The addition of albumin binder motifs to Lu-DOTATATE enhanced mean residence time in blood. Renal uptake was 7.49 ± 1.62%ID/g for Lu-DOTATATE, 31.14 ± 7.06%ID/g for Lu-GluAB-DOTATATE, and 28.82 ± 13.82%ID/g for Lu-AspAB-DOTATATE at 1 h and decreased thereafter. For Lu-GluAB-DOTATATE tumour uptake increased from 21.89 ± 6.86%ID/g at 1 h to 24.44 ± 5.84%ID/g at 4 h, before decreasing to 12.02 ± 1.84%ID/g at 120 h. Tumour uptake of Lu-DOTATATE was 21.35 ± 5.90%ID/g at 1 h and decreased to 10.10 ± 5.78%ID/g at 120 h. A ratchet binder uses a ratcheting mechanism to tension the chain, while a lever binder uses leverage to tighten and secure the load.
We carry two styles of binders, ratchet-style and lever-style. In vivo, Lu-GluAB-DOTATATE and Lu-AspAB-DOTATATE had significantly higher blood activity at 1, 4 and 24 h compared to Lu-DOTATATE. Also known as load binders, chain binders are essential tie down equipment in the flatbed industry. The 177Lu-labeled peptides were obtained in non-decay-corrected isolated yields of ≥41%, with >96% radiochemical purity, and molar activities in the range of 314-497 GBq/μmol. The compounds exhibited nanomolar binding affinity (K i: 8.72-8.95 nM) for SSTR2. GluAB-DOTATATE and AspAB-DOTATATE were synthesized in 18.8% and 14.3% yields, while Lu-GluAB-DOTATATE and Lu-AspAB-DOTATATE were obtained in 86.5% and 50.0% yields, respectively. SPECT imaging and biodistribution studies (1, 4, 24, 72, and 120 h) were performed in immunodeficient mice bearing AR42J pancreatic tumour xenografts.
Compounds were radiolabeled with LuCl 3 and purified by HPLC. Binding affinities of the Lu-labeled peptides for human somatostatin receptor 2 (SSTR2) were measured with membrane competition binding assays. We investigated whether prolonging blood residence time of Lu-DOTATATE with albumin binders could increase tumour accumulation and tumour-to-kidney ratios for improved therapeutic efficacy.ĭOTATATE and its derivatives with an albumin-binder motif (GluAB-DOTATATE and AspAB-DOTATATE) were prepared by solid-phase peptide synthesis. Lu-DOTATATE peptide receptor radionuclide therapy is used for treatment of neuroendocrine tumours.
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