Imaging the in vivo fate of human T cells following transplantation in immunoincompetent mice - implications for clinical cell therapy trials.
Many forms of adoptive T cell therapy are on the verge of being translated to the clinic. To gain further insight in their immunomodulating functions and to optimize future clinical trials it is essential to develop techniques to study their homing capacity. CD4+ T cells were labeled using [(111)In]oxine, and the radioactive uptake was determined in vitro before intravenous injection in immunodeficient mice. In vivo biodistribution of [(111)In]oxine-labeled cells or tracer alone was subsequently measured by μSPECT/CT and organ distribution. CD4+ T cells incorporated [(111)In]oxine with higher labeling yield using Ringer-Acetate compared to 0.9% NaCl. Cellular viability after labeling with [(111)In]oxine was not compromised using less than 0.4 MBq/million cells. After intravenous infusion CD4+ T cells preferentially homed to the liver (p<0.01) and spleen (p<0.05). This study presents a protocol for labeling of T cells by [(111)In]oxine with preserved viability and in vivo tracking by SPECT for up to 8days, which can easily be translated to clinical cell therapy trials.
Department of Immunology, Genetics and Pathology, Section of Clinical Immunology, Uppsala University, Sweden; Department of Surgical Sciences, Section of Transplantation Surgery, Uppsala University, Sweden. Electronic address: david.berglund@surgsci.uu.se.
David
D
Berglund
Marie
M
Karlsson
Senthilkumar
S
Palanisamy
Björn
B
Carlsson
Olle
O
Korsgren
Olof
O
Eriksson
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002986:Clinical Trials as Topic; D064593:Heterografts; D006801:Humans; D007204:Indium / Q000494:pharmacology*; D007205:Indium Radioisotopes / Q000494:pharmacology*; D051379:Mice; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D007205:Indium Radioisotopes; D007204:Indium
CM; CT; Cell therapy; In vivo imaging; MACS; PET; SPECT; SPECT/CT; T cell; complete media; computed tomography; magnetic activated cell sorting; positron emission tomography; single photon emission computed tomography