Document Detail

Synthesis of novel 68Ga-labeled amino acid derivatives for positron emission tomography of cancer cells.
MedLine Citation:
PMID:  21055619     Owner:  NLM     Status:  In-Process    
OBJECTIVES: We developed amino acid derivatives of 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A) and 1,4,7,10-tetraazacyclododecane-1,4,7,-triacetic acid (DO3A) that can be labeled with (68)Ga, and we investigated their basic biological properties.
MATERIALS AND METHODS: Alanine derivatives of DO2A and DO3A were synthesized by regiospecific nucleophilic attack of DO2tBu and DO3tBu on the β-position of Boc-l-serine-β-lactone, followed by acid hydrolysis. Also, homoalanine derivatives were synthesized by reacting with the protected bromo derivative of homoalanine, which was synthesized from N-Cbz-l-homoserine lactone. Further catalytic reduction and acid cleavage of protected groups resulted in the required products. All derivatives were labeled with (68)Ga. Cell uptake assays were carried out in Hep3B (human hepatoma) and U87MG (human glioma) cell lines at 37°C. Positron emission tomography (PET) imaging studies were performed using balb/c mice xenografted with CT-26 (mouse colon cancer).
RESULTS: All compounds were labeled with >97% efficiency. According to in vitro studies, the labeled amino acid derivatives showed significantly greater uptakes than the control ((68)Ga 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) in cancer cells. Small animal PET images for labeled compounds showed high tumor uptake, as well as kidney and bladder uptakes, at 30 min postinjection. (68)Ga-DO3A-homoalanine showed the highest standardized uptake value ratio (3.9 ± 0.3), followed by (68)Ga-DO2A-alanine (3.1 ± 0.2), (68)Ga-DO3A-alanine (2.8 ± 0.2) and (68)Ga-DO2A-homoalanine (2.3 ± 0.2).
CONCLUSION: These derivatives were found to have high labeling efficiencies, high stabilities, high tumor cell uptakes, high tumor/nontumor xenograft uptakes and low nonspecific uptake in normal organs, except for the kidneys. However, the uptake mechanism of these derivatives remains unclear, and uptake via specific amino acid transporters needs to be demonstrated.
Dinesh Shetty; Jae Min Jeong; Chang Hwan Ju; Yun-Sang Lee; Seo Young Jeong; Jae Yeon Choi; Bo Yeun Yang; Dong Soo Lee; June-Key Chung; Myung Chul Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-15
Journal Detail:
Title:  Nuclear medicine and biology     Volume:  37     ISSN:  1872-9614     ISO Abbreviation:  Nucl. Med. Biol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-08     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9304420     Medline TA:  Nucl Med Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  893-902     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744, South Korea.
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