Radiolabeling Human Peripheral Blood Stem Cells for Positron Emission Tomography (PET) Imaging in Young Rhesus Monkeys

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Abstract

These studies focused on a new radiolabeling technique with copper (64Cu) and zirconium (89Zr) for positron emission tomography (PET) imaging using a CD45 antibody. Synthesis of 64Cu-CD45 and 89Zr-CD45 immunoconjugates was performed and the evaluation of the potential toxicity of radiolabeling human peripheral blood stem cells (hPBSC) was assessed in vitro (viability, population doubling times, colony forming units). hPBSC viability was maintained as the dose of 64Cu-TETA-CD45 increased from 0 (92%) to 160 μCi/mL (76%, p>0.05). Radiolabeling efficiency was not significantly increased with concentrations of 64Cu-TETA-CD45 >20 μCi/mL (p>0.50). Toxicity affecting both growth and colony formation was observed with hPBSC radiolabeled with ≥40 μCi/mL (p<0.05). For 89Zr, there were no significant differences in viability (p>0.05), and a trend towards increased radiolabeling efficiency was noted as the dose of 89Zr-Df-CD45 increased, with a greater level of radiolabeling with 160 μCi/mL compared to 0-40 μCi/mL (p<0.05). A greater than 2,000 fold-increase in the level of 89Zr-Df-CD45 labeling efficiency was observed when compared to 64Cu-TETA-CD45. Similar to 64Cu-TETA-CD45, toxicity was noted when hPBSC were radiolabeled with ≥40 μCi/mL (p<0.05) (growth, colony formation). Taken together, 20 μCi/mL resulted in the highest level of radiolabeling efficiency without altering cell function. Young rhesus monkeys that had been transplanted prenatally with 25×106 hPBSC expressing firefly luciferase were assessed with bioluminescence imaging (BLI), then 0.3 mCi of 89Zr-Df-CD45, which showed the best radiolabeling efficiency, was injected intravenously for PET imaging. Results suggest that 89Zr-Df-CD45 was able to identify engrafted hPBSC in the same locations identified by BLI, although the background was high.

Original languageEnglish (US)
Article numbere77148
JournalPLoS One
Volume8
Issue number10
DOIs
StatePublished - Oct 3 2013

Fingerprint

positron-emission tomography
radiolabeling
Positron emission tomography
blood cells
Macaca mulatta
Stem cells
Positron-Emission Tomography
stem cells
Blood
image analysis
Imaging techniques
Bioluminescence
Toxicity
bioluminescence
toxicity
Immunoconjugates
Firefly Luciferases
Growth
Labeling
luciferase

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

@article{30ec3d707f44470b887d536d176b6ad2,
title = "Radiolabeling Human Peripheral Blood Stem Cells for Positron Emission Tomography (PET) Imaging in Young Rhesus Monkeys",
abstract = "These studies focused on a new radiolabeling technique with copper (64Cu) and zirconium (89Zr) for positron emission tomography (PET) imaging using a CD45 antibody. Synthesis of 64Cu-CD45 and 89Zr-CD45 immunoconjugates was performed and the evaluation of the potential toxicity of radiolabeling human peripheral blood stem cells (hPBSC) was assessed in vitro (viability, population doubling times, colony forming units). hPBSC viability was maintained as the dose of 64Cu-TETA-CD45 increased from 0 (92{\%}) to 160 μCi/mL (76{\%}, p>0.05). Radiolabeling efficiency was not significantly increased with concentrations of 64Cu-TETA-CD45 >20 μCi/mL (p>0.50). Toxicity affecting both growth and colony formation was observed with hPBSC radiolabeled with ≥40 μCi/mL (p<0.05). For 89Zr, there were no significant differences in viability (p>0.05), and a trend towards increased radiolabeling efficiency was noted as the dose of 89Zr-Df-CD45 increased, with a greater level of radiolabeling with 160 μCi/mL compared to 0-40 μCi/mL (p<0.05). A greater than 2,000 fold-increase in the level of 89Zr-Df-CD45 labeling efficiency was observed when compared to 64Cu-TETA-CD45. Similar to 64Cu-TETA-CD45, toxicity was noted when hPBSC were radiolabeled with ≥40 μCi/mL (p<0.05) (growth, colony formation). Taken together, 20 μCi/mL resulted in the highest level of radiolabeling efficiency without altering cell function. Young rhesus monkeys that had been transplanted prenatally with 25×106 hPBSC expressing firefly luciferase were assessed with bioluminescence imaging (BLI), then 0.3 mCi of 89Zr-Df-CD45, which showed the best radiolabeling efficiency, was injected intravenously for PET imaging. Results suggest that 89Zr-Df-CD45 was able to identify engrafted hPBSC in the same locations identified by BLI, although the background was high.",
author = "Tarantal, {Alice F} and Lee, {Charles C} and Kukis, {David L.} and Cherry, {Simon R}",
year = "2013",
month = "10",
day = "3",
doi = "10.1371/journal.pone.0077148",
language = "English (US)",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
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T1 - Radiolabeling Human Peripheral Blood Stem Cells for Positron Emission Tomography (PET) Imaging in Young Rhesus Monkeys

AU - Tarantal, Alice F

AU - Lee, Charles C

AU - Kukis, David L.

AU - Cherry, Simon R

PY - 2013/10/3

Y1 - 2013/10/3

N2 - These studies focused on a new radiolabeling technique with copper (64Cu) and zirconium (89Zr) for positron emission tomography (PET) imaging using a CD45 antibody. Synthesis of 64Cu-CD45 and 89Zr-CD45 immunoconjugates was performed and the evaluation of the potential toxicity of radiolabeling human peripheral blood stem cells (hPBSC) was assessed in vitro (viability, population doubling times, colony forming units). hPBSC viability was maintained as the dose of 64Cu-TETA-CD45 increased from 0 (92%) to 160 μCi/mL (76%, p>0.05). Radiolabeling efficiency was not significantly increased with concentrations of 64Cu-TETA-CD45 >20 μCi/mL (p>0.50). Toxicity affecting both growth and colony formation was observed with hPBSC radiolabeled with ≥40 μCi/mL (p<0.05). For 89Zr, there were no significant differences in viability (p>0.05), and a trend towards increased radiolabeling efficiency was noted as the dose of 89Zr-Df-CD45 increased, with a greater level of radiolabeling with 160 μCi/mL compared to 0-40 μCi/mL (p<0.05). A greater than 2,000 fold-increase in the level of 89Zr-Df-CD45 labeling efficiency was observed when compared to 64Cu-TETA-CD45. Similar to 64Cu-TETA-CD45, toxicity was noted when hPBSC were radiolabeled with ≥40 μCi/mL (p<0.05) (growth, colony formation). Taken together, 20 μCi/mL resulted in the highest level of radiolabeling efficiency without altering cell function. Young rhesus monkeys that had been transplanted prenatally with 25×106 hPBSC expressing firefly luciferase were assessed with bioluminescence imaging (BLI), then 0.3 mCi of 89Zr-Df-CD45, which showed the best radiolabeling efficiency, was injected intravenously for PET imaging. Results suggest that 89Zr-Df-CD45 was able to identify engrafted hPBSC in the same locations identified by BLI, although the background was high.

AB - These studies focused on a new radiolabeling technique with copper (64Cu) and zirconium (89Zr) for positron emission tomography (PET) imaging using a CD45 antibody. Synthesis of 64Cu-CD45 and 89Zr-CD45 immunoconjugates was performed and the evaluation of the potential toxicity of radiolabeling human peripheral blood stem cells (hPBSC) was assessed in vitro (viability, population doubling times, colony forming units). hPBSC viability was maintained as the dose of 64Cu-TETA-CD45 increased from 0 (92%) to 160 μCi/mL (76%, p>0.05). Radiolabeling efficiency was not significantly increased with concentrations of 64Cu-TETA-CD45 >20 μCi/mL (p>0.50). Toxicity affecting both growth and colony formation was observed with hPBSC radiolabeled with ≥40 μCi/mL (p<0.05). For 89Zr, there were no significant differences in viability (p>0.05), and a trend towards increased radiolabeling efficiency was noted as the dose of 89Zr-Df-CD45 increased, with a greater level of radiolabeling with 160 μCi/mL compared to 0-40 μCi/mL (p<0.05). A greater than 2,000 fold-increase in the level of 89Zr-Df-CD45 labeling efficiency was observed when compared to 64Cu-TETA-CD45. Similar to 64Cu-TETA-CD45, toxicity was noted when hPBSC were radiolabeled with ≥40 μCi/mL (p<0.05) (growth, colony formation). Taken together, 20 μCi/mL resulted in the highest level of radiolabeling efficiency without altering cell function. Young rhesus monkeys that had been transplanted prenatally with 25×106 hPBSC expressing firefly luciferase were assessed with bioluminescence imaging (BLI), then 0.3 mCi of 89Zr-Df-CD45, which showed the best radiolabeling efficiency, was injected intravenously for PET imaging. Results suggest that 89Zr-Df-CD45 was able to identify engrafted hPBSC in the same locations identified by BLI, although the background was high.

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