Is 99Tcm hexamethyl-propyleneamine oxime uptake in the tissues related to glutathione cellular content?

Am, el-Shirbiny; Sadek, Samy; Owunwanne, Azu; Yacoub, T; Hm, Abdel-Dayem

doi:10.1097/00006231-198912000-00007

Cited by 14 publications

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“…The theory that HMPAO reacts with intracellular GSH 3,4 " o,11 has been questioned by some authors, who did not find a relationship between biodistribution of HMPAO and tissue GSH content in animals partially depleted of GSH. 21 However, as postulated recently by Sasaki et al 22 the high specific activity of HMPAO and its rapid rate of reaction with GSH may allow even low levels of GSH to trap HMPAO quantitatively; if this is correct, accumulation of HMPAO may be independent of cell type and species, as seen in the present results. Other authors have recently suggested that HMPAO retention is dependent upon the balance between intracellular and extracellular redox state.'…”

Section: Discussionsupporting

confidence: 73%

Accumulation of99mTc-HMPAO and99mTc-ECD in rodent and human breast tumor cell linesin vitro

et al. 1997

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The accumulation of 99mTc-HMPAO and 99mTc-ECD was studied in rat (MatB) and human (MCF-7) breast tumor cell lines in vitro as a function of incubation time. The general pattern was the same for both tracers and both cell lines: the tracer rapidly and extensively accumulated in the cells but a plateau was reached in 15-30 minutes. Accumulation of HMPAO was higher than that of ECD, did not show a difference between rat and human cells, and correction of HMPAO data for intracellular sequestration and extracellular metabolism resulted in a linear increase in accumulation with time. In contrast, accumulation of ECD was approximately 2-fold higher in human cells than in rat cells but after correction for sequestration and metabolism a plateau remained. These experiments show differences between HMPAO and ECD in their accumulation and retention in breast cancer cells in vitro and support that the need for further work on the potential clinical role for HMPAO in tumor characterization.

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Section: Discussionsupporting

confidence: 73%

Accumulation of99mTc-HMPAO and99mTc-ECD in rodent and human breast tumor cell linesin vitro

et al. 1997

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“…Such discrepancies also have been reported in vivo. DEM-treated mice and rats showed only a very small decrease in brain 99m Tc-d,l-HMPAO retention as compared with controls, despite significant decrease in glutathione content (El-Shirbiny et al, 1989;Sasaki et al, 1996). Moreover, BSO-treated mice did not display a substantial reduction in 99m Tc-d,l-HMPAO retention, whereas glutathione levels were significantly reduced (Sasaki and Senda, 1997).…”

Section: S Zerarka Et Al 464mentioning

confidence: 99%

Astrocytes as a Predominant Cellular Site of ^99mTc-HMPAO Retention

Zerarka

Pellerin

Slosman

et al. 2001

J Cereb Blood Flow Metab

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Technetium-99m-d,l-hexamethylpropylene amine oxime ((99m)Tc-HMPAO) retention in the brain monitored by single photon emission computed tomography (SPECT) is currently used as a marker of cerebral blood flow. The purported mechanism by which (99m)Tc-HMPAO accumulates in the brain is through its intracellular conversion from a lipophilic form to more hydrophilic derivatives within the brain parenchyma. The issue of the contribution of different cell types on (99m)Tc-HMPAO retention was investigated in vitro by studying the accumulation of (99m)Tc-HMPAO in primary cultures of mouse cortical astrocytes and neurons. Results show that (99m)Tc-HMPAO retention predominates in astrocytes over neurons by a factor of approximately 2.5 (0.26 +/- 0.05 vs. 0.095 +/- 0.042 fmol/mg protein after 120 minutes, respectively). Diethyl maleate (60 micromol/L), ethacrynic acid (1 mmol/L) and buthionine sulfoximine (1 mmol/L), 3 agents which significantly reduced glutathione levels also decreased (99m)Tc-HMPAO retention in both astrocytes (29%, 3%, and 46% of control, respectively) and neurons (69%, 11% and 63% of control). Decrease did not always correlate with glutathione levels, however, which suggests that other factors could be involved. The possibility that cell energy status determines (99m)Tc-HMPAO retention was also assessed. Agents that activate (glutamate, azide) or inhibit (cytochalasin B) glucose utilization in astrocytes, as measured by the (3)H-2-deoxyglucose method, were without effect on (99m)Tc-HMPAO retention. In conclusion, the data presented indicate that astrocytes may constitute a prominent site of (99m)Tc-HMPAO retention and most likely contribute significantly to the SPECT signal. In addition, the data also suggest that specific alterations in glial cell metabolism could explain flow-independent changes in (99m)Tc-HMPAO retention in the brain as observed by SPECT in some pathologies.

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Design of radiopharmaceuticals

Owunwanne

Patel

Sadek

1995

The Handbook of Radiopharmaceuticals

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Is 99Tcm hexamethyl-propyleneamine oxime uptake in the tissues related to glutathione cellular content?

Cited by 14 publications

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Accumulation of99mTc-HMPAO and99mTc-ECD in rodent and human breast tumor cell linesin vitro

Accumulation of99mTc-HMPAO and99mTc-ECD in rodent and human breast tumor cell linesin vitro

Astrocytes as a Predominant Cellular Site of ^99mTc-HMPAO Retention

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Is 99Tcm hexamethyl-propyleneamine oxime uptake in the tissues related to glutathione cellular content?

Cited by 14 publications

References 0 publications

Accumulation of99mTc-HMPAO and99mTc-ECD in rodent and human breast tumor cell linesin vitro

Accumulation of99mTc-HMPAO and99mTc-ECD in rodent and human breast tumor cell linesin vitro

Astrocytes as a Predominant Cellular Site of 99mTc-HMPAO Retention

Design of radiopharmaceuticals

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Astrocytes as a Predominant Cellular Site of ^99mTc-HMPAO Retention