title: Differential biodistribution of intravenously administered endothelial progenitor and cytotoxic T-cells in rat bearing orthotopic human glioma.
abstract: BACKGROUND
  A major challenge in the development of cell based therapies for glioma is to deliver optimal number of cells (therapeutic dose) to the tumor. Imaging tools such as magnetic resonance imaging (MRI), optical imaging, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) has been used in cell tracking and/or biodistribution studies. In this study, we evaluate the dynamic biodistribution of systemic injected labeled cells [human cord blood derived endothelial progenitor cells (EPCs) and cytotoxic T-cells (CTLs)] in rat glioma model with in vivo SPECT imaging.
  
  
  METHODS
  Human cord blood EPCs, T-cells and CD14⁺ cells (monocytes/dendritic cells) were isolated using the MidiMACS system. CD14⁺ cells were converted to dendritic cells (DC) and also primed with U251 tumor cell line lysate. T-cells were co-cultured with irradiated primed DCs at 10:1 ratio to make CTLs. Both EPCs and CTLs were labeled with In-111-oxine at 37°C in serum free DMEM media. Glioma bearing animals were randomly assigned into three groups. In-111 labeled cells or In-111 oxine alone were injected through tail vein and SPECT imaging was performed on day 0, 1, and 3. In-111 oxine activity in various organs and tumor area was determined. Histochemical analysis was performed to further confirm the migration and homing of injected cells at the tumor site.
  
  
  RESULTS
  EPCs and CTLs showed an In-111 labeling efficiency of 87.06 ± 7.75% and 70.8 ± 12.9% respectively. Initially cell migration was observed in lung following inravenous administration of In-111 labeled cells and decreased on day 1 and 3, which indicate re-distribution of labeled cells from lung to other organs. Relatively higher In-111 oxine activity was observed in tumor areas at 24 hours in animals received In-111 labeled cells (EPCs or CTLs). Histiological analysis revealed iron positive cells in and around the tumor area in animals that received labeled cells (CTLs and EPCs).
  
  
  CONCLUSIONS
  We observed differential biodistribution of In-111-oxine labeled EPCs and CTLs in different organs and intracranial glioma. This study indicates In-111 oxine based SPECT imaging is an effective tool to study the biodistribution of therapeutically important cells.
authors.affiliation: Cellular and Molecular Imaging Laboratory, Radiology, Henry Ford Hospital, Detroit, MI, USA. ravin@rad.hfh.edu
authors.forename: Nadimpalli Ravi S
authors.initials: NR
authors.lastname: Varma
authors.forename: Adarsh
authors.initials: A
authors.lastname: Shankar
authors.forename: Asm
authors.initials: A
authors.lastname: Iskander
authors.forename: Branislava
authors.initials: B
authors.lastname: Janic
authors.forename: Thaiz Ferraz
authors.initials: TF
authors.lastname: Borin
authors.forename: Meser M
authors.initials: MM
authors.lastname: Ali
authors.forename: Ali S
authors.initials: AS
authors.lastname: Arbab
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D058948:Cell Tracking / Q000379:methods; D005910:Glioma / Q000000981:diagnostic imaging* / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000000981:diagnostic imaging*; D006801:Humans; D051381:Rats; D011923:Rats, Nude; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000000981:diagnostic imaging* / Q000637:transplantation*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*