Uses a ratcheting action to create tension in the chain. The method of tightening the binder is what differentiates the two. There are two general styles of chain binders ratchet binder and lever binder. The addition of albumin binder motifs to Lu-DOTATATE enhanced mean residence time in blood. What is a chain binder Also called a load binder, chain binders are a device to tighten chain when securing a load for transport. Renal uptake was 7.49 В± 1.62%ID/g for Lu-DOTATATE, 31.14 В± 7.06%ID/g for Lu-GluAB-DOTATATE, and 28.82 В± 13.82%ID/g for Lu-AspAB-DOTATATE at 1 h and decreased thereafter. For Lu-GluAB-DOTATATE tumour uptake increased from 21.89 В± 6.86%ID/g at 1 h to 24.44 В± 5.84%ID/g at 4 h, before decreasing to 12.02 В± 1.84%ID/g at 120 h. Tumour uptake of Lu-DOTATATE was 21.35 В± 5.90%ID/g at 1 h and decreased to 10.10 В± 5.78%ID/g at 120 h. In vivo, Lu-GluAB-DOTATATE and Lu-AspAB-DOTATATE had significantly higher blood activity at 1, 4 and 24 h compared to Lu-DOTATATE. The 177Lu-labeled peptides were obtained in non-decay-corrected isolated yields of в‰Ґ41%, with >96% radiochemical purity, and molar activities in the range of 314-497 GBq/Ојmol. 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.ДOTATATE 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.

Binder chain