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MIBG inhibits respiration: potential for radio- and hyperthermic sensitization.

Publication ,  Journal Article
Biaglow, JE; Manevich, Y; Leeper, D; Chance, B; Dewhirst, MW; Jenkins, WT; Tuttle, SW; Wroblewski, K; Glickson, JD; Stevens, C; Evans, SM
Published in: Int J Radiat Oncol Biol Phys
November 1, 1998

INTRODUCTION: Meta-iodobenzylguanidine (MIBG) in its 131I-labeled form is clinically used as a tumor-targeted radiopharmaceutical in the diagnosis and treatment of adrenergic tumors. This well established drug may have additional clinical applications as a radiosensitizer or hyperthermic agent, ie., MIBG reportedly inhibits mitochondrial respiration in vitro. The mechanism for MIBG inhibition of cellular oxygen consumption is uncertain. Moreover, MIBG reportedly stimulates glycolysis both in vitro and in vivo. Our studies show the effect of MIBG on 9L glioma oxygen consumption and redox status with tumors cells in vitro and in vivo. MATERIALS AND METHODS: The effects on electron transfer were determined by following oxygen consumption with a Clark oxygen electrode. Fluorescence measurements were used to determine effects of MIBG on intracellular electron acceptors, NADPH and flavoproteins, in vitro and in vivo. 31P-NMR was used to determine alterations in tumor cell pH in vivo. RESULTS: Our results show the inhibition of oxygen utilization with MIBG for cell suspensions in vitro. The same results were demonstrated for tumor cell suspensions rapidly isolated from tumors grown in rats. Moreover, NAD(P)H and flavoprotein (Fp) fluorescence changes were observed to rapidly occur following MIBG addition in vitro. Changes in intracellular pH measured with 31P-NMR, in vivo, precede the changes in fluorescence of NAD(P)H and Fp obtained with frozen sections of tumor. CONCLUSIONS: We conclude that 31P-NMR measurements and fluorescence changes, following MIBG injection, can be used as criterion for selecting the proper time to treat tumors with ionizing radiation or hyperthermia.

Duke Scholars

Published In

Int J Radiat Oncol Biol Phys

DOI

ISSN

0360-3016

Publication Date

November 1, 1998

Volume

42

Issue

4

Start / End Page

871 / 876

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Spectrometry, Fluorescence
  • Rats
  • Radiopharmaceuticals
  • Phosphorus
  • Oxygen Consumption
  • Oxidation-Reduction
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • NADP
 

Citation

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Biaglow, J. E., Manevich, Y., Leeper, D., Chance, B., Dewhirst, M. W., Jenkins, W. T., … Evans, S. M. (1998). MIBG inhibits respiration: potential for radio- and hyperthermic sensitization. Int J Radiat Oncol Biol Phys, 42(4), 871–876. https://doi.org/10.1016/s0360-3016(98)00334-4
Biaglow, J. E., Y. Manevich, D. Leeper, B. Chance, M. W. Dewhirst, W. T. Jenkins, S. W. Tuttle, et al. “MIBG inhibits respiration: potential for radio- and hyperthermic sensitization.Int J Radiat Oncol Biol Phys 42, no. 4 (November 1, 1998): 871–76. https://doi.org/10.1016/s0360-3016(98)00334-4.
Biaglow JE, Manevich Y, Leeper D, Chance B, Dewhirst MW, Jenkins WT, et al. MIBG inhibits respiration: potential for radio- and hyperthermic sensitization. Int J Radiat Oncol Biol Phys. 1998 Nov 1;42(4):871–6.
Biaglow, J. E., et al. “MIBG inhibits respiration: potential for radio- and hyperthermic sensitization.Int J Radiat Oncol Biol Phys, vol. 42, no. 4, Nov. 1998, pp. 871–76. Pubmed, doi:10.1016/s0360-3016(98)00334-4.
Biaglow JE, Manevich Y, Leeper D, Chance B, Dewhirst MW, Jenkins WT, Tuttle SW, Wroblewski K, Glickson JD, Stevens C, Evans SM. MIBG inhibits respiration: potential for radio- and hyperthermic sensitization. Int J Radiat Oncol Biol Phys. 1998 Nov 1;42(4):871–876.
Journal cover image

Published In

Int J Radiat Oncol Biol Phys

DOI

ISSN

0360-3016

Publication Date

November 1, 1998

Volume

42

Issue

4

Start / End Page

871 / 876

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Spectrometry, Fluorescence
  • Rats
  • Radiopharmaceuticals
  • Phosphorus
  • Oxygen Consumption
  • Oxidation-Reduction
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • NADP