LUTETIUM-177 LABELED ZEOLITIC IMIDAZOLATE FRAMEWORKS FOR BIOMEDICAL APPLICATIONS

Zeolitic imidazolate frameworks (ZIF-8) are promising radionuclide carriers due to their high stability and surface functionalization potential. In this study, ZIF-8 was synthesized using a two-step process. First, (Zn,Zn) hydroxy double salt (HDS) was prepared by mixing an aqueous ZnO suspension (1 M), Zn(CH₃CO₂)₂ aqueous solution (1 M), and DMF for 24 hours. The (Zn,Zn) HDS suspension was then added to a 2-methylimidazole (6 mmol) DMF solution under rapid magnetic stirring at room temperature for 10 minutes. The obtained product was filtered and air-dried [1]. The efficiency of ZIF-8 radiolabeling with lutetium-177 (¹⁷⁷Lu) was investigated under various experimental conditions. The results showed that the obtained samples exhibited a high radiolabeling yield (>94%), with the highest value of 98.8% recorded for samples treated at 70°C. In vitro testing under physiological conditions confirmed the high stability of the radiolabeled samples, with less than 9.2% of ¹⁷⁷Lu³⁺ released after 14 days of incubation in human serum. Theoretical analyses based on density functional theory (DFT) calculations identified key interactions responsible for the stable incorporation of ¹⁷⁷Lu within the ZIF-8 structure. Electrostatic potential mapping revealed regions with a high affinity for ¹⁷⁷Lu³⁺ adsorption, with primary binding mechanisms involving coordination with Zn-OH groups and N-H groups of imidazole. FTIR analysis confirmed the formation of coordination bonds between lutetium and ZIF-8 functional groups, with spectroscopic shifts indicating Zn-O-Lu and Lu-N interactions. The obtained results in this study and literature data [2] highlight the potential of ZIF-8 for the simultaneous integration of therapeutic (¹⁷⁷Lu) and diagnostic (⁹⁹ᵐTc) radionuclides, enabling its application in tumor theranostics. Additionally, radiolabeled ZIF-8 exhibits characteristics compatible with other metal-organic frameworks (MOFs), further confirming its versatility as a platform for radionuclide therapy.