A
collaboration between scientists at UCLA, Caltech,
Stanford, Siemens and Fluidigm have developed a new
technology using integrated microfluidics chips for
simplifying, lowering the cost and diversifying the
types of molecules used to image the biology of disease
with the medical imaging technology, Positron Emission
Tomography (PET). These molecules are used with PET
to diagnostically search throughout the body to look
for (image) the molecular errors of disease and to
guide the development of new molecular therapeutics.
PET is a new generation of medical imaging for examining
the biology of disease that has been shown to dramatically
improve the detection of cancer, stage the extent
of cancer throughout the body, detect recurrence
of cancer and to help select the right therapy for
individual patients.
In Alzheimer's disease, PET has been shown to have
a 93% accuracy in detecting Alzheimer's about three
years before the conventional diagnosis of "Probable
Alzheimer's", when integrated into the clinical workup
of patients. In addition, PET has been shown to detect
Alzheimer's and other neurological disease years
before even symptoms are expressed. PET is also employed
to determine which patients with cardiovascular disease
will benefit from bypass surgery and angioplasty.
These and other clinical uses of PET employ a labeled
version of the sugar glucose, called Fluorodeoxyglucose
(FDG). Glucose is a critical fuel for cells throughout
the body to perform their normal functions. For example,
95% of the energy for the brain to function comes
from glucose. In addition, cancer cells increase
their metabolism of glucose about 25 fold. There
were about three million clinical PET studies performed
in clinical services throughout the world in 2005.
Published this week in the journal Science, scientists
demonstrated a new technology of a programmable chip
that can dramatically accelerate the development
of many new molecular imaging molecules for PET.
As a proof of principle, this group of academic and
commercial scientists demonstrated that FDG could
be synthesized on a "stamp-size" chip. These chips
have a design similar to integrated electronic circuits,
except they are made up of fluid channels, chambers
and values (switches) that can carry out many chemical
operations to synthesize and label molecules for
PET imaging. All the operations of the chip are controlled
and executed by a PC.
FDG was produced on the chip and used to image glucose
metabolism in a mouse with a specially designed PET
scanner for mice produced by Siemens, called a microPET.
The Science paper also illustrated that this technology
can also produce the amount of FDG required for human
studies. More importantly, the paper illustrates
a new base technology for producing and delivering
a diverse array of molecular imaging molecules and
labeled drugs for use with PET to examine the biology
of many diseases for molecular diagnostics and to
guide the development of new molecular therapeutics
(drugs).
"Chemists synthesize molecules in a lab by mixing
chemicals in beakers and repeating experiments many
times, but one day soon they'll sit at a PC and carry
out chemical synthesis with the digital control,
speed and flexibility of today's world of electronics
using a tiny integrated microfluidic chip," said
Hsian-Rong Tseng, Ph.D, assistant professor of molecular
and medical pharmacology, Crump Institute for Molecular
Imaging, David Geffen School of Medicine at UCLA.
There is a vast distribution of manufacturing sites
throughout the world producing PET molecular imaging
molecules for hospitals, universities and pharmaceutical
companies. The goal is to integrate these new chips
into a small control device operated by a PC that
will be commercially produced. Then to ship chips
to users so they can produce whatever molecules they
choose for molecular imaging with PET. These chips
will be an enabling technology to fuel growth in
the number and diversity of imaging molecules and
applications of PET in biology and pharmaceutical
research and in the care of patients.
The research is supported by a Department of Energy
grant to the UCLA Institute for Molecular Medicine,
the National Cancer Institute, the Norton Simon Research
Foundation, the UCLA National Cancer Institute Molecular
Imaging Training grant and commercial support from
Siemens and Fluidigm.
The authors and participating institutions and companies
include:
David Geffen School of Medicine at UCLA:
Hsian-Rong Tseng, Guodong Sui, Chengyi Jenny Shu, Alek N. Dooley, Owen N.
Witte, Nagichettiar Satyamurthy, David Stout, Michael Phelps
Caltech:
James R. Heath (also with UCLA), Chung-Cheng Lee, Young-Shik Shin, Arkadij
Elizarov
Stanford:
Stephen Quake
Siemens Biomarker Solutions:
Hartmuth Kolb (also with the David Geffen School of Medicine at UCLA)
Fluidigm:
Jiang Huang, Antoine Davidon, Paul Wyatt
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