Highly Stable ¹⁷⁷Lu-Organic Framework as a Potential Agent for Treatment of Metastatic Bone

Abstract

In this paper, the metal organic framework (MOF) concept is contributed to rearrange the bone-seeking agent composed of carrier-free lutetium-177 (Lu-177), 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraaminomethylenephosphonate (DOTMP) and cupper (II) (Cu (II)) for preparation of a potential agent for treatment of bone metastases. The product was characterized (infra-red spectroscopy, IR, and X-ray diffraction analysis) and quality-controlled (radio-thin layer chromatography, (RTLC)). The stability and in vitro hydroxyapatite binding was checked up to 1.5 month at 37 °C in human serum. Radio-MOF crystals and radio-MOF particles that were obtained by varying the synthesizing conditions (including pH and temperature) showed similar IR patterns and similar elemental analysis results. The final product was synthesized at pH = 8, stirring at room temperature (yield >99%, RTLC, particle size: 90 ± 20 nm). Biodistribution study experiments showed interesting bone-seeking (%ID/g: 8.5%) affinity of the prepared formula with no significant liver or lung uptake. Also high accumulation of radio-complex in bone tissue was estimated by the modeling of the radiation dose delivery using radiation dose assessment resource software. This novel radio-MOF with promising therapeutic results is the first study of the usage of the MOF concept to provide a high payload of Lu-177 for treatment of bone metastases. As it was expected, the most important outcome of the paper was higher bone-uptake rates rather than conventional 177Lu-DOTMP.

Current status and prospects of metal–organic frameworks for bone therapy and bone repair

“…Researchers rearranged a bone-seeking agent consisting of carrier-free 177 Lu, 1,4,7,10-tetraazacyclododecane–1,4,7,10-tetraaminomethylphosphonate (DOTMP) and copper( ii ) to prepare a potential bone metastasis therapeutic drug, 177 Lu–DOTMP–Cu, using a combination of radionuclide, bone-seeking agent and MOF concepts. 44 Two important advantages of using the MOF concept in combination with radionuclides are the use of a small amount of material that can provide high flux of metal ions and the prevention of the release of free radionuclides from the compound. The final 177 Lu–DOTMP–Cu was synthesized at room temperature at pH 8 under stirring (yield > 99%, RTLC, particle size: 90 ± 20 nm).…”

A bone-targeting drug delivery vehicle of a metal–organic framework conjugate with zoledronate combined with photothermal therapy for tumor inhibition in cancer bone metastasis

“…MOFs are easily functionalized, and their structure, pore size, and dimensions can be adjusted. [15][16][17][18][19] MOF nanoparticles (nMOFs) are outstanding carriers for absorbing organic small molecules for the sustained release of pharmaceutical molecules. 20,21 Wang et al constructed a MOF that was connected to TBD after encapsulating Pt(IV) within polyethylene glycol, which showed enhanced chemotherapeutic efficacy and fewer side effects.…”