Biological accelerator mass spectrometry at Uppsala University

Salehpour, Mehran; Possnert, Göran; Bryhni, Helge; Palminger-Hallén, Ira; Ståhle, Lars

doi:10.1016/j.apradiso.2008.08.001

Cited by 11 publications

(14 citation statements)

References 7 publications

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“…The amount of the contamination, depending on the system, is typically between 1 and 10 mg C per sample depending on the specific laboratory contamination level, routines, etc. Secondly, small samples produce lower secondary ion currents than standard samples, 16 and this affects the measurement precision detrimentally. One of the parameters in an AMS experiment that is often optimized is the ion current produced by the sample.…”

Section: Resultsmentioning

confidence: 99%

“…It can be seen that for large samples above a few hundred mg of carbon the current is constant at about 1000 nA which is typical for a standard sample in our laboratory. Data for large samples in the 1-10 mg range is not presented as it is well established that large samples have stable current output, independent of sample mass (see, e.g., 16 ). As the sample size is reduced, the current decreases.…”

Section: Resultsmentioning

confidence: 99%

“…In our laboratory we are well below this value. 16 We have consequently prepared a number of samples with different amounts of DNA which have been added to the carbon carrier, TRB, ensuring that the same amount is used (1.56 AE 0.05 mg) for all samples. After the carrier addition, the samples have been prepared according to method 1 or 2 and measured by AMS.…”

Section: Resultsmentioning

confidence: 99%

“…It is known that by reducing the mass of the carrier the isotopic ratio is increased (e.g. see Salehpour et al 16 ). Another point which should be noted is that we have not measured the carbon content of the hydrated DNA sample.…”

Section: Resultsmentioning

confidence: 99%

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Accelerator mass spectrometry of small biological samples

Salehpour

Forsgard

Possnert

2008

Rapid Comm Mass Spectrometry

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Accelerator mass spectrometry (AMS) is an ultra-sensitive technique for isotopic ratio measurements. In the biomedical field, AMS can be used to measure femtomolar concentrations of labeled drugs in body fluids, with direct applications in early drug development such as Microdosing. Likewise, the regenerative properties of cells which are of fundamental significance in stem-cell research can be determined with an accuracy of a few years by AMS analysis of human DNA. However, AMS nominally requires about 1 mg of carbon per sample which is not always available when dealing with specific body substances such as localized, organ-specific DNA samples. Consequently, it is of analytical interest to develop methods for the routine analysis of small samples in the range of a few tens of mg. We have used a 5 MV Pelletron tandem accelerator to study small biological samples using AMS. Different methods are presented and compared. A 12 C-carrier sample preparation method is described which is potentially more sensitive and less susceptible to contamination than the standard procedures.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Accelerator mass spectrometry of small biological samples

Salehpour

Forsgard

Possnert

2008

Rapid Comm Mass Spectrometry

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“…The sample preparation was performed as described previously. [9][10][11] Briefly, the samples collected from the animal study were lyophilized (Scanvac Modulespin 40, Scanlaf A/S, Denmark) for 2 h at 2000 rpm at 10 -3 mbar vacuum and were subsequently placed in quartz tubes C for 3 h to produce CO 2 gas. The gas was cryogenically transferred in vacuum to vials containing 80 mg zinc powder as reducing agent + 2 mg iron powder as catalyst.…”

Section: Ams Sample Preparationmentioning

confidence: 99%

Application of accelerator mass spectrometry to macromolecules: preclinical pharmacokinetic studies on a polybisphosphonate

Salehpour

Håkansson

Höglund³

et al. 2011

Rapid Comm Mass Spectrometry

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Data on the use of accelerator mass spectrometry (AMS) in conjunction with in vivo studies of macromolecular drugs are scarce. The present study shows the versatility of this technique when investigating the pharmacokinetics (PK) of a macromolecular drug candidate, a polybisphosphonate conjugate (ODX). The aforementioned is a polymer (molecular weight ~30 kDa) constituting a carbohydrate backbone with covalently linked ligands (aldendronate and aminoguanidine) and is intended for treatment of osteoporosis and the therapy of bone metastasis from prostate cancer. The conjugate is prepared through partial oxidation of the carbohydrate and sequential coupling of the ligands by reductive amination. (14)C was incorporated in the conjugate by means of coupling a commercially available (14)C-lysine in the conjugation sequence. Fifteen rats were injected intravenously with (14)C-labelled ODX (150 µg, 14 Bq/rat) and blood samples were collected at 1, 2, 4, 6, and 24 h post-injection (3 rats/time point). Liver, spleen and kidney samples were collected at 4 and 24 h post-injection. Blood from each time point (triplicate) were collected for AMS measurement determining the isotopic ratio ((14)C/(12)C) and consequently the drug concentration in blood. ODX showed a transient presence in blood circulation; 93% of the total dose was cleared from the circulation within 1 h. The half-life after 1 h was estimated to be about 3 h; 0.7% of the administered (14)C dose of ODX remained in circulation after 24 h. The major (14)C accumulation was in the liver, the spleen and the kidneys indicating the probable route of metabolism and excretion. This study demonstrates the versatility of AMS for pharmacological in vivo studies of macromolecules. Labelling with (14)C is relatively simple, inexpensive and the method requires minimal radioactivity, eliminating the need for radioprotection precautions in contrast to methods using scintillation counting.

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Current literature in mass spectrometry

2009

J. Mass Spectrom.

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Biological accelerator mass spectrometry at Uppsala University

Cited by 11 publications

References 7 publications

Accelerator mass spectrometry of small biological samples

Accelerator mass spectrometry of small biological samples

Application of accelerator mass spectrometry to macromolecules: preclinical pharmacokinetic studies on a polybisphosphonate

Current literature in mass spectrometry

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