RT Journal Article
SR Electronic
T1 SPECT and optical multimodality imaging of HIF-active tumors by using an oxygen-dependent degradation protein probe with interchangeable labeling system
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1723
OP 1723
VO 52
IS supplement 1
A1 Umeda, Izumi
A1 Kakishima, Yuu
A1 Kimura, Sadaaki
A1 Yamaguchi, Masayuki
A1 Kuchimaru, Takahiro
A1 Kizaka-Kondoh, Shinae
A1 Yanaka, Akinori
A1 Fujii, Hirofumi
YR 2011
UL http://jnm.snmjournals.org/content/52/supplement_1/1723.abstract
AB 1723 Objectives The visualization of hypoxia-inducible factor (HIF)-active tumors is clinically important. We designed a novel in vivo imaging probe for it that consists of protein transduction domain, oxygen-dependent degradation domain, and HaloTag® protein (POH). It can be used as a probe for various imaging modality by differently labeled HaloTag® ligands (HL). We have already succeeded in monitoring HIF-active region in cancers with the near-infrared fluorescently labeled POH probe (NIRF-POH). In this study, we labeled POH with 111In and evaluated their biodistribution in the tumor-bearing mice and their in vivo SPECT images, comparing with NIRF-POH. Methods HL-DOTA and HL-BnDOTA were synthesized by the reaction of HL-NH2 and NHS-DOTA or p-SCN-BnDOTA, and purified on ODS. They were labeled with 111In, and then conjugated to POH. These radioactive probes were injected i.v. to mice with FM3A or Suit-2 tumors. Results Both HL-DOTAs were labeled with 111In showing good radiochemical yield (~80%). Conjugation of 111In-HL-DOTAs to POH (111In-POH) was confirmed as a single band around 46 kDa by SDS-PAGE. Their radiochemical purity was over 95%. The biodistribution of 111In-POH was similar to that of NIRF-POH and 111In-POH well accumulated in both tumors (0.8-2.6 % administered dose/g) at 24 h after injection. On in vivo SPECT images, POH was distributed strongly in the liver and kidney, but tumors could be identified at 1h after i.v.. And, as the activities of background areas as well as liver and kidneys gradually decreased, tumors were more clearly visualized at 24 h. Conclusions 111In-POH showed similar biodistribution to NIRF-POH. And, they could provide quantitative biodistribution data. Moreover, they were clearly imaged on in vivo SPECT for the first time. The SPECT and optical dual imaging system studied here would promote the clinical translation of our HIF imaging strategy established by animal experiments using NIRF-POH