FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2030796695> ?p ?o ?g. }

• W2030796695 endingPage "437" @default.
• W2030796695 startingPage "429" @default.
• W2030796695 abstract "Sugar conjugation of biooactive peptides has been shown to be a powerful tool to modulate peptide pharmacokinetics. In the case of radiolabeled somatostatin analogues developed for in vivo scintigraphy of somatostatin receptor (sst) expressing tumors, it generally led to tracers with predominant renal excretion and low uptake in nontarget organs, and in some cases also with enhanced tumor accumulation. Especially with respect to endoradiotherapeutic applicability of these tracers, however, understanding the structural requirements for minimal kidney accumulation and maximal tumor uptake is important. The aim of this study was therefore the evaluation of the potential of specific glycoside structures in combination with reduced peptide net charge to reduce kidney accumulation without affecting tumor accumulation. Three glyco analogues of radioiodinated Tyr(3)-octreotate (TOCA) with z = 0 were evaluated in a comparative study using [(125)I]Mtr-TOCA (z = +1), the maltotriose-Amadori analogue of [(125)I]TOCA, as a reference, [(125)I]Glucuron-TOCA, the Amadori conjugate with glucuronic acid, and [(125)I]Gluc-S- and [(125)I]Gal-S-TOCA, the coupling products with glucosyl- and mannosyl-mercaptopropionate. In cells transfected with sst(1)-sst(5), all three new analogues show sst-subtype binding profiles similar to I-Mtr-TOCA with high, but somewhat reduced, affinity for sst(2). In contrast, internalization into sst(2)-expressing cells (in % of [(125)I]Tyr(3)-octreotide ([(125)I]TOC)) as well as the EC(50,R) of unlabeled TOC for internalization determined in dual-tracer experiments are substantially enhanced for [(123)I]Gal-S-TOCA and [(123)I]Gluc-S-TOCA (internalization, 190% +/- 12% and 265% +/- 20%, respectively, vs 168% +/- 6% of [(125)I]TOC for [(123)I]Mtr-TOCA; EC(50,R), 2.62 +/- 0.07 and 2.96 +/- 0.14, respectively, vs 1.81 +/- 0.07 for [(123)I]Mtr-TOCA). The tumor accumulation of [(125)I]Gal-S-TOCA and [(125)I]Gluc-S-TOCA in AR42J tumor-bearing nude mice 1 h p.i. is consequently very high (22.6 +/- 2.2 and 26.2 +/- 5.6%ID/g) and comparable to that of [(125)I]Mtr-TOCA (25.1 +/- 4.4%ID/g). [(125)I]Glucuron-TOCA showed lower uptake in sst-expressing tissues than did [(125)I]Mtr-TOCA, but considerably enhanced accumulation in nontarget organs such as liver, intestine, and kidney. Due to increased lipophilicity, hepatic and intestinal uptake 1 and 4 h p.i. of [(125)I]Gal-S-TOCA and [(125)I]Gluc-S-TOCA was also slightly higher than that of [(125)I]Mtr-TOCA. Kidney accumulation, however, was reduced by approximately 50% for both compounds (2.6 +/- 0.3 and 2.2 +/- 0.4, respectively, vs 4.0 +/- 0.7%ID/g at 1 h p.i.). Because no sugar-specific effect was detected in the latter case, it is concluded that general ligand pharmacokinetics and especially kidney accumulation of the tracers investigated are mainly determined by physicochemical characteristics such as lipophilicity, net charge, and also charge distribution ([(125)I]Glucuron-TOCA vs [(125)I]Gal-S- and [(125)I]Gluc-S-TOCA). With respect to receptor targeting, however, the structure of the carbohydrate moiety plays an important role, leading to dramatically enhanced ligand internalization, especially in the case of [(123)I]Gluc-S-TOCA. Taking into account the combined effects of the Gluc-S-moiety both on kidney and on tumor accumulation, this group seems to be a promising synthon for the synthesis of other radiolabeled peptide analogues with improved pharmacokinetics." @default.
• W2030796695 created "2016-06-24" @default.
• W2030796695 creator A5000481071 @default.
• W2030796695 creator A5022226042 @default.
• W2030796695 creator A5046506925 @default.
• W2030796695 creator A5051959238 @default.
• W2030796695 creator A5055684567 @default.
• W2030796695 date "2005-02-22" @default.
• W2030796695 modified "2023-09-27" @default.
• W2030796695 title "Modulation of Pharmacokinetics of Radioiodinated Sugar-Conjugated Somatostatin Analogues by Variation of Peptide Net Charge and Carbohydration Chemistry" @default.
• W2030796695 cites W1974375072 @default.
• W2030796695 cites W1994083019 @default.
• W2030796695 cites W1999429628 @default.
• W2030796695 cites W2005674134 @default.
• W2030796695 cites W2044357064 @default.
• W2030796695 cites W2050129233 @default.
• W2030796695 cites W2056584927 @default.
• W2030796695 cites W2063446597 @default.
• W2030796695 cites W2081762302 @default.
• W2030796695 cites W2083336327 @default.
• W2030796695 cites W2088798345 @default.
• W2030796695 cites W2175128997 @default.
• W2030796695 doi "https://doi.org/10.1021/bc0499228" @default.
• W2030796695 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15769098" @default.
• W2030796695 hasPublicationYear "2005" @default.
• W2030796695 type Work @default.
• W2030796695 sameAs 2030796695 @default.
• W2030796695 citedByCount "37" @default.
• W2030796695 countsByYear W20307966952012 @default.
• W2030796695 countsByYear W20307966952013 @default.
• W2030796695 countsByYear W20307966952014 @default.
• W2030796695 countsByYear W20307966952015 @default.
• W2030796695 countsByYear W20307966952016 @default.
• W2030796695 countsByYear W20307966952017 @default.
• W2030796695 countsByYear W20307966952018 @default.
• W2030796695 countsByYear W20307966952019 @default.
• W2030796695 countsByYear W20307966952021 @default.
• W2030796695 countsByYear W20307966952022 @default.
• W2030796695 countsByYear W20307966952023 @default.
• W2030796695 crossrefType "journal-article" @default.
• W2030796695 hasAuthorship W2030796695A5000481071 @default.
• W2030796695 hasAuthorship W2030796695A5022226042 @default.
• W2030796695 hasAuthorship W2030796695A5046506925 @default.
• W2030796695 hasAuthorship W2030796695A5051959238 @default.
• W2030796695 hasAuthorship W2030796695A5055684567 @default.
• W2030796695 hasConcept C100817775 @default.
• W2030796695 hasConcept C112705442 @default.
• W2030796695 hasConcept C134018914 @default.
• W2030796695 hasConcept C134306372 @default.
• W2030796695 hasConcept C139770010 @default.
• W2030796695 hasConcept C150903083 @default.
• W2030796695 hasConcept C170493617 @default.
• W2030796695 hasConcept C185592680 @default.
• W2030796695 hasConcept C197336794 @default.
• W2030796695 hasConcept C207001950 @default.
• W2030796695 hasConcept C2776297358 @default.
• W2030796695 hasConcept C2776648616 @default.
• W2030796695 hasConcept C2779281246 @default.
• W2030796695 hasConcept C33923547 @default.
• W2030796695 hasConcept C55493867 @default.
• W2030796695 hasConcept C71924100 @default.
• W2030796695 hasConcept C86803240 @default.
• W2030796695 hasConcept C98274493 @default.
• W2030796695 hasConceptScore W2030796695C100817775 @default.
• W2030796695 hasConceptScore W2030796695C112705442 @default.
• W2030796695 hasConceptScore W2030796695C134018914 @default.
• W2030796695 hasConceptScore W2030796695C134306372 @default.
• W2030796695 hasConceptScore W2030796695C139770010 @default.
• W2030796695 hasConceptScore W2030796695C150903083 @default.
• W2030796695 hasConceptScore W2030796695C170493617 @default.
• W2030796695 hasConceptScore W2030796695C185592680 @default.
• W2030796695 hasConceptScore W2030796695C197336794 @default.
• W2030796695 hasConceptScore W2030796695C207001950 @default.
• W2030796695 hasConceptScore W2030796695C2776297358 @default.
• W2030796695 hasConceptScore W2030796695C2776648616 @default.
• W2030796695 hasConceptScore W2030796695C2779281246 @default.
• W2030796695 hasConceptScore W2030796695C33923547 @default.
• W2030796695 hasConceptScore W2030796695C55493867 @default.
• W2030796695 hasConceptScore W2030796695C71924100 @default.
• W2030796695 hasConceptScore W2030796695C86803240 @default.
• W2030796695 hasConceptScore W2030796695C98274493 @default.
• W2030796695 hasIssue "2" @default.
• W2030796695 hasLocation W20307966951 @default.
• W2030796695 hasLocation W20307966952 @default.
• W2030796695 hasOpenAccess W2030796695 @default.
• W2030796695 hasPrimaryLocation W20307966951 @default.
• W2030796695 hasRelatedWork W1969594608 @default.
• W2030796695 hasRelatedWork W1974626719 @default.
• W2030796695 hasRelatedWork W1995607592 @default.
• W2030796695 hasRelatedWork W2040129605 @default.
• W2030796695 hasRelatedWork W2058985483 @default.
• W2030796695 hasRelatedWork W2069802714 @default.
• W2030796695 hasRelatedWork W2086608867 @default.
• W2030796695 hasRelatedWork W2088568642 @default.
• W2030796695 hasRelatedWork W2580675833 @default.
• W2030796695 hasRelatedWork W3199526661 @default.
• W2030796695 hasVolume "16" @default.
• W2030796695 isParatext "false" @default.

• next