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The ability of bacteria to recycle exogenous amino acid-based peptides and amino sugars for peptidoglycan biosynthesis was extensively investigated using optical imaging. In particular, fluorescent AeK–NBD was effectively utilized to study the peptidoglycan recycling pathway in Gram-negative bacteria. Based on these promising results, we were inspired to develop the radioactive AeK conjugate [68Ga]Ga-DOTA-AeK for the in vivo localization of bacterial infection using PET/CT. An easy-to-implement radiolabeling procedure for DOTA-AeK with [68Ga]GaCI3 followed by solid-phase purification was successfully established to obtain [68Ga]Ga-DOTA-AeK with a radiochemical purity of ≥95%. [68Ga]Ga-DOTA-AeK showed good stability over time with less protein binding under physiological conditions. The bacterial incorporation of [68Ga]Ga-DOTA-AeK and its fluorescent Aek-NBD analog were investigated in live and heat-killed Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Unfortunately, no conclusive in vitro intracellular uptake of [68Ga]Ga-DOTA-AeK was observed for E. coli or S. aureus live and heat-killed bacterial strains (p > 0.05). In contrast, AeK-NBD showed significantly higher intracellular incorporation in live bacteria compared to the heat-killed control (p < 0.05). Preliminary biodistribution studies of [68Ga]Ga-DOTA-AeK in a dual-model of chronic infection and inflammation revealed limited localization at the infection site with non-specific accumulation in response to inflammatory markers. Finally, our study demonstrates proof that the intracellular incorporation of AeK is necessary for successful bacteria-specific imaging using PET/CT. Therefore, Ga-68 was not a suitable radioisotope for tracing the bacterial uptake of AeK tripeptide, as it required chelation with a bulky metal chelator such as DOTA, which may have limited its active membrane transportation. An alternative for optimization is to explore diverse chemical structures of AeK that would allow for radiolabeling with 18F or 11C. [ABSTRACT FROM AUTHOR]

The actinium-225 (225Ac) radioisotope exhibits highly attractive nuclear properties for application in radionuclide therapy. However, the 225Ac radionuclide presents multiple daughter nuclides in its decay chain, which can escape the targeted site, circulate in plasma, and cause toxicity in areas such as kidneys and renal tissues. Several ameliorative strategies have been devised to circumvent this issue, including nano-delivery. Alpha-emitting radionuclides and nanotechnology applications in nuclear medicine have culminated in major advancements that offer promising therapeutic possibilities for treating several cancers. Accordingly, the importance of nanomaterials in retaining the 225Ac daughters from recoiling into unintended organs has been established. This review expounds on the advancements of targeted radionuclide therapy (TRT) as an alternative anticancer treatment. It discusses the recent developments in the preclinical and clinical investigations on 225Ac as a prospective anticancer agent. Moreover, the rationale for using nanomaterials in improving the therapeutic efficacy of α-particles in targeted alpha therapy (TAT) with an emphasis on 225Ac is discussed. Quality control measures in the preparation of 225Ac-conjugates are also highlighted. [ABSTRACT FROM AUTHOR]