64Cu-Labeled triphenylphosphonium and triphenylarsonium cations as highly tumor-selective imaging agents.
This report presents synthesis and evaluation of the 64Cu-labeled triphenylphosphonium (TPP) cations as new radiotracers for imaging tumors by positron emission tomography. Biodistribution properties of 64Cu-L1, 64Cu-L2, 64Cu-L3, and 99mTc-Sestamibi were evaluated in athymic nude mice bearing U87MG human glioma xenografts. The most striking difference is that 64Cu-L1, 64Cu-L2, and 64Cu-L3 have much lower heart uptake (<0.6% ID/g) than 99mTc-Sestamibi ( approximately 18% ID/g) at >30 min p.i. Their tumor/heart ratios increase steadily from approximately 1 at 5 min p.i. to approximately 5 at 120 min p.i. The tumor/heart ratio of 64Cu-L3 is approximately 40 times better than that of 99mTc-Sestamibi at 120 min postinjection. Results from in vitro assays show that 64Cu-L1 is able to localize in tumor mitochondria. The tumor is clearly visualized in the tumor-bearing mice administered with 64Cu-L1 as 30 min postinjection. The 64Cu-labeled TPP/TPA cations are very selective radiotracers that are able to provide the information of mitochondrial bioenergetic function in tumors by monitoring mitochondrial potential in a noninvasive fashion.
Wang
Jianjun
J
School of Health Sciences, Purdue University, West Lafayette, Indiana, USA.
Yang
Chang-Tong
CT
Kim
Young-Seung
YS
Sreerama
Subramanya G
SG
Cao
Qizhen
Q
Li
Zi-Bo
ZB
He
Zhengjie
Z
Chen
Xiaoyuan
X
Liu
Shuang
S
D000818:Animals; D001152:Arsenicals / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D002412:Cations; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D001152:Arsenicals; D001372:Aza Compounds; D002412:Cations; D003301:Copper Radioisotopes; D003510:Cyclohexanes; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals