Micro-PET imaging of beta-glucuronidase activity by the hydrophobic conversion of a glucuronide probe.
OBJECTIVE
To develop a new glucuronide probe for micro-positron emission topography (PET) that can depict beta-glucuronidase (betaG)-expressing tumors in vivo.


METHODS
All animal experiments were preapproved by the Institutional Animal Care and Use Committee. A betaG-specific probe was generated by labeling phenolphthalein glucuronide (PTH-G) with iodine 131 ((131)I) or (124)I. To test the specificity of the probe in vitro, (124)I-PTH-G was added to CT26 and betaG-expressing CT26 (CT26/betaG) cells. Mice bearing CT26 and CT26/betaG tumors (n = 6) were injected with (124)I-PTH-G and subjected to micro-PET imaging. A betaG-specific inhibitor D-saccharic acid 1,4-lactone monohydrate was used in vitro and in vivo to ascertain the specificity of the glucuronide probes. Finally, the biodistributions of the probes were determined in selected organs after injection of (131)I-PTH-G to mice bearing CT26 and CT26/betaG tumors (n = 14). Differences in the radioactivity in CT26 and CT26/betaG tumors were analyzed with the Wilcoxon signed rank test.


RESULTS
(124)I-PTH-G was selectively converted to (124)I-PTH (phenolphthalein), which accumulated in CT26/betaG cells and tumors in vitro. The micro-PET images demonstrated enhanced activity in CT26/betaG tumors resulting from betaG-mediated conversion and trapping of the radioactive probes. Accumulation of radioactive signals was 3.6-, 3.4-, and 3.3-fold higher in the CT26/betaG tumors than in parental CT26 tumors at 1, 3, and 20 hours, respectively, after injection of the probe (for all the three time points, P < .05).


CONCLUSIONS
Hydrophilic-hydrophobic conversion of (124)I-PTH-G probe can aid in imaging of betaG-expressing tumors in vivo.
Tzou
Shey-Cherng
SC
Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.
Roffler
Steve
S
Chuang
Kuo-Hsiang
KH
Yeh
Hsin-Pei
HP
Kao
Chien-Han
CH
Su
Yu-Cheng
YC
Cheng
Chiu-Min
CM
Tseng
Wei-Lung
WL
Shiea
Jentaie
J
Harm
I-Hong
IH
Cheng
Kai-Wen
KW
Chen
Bing-Mae
BM
Hwang
Jeng-Jong
JJ
Cheng
Tian-Lu
TL
Wang
Hsin-Ell
HE
D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000201:enzymology*; D005260:Female; D005966:Glucuronidase / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental; D010635:Phenolphthaleins; D049268:Positron-Emission Tomography / Q000379:methods; D018709:Statistics, Nonparametric
D007457:Iodine Radioisotopes; D010635:Phenolphthaleins; C016651:phenolphthalein glucuronide; D005966:Glucuronidase