Imaging of fluorine and boron from fluorinated boronophenylalanine in the same cell at organelle resolution by correlative ion microscopy and confocal laser scanning microscopy

Subhash Chandra, George Kabalka, Daniel R. Lorey, Duane R. Smith, Jeffrey A. Coderre

Research output: Contribution to journalArticle

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Abstract

Purpose: There is a clear need for a technique that provides subcellular locations of fluorine and boron atoms from fluorinated neutron capture agents because positron emission tomography is being tested as a tool for providing tumor boron concentrations in boron neutron capture therapy. Experimental Design: Ion microscopy was used in combination with confocal laser scanning microscopy to investigate the subcellular locations of fluorine and boron from fluorinated p-boronophenylalanine (F-BPA) in human glioblastoma T98G cells. The fluorinated compound was also compared with p-boronophenylalanine (BPA) for delivery of boron after a clinically relevant 6-h exposure. Mitochondria were identified by rhodamine 123 labeling. A strict cryogenic sample preparation was used, and measurements were made in fractured freeze-dried cells. Results: The nucleus, a perinuclear mitochondria-rich cytoplasmic region, and the remaining cytoplasm were the three subcellular regions identified in individual T98G cells. In cells treated with F-BPA, the mitochondria-rich perinuclear cytoplasmic region exhibited significantly lower fluorine and boron signals than the remaining cytoplasm and the nuclei. Ion microscopy observations revealed a nearly 1:1 distribution of fluorine and boron in subcellular compartments. Quantitative subcellular observations indicated that there was no significant difference in boron delivery to subcellular compartments between the F-BPA and nonfluorinated BPA. Conclusions: These observations provide the first direct evidence that fluorine and boron from fluorinated BPA are cocompartmentalized in cells and that the fluorinated compound is as efficient for boron delivery as the nonfluorinated BPA at a clinically relevant time point. These observations provide strong support for the use of F-BPA in positron emission tomography biodistribution studies for boron neutron capture therapy.

Original languageEnglish (US)
Pages (from-to)2675-2683
Number of pages9
JournalClinical Cancer Research
Volume8
Issue number8
StatePublished - Jan 1 2002
Externally publishedYes

Fingerprint

Boron
Fluorine
Confocal Microscopy
Organelles
Microscopy
Ions
Boron Neutron Capture Therapy
Mitochondria
Positron-Emission Tomography
Cytoplasm
Rhodamine 123
4-boronophenylalanine
Neutrons
Glioblastoma
Research Design

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Imaging of fluorine and boron from fluorinated boronophenylalanine in the same cell at organelle resolution by correlative ion microscopy and confocal laser scanning microscopy. / Chandra, Subhash; Kabalka, George; Lorey, Daniel R.; Smith, Duane R.; Coderre, Jeffrey A.

In: Clinical Cancer Research, Vol. 8, No. 8, 01.01.2002, p. 2675-2683.

Research output: Contribution to journalArticle

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abstract = "Purpose: There is a clear need for a technique that provides subcellular locations of fluorine and boron atoms from fluorinated neutron capture agents because positron emission tomography is being tested as a tool for providing tumor boron concentrations in boron neutron capture therapy. Experimental Design: Ion microscopy was used in combination with confocal laser scanning microscopy to investigate the subcellular locations of fluorine and boron from fluorinated p-boronophenylalanine (F-BPA) in human glioblastoma T98G cells. The fluorinated compound was also compared with p-boronophenylalanine (BPA) for delivery of boron after a clinically relevant 6-h exposure. Mitochondria were identified by rhodamine 123 labeling. A strict cryogenic sample preparation was used, and measurements were made in fractured freeze-dried cells. Results: The nucleus, a perinuclear mitochondria-rich cytoplasmic region, and the remaining cytoplasm were the three subcellular regions identified in individual T98G cells. In cells treated with F-BPA, the mitochondria-rich perinuclear cytoplasmic region exhibited significantly lower fluorine and boron signals than the remaining cytoplasm and the nuclei. Ion microscopy observations revealed a nearly 1:1 distribution of fluorine and boron in subcellular compartments. Quantitative subcellular observations indicated that there was no significant difference in boron delivery to subcellular compartments between the F-BPA and nonfluorinated BPA. Conclusions: These observations provide the first direct evidence that fluorine and boron from fluorinated BPA are cocompartmentalized in cells and that the fluorinated compound is as efficient for boron delivery as the nonfluorinated BPA at a clinically relevant time point. These observations provide strong support for the use of F-BPA in positron emission tomography biodistribution studies for boron neutron capture therapy.",
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