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- W74559951 abstract "1483 Objectives AS1411 is a guanine-rich oligonucleotide that binds with high affinity and specificity to nucleolin, a protein over-expressed in multiple cancer cells. We previously reported the effect of four chelators on the uptake of Cu-64 labeled AS1411 in HTB177 cells. Thus the objective of this study was to perform target validation for Cu-64 labeled AS1411. Methods A cytosine-rich oligonucleotide (CRO) was used as a control. Either DOTA (1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid mono N-hydroxysuccinimide ester) or CB-TE2A (tetraazamacrocycle 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane) was used to label AS1411 (DA or CBA) and CRO (DC or CBC) with Cu-64. HTB177 cells (2×105) were seeded into each well (n=6 for each condition). Different amount of AS1411 (0, 0.1, 1 and 10 nmoles) was added as a blocking agent and then incubated at 37 oC for 24 h. Afterward, the medium was removed, 3 µCi of DA, DC, CBA, or CBC was added and remained for 24 h. The effect of AS1411 on cell growth was studied separately. Results Specific activity for DA, CBA, DC, and CBC was 69, 30, 101, and 33 mCi/µmol respectively. Regardless of the amount of AS1411 added, uptake for both DC and CBC was similar ( 0.05). Uptake of DA and CBA was inversely proportional to the amount of AS1411 present, with 70% and 60% reduction at 10 nmoles. Cell growth and viability were unaffected in cells incubated with up to 50 nmoles of AS1411 for 24 h. Conclusions Uptake for both control oligonucleotides, DC and CBC, could be attributed to non-specific binding. Thus the specific binding of DA and CBA to the target protein was at least 60%, indicating that they might be a novel PET imaging probe targeting lung cancer" @default.
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- W74559951 date "2010-05-01" @default.
- W74559951 modified "2023-09-25" @default.
- W74559951 title "Target validation of Cu-64 labeled aptamer, AS1411, in lung cancer" @default.
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