FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1837763205> ?p ?o ?g. }

• W1837763205 abstract "The growth in biotechnology has led to new techniques for the design, selection and production of ligands capable of molecular recognition. One promising approach is the production of specific receptor binding molecules based on specific nucleic acid sequences that are capable of recognising a wide array of target molecules. These oligonuclide ligands are known as aptamers (1.2). The technology that allows production of aptamer molecules is known as systematic evolution of ligands by exponential enrichment (SELEX). We have used combinatorial chemistry techniques coupled with polymerase chain reaction (PCR) to rapidly select aptamers from degenerate libraries that bind with high affinity and specificity to the protein core of the MUC1 antigen, a tumour marker previously extensively used in tumour imaging and therapy. MUC1 is widely expressed by normal glandular epithelial cells. However this expression is dramatically increased when the cells become malignant. This has been well documented for breast and ovarian cancer, as well as some lung, pancreatic and prostate cancers (3). Recently it has also been shown that MUC1 is a valuable marker for bladder and has been used for the imaging and targeted therapy of bladder cancer.The aptamer selection process was performed on affinity chromatography matrices. After ten rounds of selection and amplification, aptamers were cloned and sequenced. Post SELEX amino modifications have been used to confer nuclease resistance and coupling potential. The aptamers bound to MUC1 antigen with a Kd of 5nm and high specificity, demonstrated by fluorescent microscopy on MUC1-expresing tumour cells. Using peptide coupling reactions, we have successfully attached chelators for Tc-99m radiolabelling. Two of the constructs tested were based on mono-aptamer chelator complexes, one with commercially available MAG3 and one with a novel designed cyclen-based chelator. The other two constructs were based on the use of multi-aptamer complexes, where four aptamers were attached to the four arms of either DOTA or carboxy-porphyrin. The four complexes were labelled with Tc-99m and tested for their efficacy as tumour imaging agents. All four complexes demonstrated specificity for the tumour, due to their MUC1 specificity, at various levels. Biodistribution studies were carried out in mice with MCF7 xenografts. The monomeric aptamer complexes had rapid renal clearance from the system, due to their small size (MW of 8,000 Da). More than 90% of the aptamer based radiopharmaceutical was cleared from the system within the first 15 minutes. To increase retention time, additional constructs based on the design of a tetra-aptamer complex were prepared. A core chelator, such as DOTA and carboxy-porphyrin has been used as a skeleton for the building of multiaptamer constructs aiming to increase the molecular weight of the complex and potentially its stability of binding due to interactions with more than one MUC1 molecules at the surface of the tumour cell. The increase of the MW to 32,000 Da allowed increased retention times in the system, without compromising the exceptional tumour penetration exhibited by all the aptamer based constructs under study.The development of aptamers as small building blocks for targeting agents offers several advantages. These molecules penetrate tumour more readily than whole antibodies, reach peak levels in the tumour more rapidly and clear from the body faster, thereby reducing toxicity to healthy tissues. Our strategy is to manipulate the molecular weight of the construct utilising previously devised methodologies to achieve various polymeric aptamer complexes in order to achieve the optimum balance between the low immunogenicity and excellent tumour penetration. In this way we aim to achieve a balance against the rapid renal clearance that leads to premature elimination of the complex from the system and adequate tumour uptake for diagnostic imaging and targeted therapy. We intend to undertake further work using Re-188 to produce a therapeutic aptamer conjugate." @default.
• W1837763205 created "2016-06-24" @default.
• W1837763205 creator A5034061803 @default.
• W1837763205 creator A5086810315 @default.
• W1837763205 date "2005-04-01" @default.
• W1837763205 modified "2023-09-26" @default.
• W1837763205 title "Radiolabelled aptamers for imaging and therapy" @default.
• W1837763205 hasPublicationYear "2005" @default.
• W1837763205 type Work @default.
• W1837763205 sameAs 1837763205 @default.
• W1837763205 citedByCount "0" @default.
• W1837763205 crossrefType "book-chapter" @default.
• W1837763205 hasAuthorship W1837763205A5034061803 @default.
• W1837763205 hasAuthorship W1837763205A5086810315 @default.
• W1837763205 hasConcept C104317684 @default.
• W1837763205 hasConcept C122682173 @default.
• W1837763205 hasConcept C128972844 @default.
• W1837763205 hasConcept C153911025 @default.
• W1837763205 hasConcept C179264091 @default.
• W1837763205 hasConcept C185592680 @default.
• W1837763205 hasConcept C24107716 @default.
• W1837763205 hasConcept C2777421810 @default.
• W1837763205 hasConcept C502942594 @default.
• W1837763205 hasConcept C55493867 @default.
• W1837763205 hasConcept C67705224 @default.
• W1837763205 hasConcept C70721500 @default.
• W1837763205 hasConcept C86803240 @default.
• W1837763205 hasConceptScore W1837763205C104317684 @default.
• W1837763205 hasConceptScore W1837763205C122682173 @default.
• W1837763205 hasConceptScore W1837763205C128972844 @default.
• W1837763205 hasConceptScore W1837763205C153911025 @default.
• W1837763205 hasConceptScore W1837763205C179264091 @default.
• W1837763205 hasConceptScore W1837763205C185592680 @default.
• W1837763205 hasConceptScore W1837763205C24107716 @default.
• W1837763205 hasConceptScore W1837763205C2777421810 @default.
• W1837763205 hasConceptScore W1837763205C502942594 @default.
• W1837763205 hasConceptScore W1837763205C55493867 @default.
• W1837763205 hasConceptScore W1837763205C67705224 @default.
• W1837763205 hasConceptScore W1837763205C70721500 @default.
• W1837763205 hasConceptScore W1837763205C86803240 @default.
• W1837763205 hasLocation W18377632051 @default.
• W1837763205 hasOpenAccess W1837763205 @default.
• W1837763205 hasPrimaryLocation W18377632051 @default.
• W1837763205 hasRelatedWork W1985829704 @default.
• W1837763205 hasRelatedWork W2001447389 @default.
• W1837763205 hasRelatedWork W2012906571 @default.
• W1837763205 hasRelatedWork W2015877548 @default.
• W1837763205 hasRelatedWork W2046802601 @default.
• W1837763205 hasRelatedWork W2056150293 @default.
• W1837763205 hasRelatedWork W2122970542 @default.
• W1837763205 hasRelatedWork W2149904729 @default.
• W1837763205 hasRelatedWork W2207492336 @default.
• W1837763205 hasRelatedWork W2274174847 @default.
• W1837763205 hasRelatedWork W2322109414 @default.
• W1837763205 hasRelatedWork W2578909005 @default.
• W1837763205 hasRelatedWork W2604162431 @default.
• W1837763205 hasRelatedWork W2735593923 @default.
• W1837763205 hasRelatedWork W2773811223 @default.
• W1837763205 hasRelatedWork W2784581157 @default.
• W1837763205 hasRelatedWork W2913040802 @default.
• W1837763205 hasRelatedWork W3046237604 @default.
• W1837763205 hasRelatedWork W3153279919 @default.
• W1837763205 hasRelatedWork W3198929454 @default.
• W1837763205 isParatext "false" @default.
• W1837763205 isRetracted "false" @default.
• W1837763205 magId "1837763205" @default.
• W1837763205 workType "book-chapter" @default.