Imaging hNET reporter gene expression with 124I-MIBG Journal Article

Authors: Moroz, M. A.; Serganova, I.; Zanzonico, P.; Ageyeva, L.; Beresten, T.; Dyomina, E.; Burnazi, E.; Finn, R. D.; Doubrovin, M.; Blasberg, R. G.
Article Title: Imaging hNET reporter gene expression with 124I-MIBG
Abstract: The norepinephrine transporter (NET) has recently been suggested as a useful reporter gene. We have extended this effort by constructing an internal ribosomal entry site (IRES)-linked hNET-green fluorescent protein (GFP) hybrid reporter gene for both nuclear and optical imaging. Methods: A retroviral vector pQCXhNET-IRES-GFP was constructed and used to generate several reporter cell lines and xenografts. Transduced cells were sorted by fluorescence-activated cell sorting based on GFP expression and used for both in vitro and in vivo imaging studies. Results: The transduced reporter cells accumulated 123I- or 124I-labeled metaiodobenzylguanidine (MIBG) to high levels compared with the wild-type parent cell lines. Differences in MIBG accumulation between cell lines were primarily due to differences in influx (K1) rather than efflux (k2). The estimated MIBG distribution volumes (Vd) for transduced Jurkat, C6, and COS-7 cells were 572 ± 13, 754 ± 25, and 1,556 ± 38 mL/g, respectively. A correlation between radiotracer accumulation (K1) and GFP fluorescence intensity was also demonstrated. Sequential imaging studies of mice bearing pQCXhNET-IRES-GFP transduced and wild-type C6 xenografts demonstrated several advantages of 124I-MIBG small-animal PET compared with 123I-MIBG γ-camera/SPECT. This was primarily due to the longer half-life of 124I and to the retention and slow clearance (half-time, 63 ± 6 h) of MIBG from transduced xenografts compared with that from wild-type xenografts (half-time, 12 ± 1 h) and other organs (half-time, 2.6-21 h). Very high radioactivity ratios were observed at later imaging times; at 73 h after 124I-MIBG injection, the C6/hNET-IRES-GFP xenograft-to-muscle ratiowas 293 ± 48 whereas the C6 xenograft-to-muscle ratiowas 0.71 ± 0.19. Conclusion: These studies demonstrate the potential for a wider application of hNET reporter imaging and the future translation to patient studies using radiopharmaceuticals that are currently available for both SPECT and PET. Copyright © 2007 by the Society of Nuclear Medicine, Inc.
Keywords: controlled study; protein expression; unclassified drug; human cell; genetics; nonhuman; positron emission tomography; radiopharmaceuticals; animal cell; mouse; animal; metabolism; animals; mice; animal tissue; gene expression; gene expression profiling; green fluorescent protein; animal experiment; molecular imaging; physiology; diagnostic agent; nude mouse; tissue distribution; mice, nude; whole body imaging; rat; radioactivity; retrovirus vector; radiopharmaceutical agent; (3 iodobenzyl)guanidine; noradrenalin transporter; reporter gene; 3-iodobenzylguanidine; norepinephrine plasma membrane transport proteins; drug clearance; genes, reporter; drug half life; single photon emission computer tomography; pet; fluorescence activated cell sorting; spect; internal ribosome entry site; γ-camera; 123i-mibg; 124i-mibg; human norepinephrine transporter; metaiodobenzylguanidine i 123; metaiodobenzylguanidine i 124
Journal Title: Journal of Nuclear Medicine
Volume: 48
Issue: 5
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2007-05-01
Start Page: 827
End Page: 836
Language: English
DOI: 10.2967/jnumed.106.037812
PUBMED: 17475971
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 31" - "Export Date: 17 November 2011" - "CODEN: JNMEA" - "Source: Scopus"
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MSK Authors
  1. Ronald G Blasberg
    244 Blasberg
  2. Ronald D Finn
    252 Finn
  3. Eva M Burnazi
    13 Burnazi
  4. Pat B Zanzonico
    246 Zanzonico
  5. Maxim A Moroz
    22 Moroz
  6. Ekaterina Matveevna Dyomina
    13 Dyomina
  7. Lyudmila Ageyeva
    31 Ageyeva