In order to seek novel technetium-99m bacterial infection imaging agents, a ciprofloxacin xanthate (CPF2XT) was synthesized and radiolabeled with [^99mTcN]²⁺ core to obtain the ^99mTcN-CPF2XT complex, which exhibited high radiochemical purity, hydrophilicity, and good stability in vitro. The bacteria binding assay indicated that ^99mTcN-CPF2XT had specificity to bacteria. A study of biodistribution in mice showed that ^99mTcN-CPF2XT had a higher uptake in bacterial infection tissues than in turpentine-induced abscesses, indicating that it could distinguish bacterial infection from sterile inflammation. Compared to ^99mTcN-CPFXDTC, the abscess/blood and abscess/muscle ratios of ^99mTcN-CPF2XT were higher and the uptakes of ^99mTcN-CPF2XT in the liver and lung were obviously decreased. The results suggested that ^99mTcN-CPF2XT would be a potential bacterial infection imaging agent.

To develop novel ^99mTc-labeled single-photon emission computed tomography (SPECT) radiotracers for imaging hypoxia, a novel HYNICNM ligand (6-hydrazinonicotinamide (HYNIC) 2-nitroimidazole derivative) was designed and synthesized. It was radiolabeled with technetium-99m using tricine/trisodium triphenylphosphine-3,3′,3′′-trisulfonate (TPPTS), tricine/sodium triphenylphosphine-3-monosulfonate (TPPMS) and tricine as co-ligands to obtain [^99mTc]Tc-tricine-TPPTS-HYNICNM, [^99mTc]Tc-tricine-TPPMS-HYNICNM, and [^99mTc]Tc-(tricine)₂-HYNICNM, respectively. The three technetium-99m complexes were radiolabeled in one step with a high yield (95%) and had good stability in saline and mouse serum. In vitro cellular uptake results showed that these complexes exhibited good hypoxic selectivity. The partition coefficient indicated that they were good hydrophilic complexes, and [^99mTc]Tc-tricine-TPPTS-HYNICNM displayed the highest hydrophilicity (−3.02 ± 0.08). The biodistribution in mice bearing S180 tumors showed that [^99mTc]Tc-tricine-TPPTS-HYNICNM exhibited higher tumor uptake (1.05 ± 0.27% IA/g); more rapid clearance from the liver, blood, muscle, and other non-target organs; and a higher tumor/non-target ratio, especially for the tumor/liver ratio (1.95), than [^99mTc]Tc-tricine-TPPMS-HYNICNM and [^99mTc]Tc-(tricine)₂-HYNICNM. The results of single-photon emission computed tomography (SPECT) imaging studies of [^99mTc]Tc-tricine-TPPTS-HYNICNM were in accordance with the biodistribution results, which suggested that [^99mTc]Tc-tricine-TPPTS-HYNICNM is a promising agent for imaging tumor hypoxia.

To develop potential technetium-99m single-photon emission computed tomography (SPECT) imaging agents for bacterial infection imaging, the novel norfloxacin isonitrile derivatives CN4NF and CN5NF were synthesized and radiolabeled with a [^99mTc][Tc(I)]⁺ core to obtain [^99mTc]Tc-CN4NF and [^99mTc]Tc-CN5NF. These compounds were produced in high radiolabeling yields and showed hydrophilicity and good stability in vitro. The bacterial binding assay indicated that [^99mTc]Tc-CN4NF and [^99mTc]Tc-CN5NF were specific to bacteria. Compared with [^99mTc]Tc-CN4NF, biodistribution studies of [^99mTc]Tc-CN5NF showed a higher uptake in bacteria-infected tissues than in turpentine-induced abscesses, indicating that [^99mTc]Tc-CN5NF could distinguish bacterial infection from sterile inflammation. In addition, [^99mTc]Tc-CN5NF had higher abscess/blood and abscess/muscle ratios. SPECT image of [^99mTc]Tc-CN5NF showed that there was a clear accumulation in the infection site, suggesting that it could be a potential bacterial infection imaging radiotracer.