| 11. |
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| 12. |
- Edwards, David, et al.
(author)
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The in vivo and in vitro metabolic profile of 99mTc-NC100668, a new tracer for imaging venous thromboembolism : identification and biodistribution of the principal radiolabeled metabolite
- 2006
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In: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 34:7, s. 1128-1135
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Journal article (peer-reviewed)abstract
- (99m)Tc-NC100668 [Acetyl-Asn-Gln-Glu-Gln-Val-Ser-Pro-Tyr(3-iodo)-Thr-Leu-Leu-Lys-Gly-NC100194] is a radiopharmaceutical imaging agent being developed to aid the diagnosis of thromboembolism. The stability profile of (99m)Tc-NC100668 was investigated by high-performance liquid chromatography (HPLC) after in vitro exposure to blood and plasma obtained from rat and human, as well as to urine and bile obtained from rat. The metabolic profile of (99m)Tc-NC100668 exposed to human and rat hepatic S9 (a liver homogenate-rich cytochrome P450) was also studied. The profile of (99m)Tc-labeled species in plasma, urine, and bile was investigated following i.v. administration of (99m)Tc-NC100668 to rat. The major species observed in vitro and in vivo consisted of the (99m)Tc-chelator (NC100194) [N,N-Bis(N-(1,1-dimethyl-2-(hydroxylimino-)propyl)aminoethyl)aminoethylamine] attached to the C-terminal amino acid residue and referred to as (99m)Tc-complex of Gly-NC100194. The identity of the major metabolite was confirmed by cochromatography with an authentic standard and the genuine metabolite using a second HPLC method. The minor metabolites were sodium pertechnetate ((99m)Tc) and (99m)Tc-NC100194. In addition, a small number of other species were transiently observed in vitro; they were not investigated further. The biodistribution of the major metabolite was studied in male Wistar rats. The affinity of the major metabolite toward plasma clot was established using a plasma clot-forming assay. A minor uptake of (99m)Tc-complex of Gly-NC100194 in the plasma clot and a rapid removal from the body were noted. In conclusion, the metabolites of (99m)Tc-NC100668 are not anticipated to have a negative impact on the ability of the test substance to image blood clots.
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| 13. |
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| 14. |
- Wang, Anqi, et al.
(author)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Journal article (peer-reviewed)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 15. |
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- 2019
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Journal article (peer-reviewed)
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