A simple method for the quantitation of 14C-whole-body autoradiograms

doi:10.1016/0883-2889(87)90019-0

International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes

Volume 38, Issue 5, 1987, Pages 329-333

https://doi.org/10.1016/0883-2889(87)90019-0 Get rights and content

Abstract

A simple method for the quantitation of ¹⁴C-whole-body autoradiograms by comparative densitometry is described. If processed under the same conditions as the samples of tissues to be investigated, a radioactive blood scale can be used as standard, with the exception of samples from bones, eyes and fat. This method is demonstrated to be simple, accurate, reproducible and precise.

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Application of whole-body autoradiography in toxicology
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Accumulation and retention of mercury in the mouse
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J.M. Bland et al.
Statistical methods for assessing agreement between two methods of clinical measurement
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Factors affecting the sensitivity of X-ray films used for whole-body autoradiography
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Standardization and calibration of whole-body autoradiography for routine semi-quantitative analysis of the distribution of ¹⁴C-labeled compounds in animal tissues
Toxicol. Appl. Pharmacol.
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Quantification in macroscopic autoradiography with Carbon-14. An evaluation of the method
Int. J. Appl. Radiat. Isot.
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H. Kutzim
Die quantitative Bestimmung der Verteilung von S³⁵-Sulfat bei der Maus mittels Autoradiographie
Nuklearmedizin
(1963)

There are more references available in the full text version of this article.

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Simple methodology for ensuring the precision of measuring radioactivity at low concentrations in very small tissues using quantitative whole-body autoradiography
2021, Regulatory Toxicology and Pharmacology
Citation Excerpt :
When sliced, the standards are placed along the whole-body of rat, and a calibration curve is prepared for each section to ensure not only the quantitative value but also the section thickness. In QWBA, the effect of self-absorption, which differs in respective tissue, interferes with quantification (Schweitzer et al., 1987). Blood with moderate self-absorption in each tissue is suitable as a standard and widely used, but its self-absorption is similar to that of the liver (Inazawa et al., 2004).
Quantitative whole-body autoradiography (QWBA) is largely used to evaluate tissue distribution of small molecule drugs. In QWBA, radioactivity is measured as the intensity obtained from the autoradiogram. It is known that lower intensity per a region of interest (ROI) or smaller size of ROI increases the variability of intensity. In fact, as some tissues are very small (e.g., the choroidea), ensuring reliability on the intensity for measuring radioactivity in these tissues is difficult in case of under- or over-estimation of radioactivity concentration owing to their variation of low radioactivity intensity of ROI. We thus analyzed the relationships between the size, intensity, and precision of ROI to determine the statistically significant lower limit of quantification (LLOQ) in very small tissues. To investigate the difference in correlation between the radiation source (commercial planar radiation standard [com-ST] and self-made radiation standard [self-ST] consisting of radioactive compounds and matrices), apparatus, or setting environment of the apparatus, correlation analysis was conducted under various conditions. Our results revealed that LLOQ can be calculated by simply using the correlation equation because a common relationship was observed between self-ST, which is used in QWBA, and com-ST. This methodology was thus considered valuable for ensuring LLOQ determination in QWBA.
High-resolution beta imaging
2020, Handbook of Radioactivity Analysis: Volume 2: Radioanalytical Applications
Since the discovery by Henri Becquerel at the beginning of the last century that “mysterious” radiation coming from uranium impressed photographic plates, autoradiography has been at the center of radionuclide measurements both in the physical and biological sciences. Original autoradiography, involving the photographic processes based on the direct application of samples against a photographic emulsion, remains, even today, one of the best techniques for optimal spatial resolution. However, its lack of sensitivity and poor linearity response leaves little space between under- and overexposure and usually requires long exposure times for low-energy isotopes. Hence new approaches to autoradiography, based on photoluminescence of phosphor storage screens and digital autoradioluminography, have been developed to address time and quantification constraints. This chapter aims to describe these state-of-the-art technologies and give examples of their applications in the biomedical sciences.
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2012, Handbook of Radioactivity Analysis
Age dependent incorporation of 14C-DHA into rat brain and body tissues after dosing various 14C-DHA-esters
2010, Prostaglandins Leukotrienes and Essential Fatty Acids
The omega-3 fatty acid docosahexaenoic acid (DHA) accounts for 10% of fatty acids in human brain and is critical for neuronal function and brain development. Mechanisms of transport, accumulation and conservation of DHA in the brain are unclear. The objective of the study was to quantify the age dependent DHA incorporation into the brain of 2-, 4- or 10-week-old rats after a bolus dose of different DHA-esters.
Rats were gavaged with ¹⁴C-DHA-TAG, ¹⁴C-DHA-PL or ¹⁴C-DHA-TAG+PL at 2 mg DHA/kg BW. After 24 h the distribution of radioactivity in body and brain regions was determined using quantitative whole body autoradiography (QWBA). Radiolabeled compounds were extracted from the brains to determine the identity of the radiolabeled compounds.
Accumulation of orally ingested ¹⁴C-DHA in rat brain was less than 1% of the dose and decreased with age. Ester specific differences were seen only in 10-week-old rats, where oral ¹⁴C-DHA-PL delivered a 2-fold higher accretion of radioactivity in the brain.
Less than 1% of a dietary achievable DHA dose reached the rat brain within 24 h. Optimal efficacy of DHA-PL may occur in older age groups.
The distribution pattern of intravenous [14C] artesunate in rat tissues by quantitative whole-body autoradiography and tissue dissection techniques
2008, Journal of Pharmaceutical and Biomedical Analysis
Quantitative whole-body autoradiography (QWBA) and liquid scintillation counting (LSC) have been conducted to determine the metabolic profiles and tissue distribution of [¹⁴C] labeled artesunate (AS) injection in rats. The QWBA technique showed more accurate results in the quantification of radioactivity in 40 organs and tissues, compared to 19 organs with the LSC technique. The benefit of QWBA was especially apparent on measurements of bile, bone marrow, and gland organs; however, the LSC method produced more relevant findings than QWBA. Particularly, the LSC method allowed access to the following distribution patterns that were unavailable via QWBA performance: such as pharmacokinetic evaluation of radiolabeled AS in blood and plasma, tissue/plasma partition coefficients, conversion pathway of AS to dihydroartemisinin (DHA, an active and major metabolite of AS), unchanged AS and DHA in plasma, mass balance assessment, urinary and faecal eliminations, drug pathway with conjugation, [¹⁴C] AS binding with RBC and plasma protein, and metabolites identification. Even though the each method has its own advantages, common profiles were obtained from the two processes as shown in the results of the biliary metabolism, long-lasting metabolites, tissue distribution profiles, and multiple concentration peaks, which indicate a [¹⁴C] AS enterohepatic circulation.
Compound and metabolite distribution measured by MALDI mass spectrometric imaging in whole-body tissue sections
2007, International Journal of Mass Spectrometry
The determination of the compound distribution in laboratory animal tissue in early development is a standard process in pharmaceutical research. While this information is traditionally obtained by means of whole-body autoradiography using radiolabeled compounds, this technology does not distinguish between metabolites and parent compound. The technique described in this article, termed matrix-assisted laser desorption/ionization (MALDI) mass spectrometric imaging, can fill this gap by simultaneously measuring compound and multiple metabolites distributed in whole-body tissue sections, using non-labeled compounds.

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International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes

Abstract

References (14)

Application of whole-body autoradiography in toxicology

CRC

Accumulation and retention of mercury in the mouse

Arch. Environ. Health

Statistical methods for assessing agreement between two methods of clinical measurement

Lancet

Factors affecting the sensitivity of X-ray films used for whole-body autoradiography

Xenobiotica

Standardization and calibration of whole-body autoradiography for routine semi-quantitative analysis of the distribution of ¹⁴C-labeled compounds in animal tissues

Toxicol. Appl. Pharmacol.

Quantification in macroscopic autoradiography with Carbon-14. An evaluation of the method

Int. J. Appl. Radiat. Isot.

Die quantitative Bestimmung der Verteilung von S³⁵-Sulfat bei der Maus mittels Autoradiographie

Nuklearmedizin

Cited by (42)

Simple methodology for ensuring the precision of measuring radioactivity at low concentrations in very small tissues using quantitative whole-body autoradiography

High-resolution beta imaging

High-Resolution Beta Imaging

Age dependent incorporation of <sup>14</sup>C-DHA into rat brain and body tissues after dosing various <sup>14</sup>C-DHA-esters

The distribution pattern of intravenous [<sup>14</sup>C] artesunate in rat tissues by quantitative whole-body autoradiography and tissue dissection techniques

Compound and metabolite distribution measured by MALDI mass spectrometric imaging in whole-body tissue sections

A simple method for the quantitation of 14C-whole-body autoradiograms

Abstract

Application of whole-body autoradiography in toxicology

CRC

Accumulation and retention of mercury in the mouse

Arch. Environ. Health

Statistical methods for assessing agreement between two methods of clinical measurement

Lancet

Factors affecting the sensitivity of X-ray films used for whole-body autoradiography

Xenobiotica

Standardization and calibration of whole-body autoradiography for routine semi-quantitative analysis of the distribution of 14C-labeled compounds in animal tissues

Toxicol. Appl. Pharmacol.

Quantification in macroscopic autoradiography with Carbon-14. An evaluation of the method

Int. J. Appl. Radiat. Isot.

Die quantitative Bestimmung der Verteilung von S35-Sulfat bei der Maus mittels Autoradiographie

Nuklearmedizin

A simple method for the quantitation of ¹⁴C-whole-body autoradiograms

Standardization and calibration of whole-body autoradiography for routine semi-quantitative analysis of the distribution of ¹⁴C-labeled compounds in animal tissues

Die quantitative Bestimmung der Verteilung von S³⁵-Sulfat bei der Maus mittels Autoradiographie