omation mbers - Society for Laboratory Automation and Screening

TP049
Darren Hillegonds
Lawrence Livermore National Laboratory
Center for Accelerator Mass Spectrometry
7000 East Avenue, L-397
Livermore, California 94551
hillegonds1@llnl.gov
Co-Author(s)
John S. Vogel, Lawrence Livermore National Laboratory
David Herold and Robert Fitzgerald, Veterans Affairs San
Diego Healthcare System/University of California, San Diego
High Throughput Measurement of 41 Ca by Accelerator Mass Spectrometry to Quantitate
Small Changes in Individual Human Bone Turnover Rates
Biochemical bone turnover markers suffer from large analytical and natural fluctuations (20 – 30%), making small
differences in bone resorption impossible to resolve. This limits the clinical utility of such markers for individuals with
the skeletal complications associated with many disease states (e.g., metastatic cancer, renal failure, osteoporosis).
We are developing the capability to measure small changes (5 – 10%) in bone turnover rate in vivo by tagging the
living skeleton with 41 Ca. This measurement will enable earlier diagnosis of pathological processes and interactive
intervention with therapeutic agents, allowing modulation of a therapeutic agent to obtain the best individual result
for a patient. Among the stable and radioactive calcium isotopes, only 41 Ca is useful for direct quantitation of bone
turnover because it is extremely rare in nature and radiologically benign (105,000 y half-life, pure electron capture
decay). In support of several ongoing research projects, we have simplified and streamlined the sample preparation
methodology. This, combined with the highly automated analytical instrumentation, allows a single operator to
prepare or run more than 100 samples per day – significantly more than other 41 Ca programs worldwide. We have
also prepared new 41 Ca dose materials for oral and intravenous administration. This 41 Ca was provided from a
1% 41 Ca solution used in preparation of our primary standard, laboriously purified through selective precipitation
and ion exchange. Radiological purity was measured for both beta and gamma radiation – both were at typical
background levels. The trace elemental content was also measured, assuring the overall purity of the dose material
for human use.
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