Simple synthesis of carbon-11-labeled chromen-4-one derivatives as new potential PET agents for imaging of DNA-dependent protein kinase (DNA-PK) in cancer

Perspective on the Use of DNA Repair Inhibitors as a Tool for Imaging and Radionuclide Therapy of Glioblastoma

“…So far, most DDRi have been directly radiolabeled with 123 I-, 131 I-, 18 F- and 211 At-radionuclides. Only one analog of olaparib was 64 Cu-radiolabeled following conjugation of a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) moiety, allowing for PET imaging of mesothelioma [ 29 , 40 , 49 , 50 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 ].…”

“…It should be noted that the uptake of radiolabeled LY3023414 would not be DNA-PK specific because it also targets PI3K/mTOR. Additionally, the radiosynthesis protocols for 11 C-labelled chromen-4 derivatives as new potential DNA-PK-PET imaging radiopharmaceuticals were published by Gao et al but have not yet been validated in vivo [ 73 ].…”

“… Radiopharmaceuticals targeting DDR kinases studied in various cancer types (for details see Table S2 ). Ataxia-telangiectasia mutated (ATM), ATM-RAD3-related protein (ATR), checkpoint kinase-1 and -2 (CHK1/2), DDR kinase inhibitor (DDRi), DNA-dependent protein kinase (DNA-PK), poly (ADP-ribose) polymerase-1 and -2 (PARP) [ 29 , 40 , 49 , 50 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 ]. …”

Quantitative Structure–Cytotoxicity Relationship of 3-(N-Cyclicamino)chromone Derivatives

“…2-Aminochromone derivatives are reported to have various biological activities including anti-inflammatory activity (6, 7), antimicrobial activity (8), phosphodiesterase inhibition (8,9), modulation of DNA repair (10), inhibition of DNA-dependent protein kinase and radiosensitization of a human tumor cell line (11), and as potential positronemission tomographic agents for imaging of DNA-dependent protein kinase in cancer (12). We recently found that among 15 such 2-(N-cyclicamino)chromone derivatives, 7-methoxy-2-(4-morpholinyl)-4H-1-benzopyran-4-one had the highest tumor specificity, comparable with that of doxorubicin, without induction of apoptosis.…”

Quantitative Structure–Cytotoxicity Relationship of 2-(N-cyclicamino)chromone Derivatives

“…2-Aminochromone derivatives showed various biological activities including anti-inflammatory activity (2,3), antimicrobial activity (3), phosphodiesterase inhibition (4,5), modulation of DNA repair (6), inhibitors of DNA-dependent protein kinase and radiosensitization of a human tumor cell line (7) and new potential PET agents for imaging of DNA-dependent protein kinase (DNA-PK) in cancer (8). On the other hand, the investigation of their anticancer activity, using both human malignant and non-malignant cells, is limited.…”