PurposeIn this study, DOTA-IBA was radiolabeled with 68Ga and we determined the optimum labelling conditions and assessed the biological properties of 68Ga-DOTA-IBA. We investigated the biodistribution of 68Ga-DOTA-IBA in normal animals and undertook PET/CT imaging in humans. Finally, we explored the feasibility 68Ga-DOTA-IBA as a bone imaging agent and demonstrated its potential for the therapeutic release of 177Lu/225Ac-DOTA-IBA.MethodsThe controlled variables method was used to assess the impact of variables on the radiochemical purity of 68Ga-DOTA-IBA. The biological properties of 68Ga-DOTA-IBA were investigated.68Ga-DOTA-IBA micro-PET/CT imaging was performed on animals. Volunteers were recruited for 68Ga-DOTA-IBA imaging and data were compared to 99mTc-MDP imaging studies to calculate the target to non-target ratio (T/NT) of the lesions.ResultsThe prepared 68Ga-DOTA-IBA had a radiochemical purity of >97% and demonstrated good biological properties with a good safety profile in normal mice. PET/CT imaging of the animals showed rapid blood clearance with high contrast between the bone and stroma. Human imaging showed that 68Ga-DOTA-IBA could detect more lesions compared to 99mTc-MDP and had a higher targeted to untargeted ratio.Conclusions68Ga-DOTA-IBA is an osteophilic radiopharmaceutical that can be synthesized using a simple labelling method. 68Ga-DOTA-IBA has high radiochemical purity and is stable in vitro stability. It is rapidly cleared from the blood, has low toxicity and has strong targeting to the bone with long retention times. We also found that it is rapidly cleared in non-target tissues and has high contrast on whole-body bone imaging. 68Ga-DOTA-IBA PET/CT has potential as a novel bone imaging bone modality in patients with metastatic disease.

A one-pot synthesis, initiated by a copper salt with (NH4)2CO3 as the nitrogen source, forms divergent aryl imidazole derivatives from ketones via C–H activation, α-amination and oxidative C–C bond cleavage and condensation cascade reaction.

Many sulfonamides show anticancer activity. Based on benzenesulfonylazaspirodienone (HL-X9) identified in our previous work, we optimized the lead compound for better efficacy, thereby synthesizing a series of novel 4-(aromatic sulfonyl)-1-oxa-4-azaspiro[4.5]deca-6,9-dien-8-one derivatives through a key step of metal-catalyzed cascade cyclization. The preliminary antiproliferative tests have shown that the anticancer activities of acetyl-protected mannose-linked sulfonylazaspirodienone derivatives (7i–7l) have been greatly improved. Among them, 7j is the most potent derivative, with IC50 values of 0.17 µM, 0.05 µM, and 0.07 µM for A549, MDA-MB-231, and HeLa cell lines, respectively. Flow cytometry analysis shows that 7j arrests MDA-MB-231 cells in the G2/M phase and has a certain effect on the apoptosis of MDA-MB-231 cells. In addition, the acute toxicity of 7j was lower than that of adriamycin.

A new copper-catalyzed one-pot reaction resulted in the practical synthesis of imidazolinones from esters.

Among different FAPIs (fibroblast activation protein inhibitors) developed for PET imaging, 68Ga-FAPI-04 has demonstrated the most impressive properties with low nanomolar affinity to FAP, near-complete internalization of radioactivity bound to FAP, and rapid blood clearance. The application of 68Ga-FAPI-04 has been extended to 28 different kinds of clinical cancer detection. The manual synthesis of 68Ga-FAPI-04 is like other 68Ga-labeling peptides, such as PSMA-11 and DOTATATE. However, because the radiochemical conversion (RCC) is about 90%, it is required to conduct a purification and isolation process to meet the required standard for clinical application. The purpose of this work is to characterize the increase of isolation efficiency (IE) by increasing the volume of eluting liquid applied to C18 columns and sterile filters. We designed an experiment and measured the residual activity distribution on both C18 columns and sterile filters for different eluting volumes. We characterized the change of activity residuals and isolation efficiencies with different eluting volumes in the process of purification and isolation. As a result, it was found that there were more activity leftovers on sterile filters than on C18 columns. By increasing the eluting volume from 6 mL to 12 mL, we measured the average IE being improved from 62.4% to 87.4%, which is greatly beneficial to clinical applications. In addition, the fluctuation of IE which might come from the different radiolabeling operators or materials used in the experiment, was also obviously decreased from 11.3% to 4.5%. This method has been proven to be efficient in the production of 68Ga-FAPI-04.