Catabolism of (64)Cu and Cy5.5-labeled human serum albumin in a tumor xenograft model.
Human serum albumin (HSA), the most abundant protein in blood plasma, has been used as a drug carrier for the last few decades. Residualizingly radiolabeled serum albumin has been reported to be avidly taken up by tumors of sarcoma-bearing mice and to most likely undergo lysosomal degradation. In this study, we prepared (64)Cu-1,4,7,10-tetraazacyclododecane-N,N',N″,N'″-tetraacetic acid (DOTA) and Cy5.5-conjugated HSA (dual probe), and evaluated its tumor uptake and catabolism. Two dual probes were prepared using different DOTA conjugation sites of HSA (one via Lys residues and the other via the Cys residue). (64)Cu-DOTA-Lys-HSA-Cy5.5 (dual probe-Lys) exhibited higher uptake by RR1022 sarcoma cells in vitro than (64)Cu-DOTA-Cys-HSA-Cy5.5 (dual probe-Cys). In RR1022 tumor-bearing mice, the two dual probes showed a similar level of tumor uptake, but uptake of dual probe-Lys was reduced in the liver and spleen compared to dual probe-Cys, probably because of the presence of a higher number of DOTA molecules in the former. At 24 and 48 h after injection, dual probe-Lys was intact or partially degraded in blood, liver, kidney, and tumor samples, but (64)Cu-DOTA-Lys was observed in the urine using radioactivity detection. Similarly, Cy5.5-Lys was observed in the urine using fluorescence detection. These results indicate that dual probe-Lys may be useful for predicting the catabolic fate of drug-HSA conjugates.
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Korea.
Choong Mo
CM
Kang
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Korea.
Hyunjung
H
Kim
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
Hyun-Jung
HJ
Koo
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Korea.
Jin Won
JW
Park
Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, Korea.
Gwang Il
GI
An
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
Joon Young
JY
Choi
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Korea.
Kyung-Han
KH
Lee
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
Byung-Tae
BT
Kim
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea. ysnm.choe@samsung.com.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Korea. ysnm.choe@samsung.com.
Yearn Seong
YS
Choe
D000818:Animals; D002232:Carbocyanines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D064593:Heterografts; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D000075462:Serum Albumin, Human / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D003300:Copper; D000075462:Serum Albumin, Human
64Cu-DOTA-Lys; Catabolism; Cy5.5-Lys; Human serum albumin; PET/optical imaging; Tumor