当前位置： SCI文献检索 > NUCLEAR MEDICINE AND BIOLOGY期刊下所有文献 > Investigation into 64Cu-labeled Bis(selenosemicarbazone) and Bis(thiosemicarbazone) complexes as hypoxia imaging agents.

Investigation into 64Cu-labeled Bis(selenosemicarbazone) and Bis(thiosemicarbazone) complexes as hypoxia imaging agents.

Abstract：

BACKGROUND:Cu-diacetyl-bis(N4-methylthiosemicarbazone) [Cu-ATSM], although excellent for oncology applications, may not be suitable for delineating cardiovascular or neurological hypoxia. For this reason, new Cu hypoxia positron emission tomography (PET) imaging agents are being examined to search for a higher selectivity for hypoxic or ischemic tissue at higher oxygen concentrations found in these tissues. Two approaches are to increase alkylation or to replace the sulfur atoms with selenium, resulting in the formation of selenosemicarbazones. METHODS:Three 64Cu-labeled selenosemicarbazone complexes were synthesized and one was screened for hypoxia selectivity in vitro using EMT-6 mouse mammary carcinoma cells. Rodent biodistribution and small animal PET images were obtained from BALB/c mice implanted with EMT-6 tumors. One alkylated thiosemicarbazone was synthesized and examined. RESULTS:Of the three bis(selenosemicarbazone) ligands synthesized and examined, only 64Cu-diacetyl-bis(selenosemicarbazone) [64Cu-ASSM] was isolated in high-enough radiochemical purity to undertake cell uptake experiments where uptake was shown to be independent of oxygen concentration. The bis(thiosemicarbazone) complex synthesized, 64Cu-diacetyl-bis(N4-ethylthiosemicarbazone) [64Cu-ATSE], showed hypoxia selectivity similar to 64Cu-ATSM although at a higher oxygen concentration. Biodistribution studies for 64Cu-ASSM and 64Cu-ATSE showed high tumor uptake at 20 min (64Cu-ASSM, 10.33+/-0.78% ID/g; 64Cu-ATSE, 7.71+/-0.46% ID/g). PET images of EMT-6 tumor-bearing mice visualized the tumor with 64Cu-ATSE and revealed hypoxia selectivity consistent with the in vitro data. CONCLUSION:Of the compounds synthesized, only 64Cu-ASSM and 64Cu-ATSE could be examined in vitro and in vivo. Although the stability of bis(selenosemicarbazone) complexes increased upon addition of methyl groups to the diimine backbone, the fully alkylated species, 64Cu-ASSM, demonstrated no hypoxia selectivity. However, the additional alkylation present in Cu-ATSE modifies the hypoxia selectivity and in vivo properties when compared with Cu-ATSM.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

McQuade P,Martin KE,Castle TC,Went MJ,Blower PJ,Welch MJ,Lewis JS

doi

10.1016/j.nucmedbio.2004.10.004

keywords:

subject

Has Abstract

pub_date

2005-02-01 00:00:00

pages

147-56

issue

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(04)00169-6

journal_volume

pub_type

杂志文章

在线工具

Investigation into 64Cu-labeled Bis(selenosemicarbazone) and Bis(thiosemicarbazone) complexes as hypoxia imaging agents.