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A 4-methyl-substituted meta-iodobenzylguanidine analogue with prolonged retention in human neuroblastoma cells.

Publication ,  Journal Article
Vaidyanathan, G; Welsh, PC; Vitorello, KC; Snyder, S; Friedman, HS; Zalutsky, MR
Published in: Eur J Nucl Med Mol Imaging
October 2004

PURPOSE: As a part of our efforts to develop a meta-iodobenzylguanidine (MIBG) analogue with improved characteristics for the diagnosis and treatment of neuroendocrine tumours, 3-[131I]iodo-4-methyl-benzylguanidine ([131I]MeIBG) has been developed. The purpose of this study was to evaluate [131I]MeIBG in vitro using the uptake-1 positive SK-N-SH neuroblastoma cell line and in vivo in normal mice and mice bearing human neuroblastoma xenografts. METHODS: The ability of SK-N-SH human neuroblastoma cells to retain [131I]MeIBG in vitro over a period of 4 days, in comparison to [125I]MIBG, was determined by a paired-label assay. Paired-label biodistributions of [131I]MeIBG and [125I]MIBG were performed in normal mice as well as in athymic mice bearing SK-N-SH and IMR-32 human neuroblastoma xenografts. RESULTS: Retention of [131I]MeIBG by SK-N-SH cells in vitro was increased by factors of 1.2, 1.5, 2.0, 2.5 and 3.1 compared with [125I]MIBG at 8, 24, 48, 72 and 96 h, respectively. In normal mice, the uptake of [131I]MeIBG in the heart was similar to that of [125I]MIBG at 1 and 4 h; in contrast, myocardial uptake of [131I]MeIBG was 1.6-fold higher than that of [125I]MIBG (p<0.05) at 24 h. When mice were pre-treated with the uptake-1 inhibitor desipramine (DMI), the heart uptake of both tracers was reduced to about half that in untreated controls at 1 h post injection (p<0.05). The hepatic uptake of [131I]MeIBG was two- to threefold lower than that of [125I]MIBG. On the other hand, blood levels of [131I]MeIBG were substantially higher (up to sixfold), especially at early time points. Uptake of [131I]MeIBG in heart and tumour at 1 h in the murine SK-N-SH model was specific and comparable to that of [125I]MIBG. However, [131I]MeIBG uptake was 1.6- to 1.7-fold lower than that of [125I]MIBG over 4-48 h. While the uptake of both tracers in IMR32 xenografts was similar, it was not uptake-1 mediated. CONCLUSION: Introduction of a methyl group at the 4-position of MIBG seems to be advantageous in terms of higher tumour retention in vitro and lower hepatic uptake in vivo. However, the slower blood clearance of MeIBG may be problematic for some applications.

Duke Scholars

Published In

Eur J Nucl Med Mol Imaging

DOI

ISSN

1619-7070

Publication Date

October 2004

Volume

31

Issue

10

Start / End Page

1362 / 1370

Location

Germany

Related Subject Headings

  • Tissue Distribution
  • Radiopharmaceuticals
  • Radionuclide Imaging
  • Organ Specificity
  • Nuclear Medicine & Medical Imaging
  • Neuroblastoma
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Metabolic Clearance Rate
 

Citation

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Vaidyanathan, G., Welsh, P. C., Vitorello, K. C., Snyder, S., Friedman, H. S., & Zalutsky, M. R. (2004). A 4-methyl-substituted meta-iodobenzylguanidine analogue with prolonged retention in human neuroblastoma cells. Eur J Nucl Med Mol Imaging, 31(10), 1362–1370. https://doi.org/10.1007/s00259-004-1596-8
Vaidyanathan, Ganesan, Philip C. Welsh, Katia C. Vitorello, Stacey Snyder, Henry S. Friedman, and Michael R. Zalutsky. “A 4-methyl-substituted meta-iodobenzylguanidine analogue with prolonged retention in human neuroblastoma cells.Eur J Nucl Med Mol Imaging 31, no. 10 (October 2004): 1362–70. https://doi.org/10.1007/s00259-004-1596-8.
Vaidyanathan G, Welsh PC, Vitorello KC, Snyder S, Friedman HS, Zalutsky MR. A 4-methyl-substituted meta-iodobenzylguanidine analogue with prolonged retention in human neuroblastoma cells. Eur J Nucl Med Mol Imaging. 2004 Oct;31(10):1362–70.
Vaidyanathan, Ganesan, et al. “A 4-methyl-substituted meta-iodobenzylguanidine analogue with prolonged retention in human neuroblastoma cells.Eur J Nucl Med Mol Imaging, vol. 31, no. 10, Oct. 2004, pp. 1362–70. Pubmed, doi:10.1007/s00259-004-1596-8.
Vaidyanathan G, Welsh PC, Vitorello KC, Snyder S, Friedman HS, Zalutsky MR. A 4-methyl-substituted meta-iodobenzylguanidine analogue with prolonged retention in human neuroblastoma cells. Eur J Nucl Med Mol Imaging. 2004 Oct;31(10):1362–1370.
Journal cover image

Published In

Eur J Nucl Med Mol Imaging

DOI

ISSN

1619-7070

Publication Date

October 2004

Volume

31

Issue

10

Start / End Page

1362 / 1370

Location

Germany

Related Subject Headings

  • Tissue Distribution
  • Radiopharmaceuticals
  • Radionuclide Imaging
  • Organ Specificity
  • Nuclear Medicine & Medical Imaging
  • Neuroblastoma
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Metabolic Clearance Rate