RT Journal Article
SR Electronic
T1 Preparation and evaluation of <sup>99m</sup>Tc-labeled dimeric Tyr<sup>3</sup>-Octreotide in the AR42J tumor model
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1472
OP 1472
VO 52
IS supplement 1
A1 Dong, Chengyan
A1 Zhao, Huiyun
A1 Cui, Liyang
A1 Shi, Jiyun
A1 Huang, Jinming
A1 Yang, Sujuan
A1 Liu, Zhaofei
A1 Jia, Bing
A1 Wang, Fan
YR 2011
UL http://jnm.snmjournals.org/content/52/supplement_1/1472.abstract
AB 1472 Objectives There is an increasing interest in the development of radiolabeled multivalent ligands due to the higher tumor uptake than the corresponding monomer. This report presents the synthesis of a Tyr3-Octreotide dimer conjugate, HYNIC-E[Tyr3-Octreotide]2 (HYNIC-TOC2), and the biological evaluation in the AR42J tumor model. Methods NH2-E[Tyr3-Octreotide]2 was synthesized and conjugated with a bifunctional chelator HYNIC. The binding affinity of HYNIC-TOC2 to SSTR2 was determined in the AR42J rat pancreatic cancer cells, using 125I-Tyr3-octreotide as the radiotracer. 99mTc-HYNIC-TOC2 was prepared by using tricine and EDDA as coligands. The biodistribution and γ imaging were performed in nude mice bearing AR42J tumors. Results 99mTc-HYNIC-TOC2 was obtained with &gt; 95% labeling yield and favorable stability. Compared with 99mTc-HYNIC-TOC, 99mTc-HYNIC-TOC2 showed significantly increased tumor uptake (13.31 ± 3.14 %ID/g vs 5.32 ± 0.94 %ID/g, 12.05 ± 2.92% ID/g vs 5.01 ± 1.15 %ID/g at 1 h and 4 h p.i., respectively). Although the accumulation of 99mTc-HYNIC-TOC2 in kidneys was also significantly increased (94.40 ± 6.51 %ID/g vs 32.27 ± 4.51 %ID/g at 1 h p.i.), this high uptake was inhibited by the injection of L-lysine before the administration of 99mTc-HYNIC-TOC2 (30.99 ± 5.05 %ID/g at 1 h p.i.). In vivo planar γ imaging showed that the tumors were clearly visualized, while the background signal was much lower except for the kidneys and bladder. Conclusions These data merit the translation of 99mTc-HYNIC-TOC2 to clinical setting. The higher tumor uptake of 99mTc-HYNIC-TOC2 suggests that 90Y/177Lu-labeled TOC2 might have advantage for the radiotherapy of SSTR2- positive tumors. Research Support NSFC projects (30870728, 30930030, 30900373, and 81000625), an “863” project (2007AA02Z467), a “973” project (2011CB707703), and grants from the Ministry of Science and Technology of China (2009ZX09103-733, 2009ZX09301-010 and 2009ZX09103-746)