RT Journal Article
SR Electronic
T1 In vivo imaging of long term stem cell trafficking/engraftment is enabled by a human somatostatin receptor type-2 (hSSTR2) mutant that has the desirable features of being muted in altering stem cell signaling and function
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 633
OP 633
VO 50
IS supplement 2
A1 Singh, Sheela P.
A1 Han, Lin
A1 Ravoori, Murali
A1 Harris, David
A1 Estrov, Zeev
A1 Kundra, Vikas
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/633.abstract
AB 633 Objectives Following long term stem cell trafficking and engraftment is important for understanding their fate and therapeutic potential. Reporters (enzymes, transporters, receptors) can alter cellular milieu/function. We tested whether a hSSTR2 mutant is signaling deficient in stem cells and can serve to image these cells in vivo. Methods HS5 human mesenchymal stem cells were stably transfected with hemagglutinin A (HA) tagged-hSSTR2, mutant receptor or vector. cGMP and cAMP production as well as growth inhibition in response to ligand were tested. Differentiation was tested. In vivo, 6 mice were injected subQ with HS5 cells transfected with HA-SSTR2, mutant or vector and HeyA8 ovarian cancer cells. 3 weeks later, imaging was performed with FDA approved 111In-octreotide. To assess trafficking and engraftment, transfected HS5 cells were instead given intracardiac 1 day after subQ HeyA8 injection. Results Mutant receptor did not elicit cGMP production, inhibit forskolin-induced cAMP production or inhibit growth in response to ligand; whereas, wild-type receptor did. HS5 cells expressing either receptor differentiated into bone and fat-like cells. In vivo, after co-injection or HS5 systemic injection, HeyA8 tumors incorporating HS5 cells expressing mutant or wild-type receptor showed increased uptake. Ex vivo biodistribution analysis confirmed results (P<.05 mutant or wild-type vs vector). Conclusions A hSSTR2 mutant, that has the desirable features of being muted in altering stem cell signaling and function, can serve as a reporter of long term stem cell trafficking/engraftment.