pamoate quantified by autoradiography of tissue slices ranged from 4 to 18, depending on the necrosis model and time postinjection of the tracer. Infarcts were also visualized in vivo by Tc-99m(CO)(3)-bis-DTPA-pamoate planar gamma imaging. After injection of Tc-99m(CO)(3)-bisDTPA-pamoate, in vivo and ex vivo images correlated well with histochemical staining with triphenyltetrazolium chloride and hematoxylin and eosin. Tc-99m(CO)(3)-12 on the other hand showed no uptake in necrotic tissue. Stability of the tracers was determined in vitro after storage at room temperature and by histidine challenge experiments, and in vivo in mouse plasma and in urine (for Tc-99m(CO)3-bis-DTPA-pamoate). Tc-99m(CO)(3)-bis-DTPA-pamoate was unstable in vitro to histidine challenge, while 99mTc(CO)3-12 was 98% stable in vitro in the same conditions. Both tracers showed good in vivo stability. Tc-99m(CO)(3)-bis-DTPA-pamoate shows high specificity for necrotic tissue and merits further evaluation as a necrosis avid imaging agent. Tc-99m(CO)(3)-12 is not useful for visualization of necrotic tissue.