A Publication Of Radlink Diagnostic Imaging (S) Pte Ltd

• Issue No: 01-2009 • Mica (P) No: 253/02/2009

gateway w w w. r a d l i n k . c o m . s g

Care • Comfor t • Connect

Message
from the MD

I
trust you have had a great start to the year. On behalf of RadLink Diagnostic Imaging (S) Pte Ltd and
its other subsidiaries, I would like to thank you for your support.
RadLink is moving forward, stronger than ever as a comprehensive service provider for your
diagnostic imaging needs. We are at your service from a pre-employment chest X-ray to the diagnosis
and staging of cancer with a PET/CT scan.

Our latest achievement is the successful installation and commissioning of a state-of-the-art-cyclotron

that will produce advanced radiopharmaceuticals beyond fluoro-2-deoxy-D-glucose (or “FDG” as
commonly known). FDG is the most common radiopharmaceutical used in a PET/CT scan. Our cyclotron
was officially inaugurated by Prof Sir George Radda from A*Star on 5th March 2009.
In this issue of RadLink News you will find articles on exciting developments that improve the quality
of patient care and provide industry trends and updates on diagnostic radiology.
We look forward to your continued support in 2009.

Chan Wai Chuen

Managing Director

In this Issue
2 New Facility 3 Industry News 6 New Doctors
Making History: Our Cyclotron PET Scores Big Win in United States Dr Maung Maung Saw
Facility
4-5 Focus 7 New Technology
Radiopharmaceuticals: A Primer What is Time-of-Flight PET/CT?

6 Image of the Month 8 The Back Page

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 New Facility
Making History:
Our Cyclotron Facility
the development and translation of biomedical research
discoveries into clinical applications.”
Singapore Radiopharmaceutical’s 434 square meter
facility consists of a 16.5 MeV GE PETtrace cyclotron
and a central radiopharmacy. It has two synthesis
clean rooms with automatic synthesis modules for
the production of 18F-FDG and other advanced PET
radiopharmaceuticals. Stringent quality control is
accomplished by advance analytical instruments
such as radio-HPLC (High performance liquid
chromatography), gas chromatography, GC-MS (mass
spectrometry) and gamma spectroscopy. These are
supported by a chemistry laboratory, clean rooms for
sterile preparation and assembly of raw materials.
Professor Sir George Radda, Guest-of-Honour addressing the audience. Singapore Radiopharmaceuticals has begun sup-
plying 18F-FDG radiopharmaceutical to our PET/CT

S
INGAPORE Radiopharmaceuticals Pte Ltd has centre; Singapore PET and Cardiac Imaging Centre Pte
established a $10.8 million state-of-the-art Ltd from 30th March 2009. Besides 18F-FDG, other
cyclotron and central radiopharmacy at Singapore radiopharmaceuticals coming up from the facility in
Science Park II for the production of advanced positron-
emission tomography (PET) radiopharmaceuticals for
molecular imaging of cancer, heart and brain diseases
and biomedical research.
This facility was officially inaugurated by Prof
Sir George Radda (CBE, FRS), Chairman, Singapore
Bioimaging Consortium, (A*Star) on 5th March 2009.
“The value of our investment and the scale of its
capabilities signal our commitment to produce advan-
ced radiopharmaceuticals, not presently available in
the region, for cutting edge molecular imaging, diag-
nosis, monitoring and research of cancer, heart and brain
diseases,” said Mr Chan Wai Chuen, Managing Director
of RadLink Diagnostic Imaging (S) Pte Ltd. “Singapore
Radiopharmaceuticals Pte Ltd will enhance Singapore’s Dr Maung Maung Saw showing Professor Sir George Radda around the
cyclotron facility.
strong international reputation by expanding the range
of medical diagnostic and treatment options.”
“We welcome Singapore Radiopharmaceutical’s the coming months include C-11 Choline for prostate
facility which supports our mission to foster closer cancer, C-11 Acetate for liver cancer, 18F-MISO for
collaboration in bioimaging amongst researchers and hypoxia imaging and 18F-FLT as a proliferation tracer;
medical practitioners,” said Professor Sir George Radda i.e. as a non-invasive staging tool and a tool to monitor
(CBE, FRS). “The facility’s capabilities will support the the response to anticancer treatment.
growth of multi-disciplinary research activities and speed For more information, please go to www.radiopharmaceuticals.com.sg

2

PET Scores Big Win in United States, with CMS Coverage for 11 Cancers
T
HE Centers for Medicare &
Medicaid Services issued its long-
awaited decision late yesterday
for a national coverage determination
(NCD) to expand coverage for all
nine oncologic conditions under
consideration, along with two additional
cancers — ovarian and myeloma — to
allow initial PET diagnostic testing for
Medicare beneficiaries.
The agency has decided to adopt a
coverage framework that replaces the
four-part diagnosis, staging, restaging
and monitoring response to treatment
categories with a two-part framework
that differentiates FDG-PET imaging
used to inform the initial antitumor
treatment strategy from other uses
related to guiding subsequent antitumor
treatment strategies after the completion
of initial treatment.
This decision was based, in large part, on compelling
clinical evidence of the effectiveness of PET for cancer
management and treatment contained in the National
Oncologic PET Registry (NOPR), a comprehensive
study released in May 2008 in the Journal of Clinical
Oncology that showed a striking consistency of the
impact of PET on referring physicians’ intended
management plans in more than one in three patients.
This prompted the registry to formally ask CMS to
reconsider a national coverage determination (NCD)
on oncologic use of PET. NOPR was established in
2006 to track the utility of PET in patients with cancer.
The May 2008 study includes data from more than
41,000 patients. NOPR is sponsored by the Academy
of Molecular Imaging (AMI) and managed by the
American College of Radiology (ACR) and ACR Imaging
Network (ACRIN). The registry received input from —
and is endorsed by — ACR, the American Society for
Clinical Oncology (ASCO) and SNM.
Previously, PET scans for many cancers were
reimbursed only if the PET facility submitted data to
the NOPR. Now, all Medicare beneficiaries with certain
cancers will be covered by Medicare for at least one PET
scan. The nine currently covered cancers have all been
expanded to cover the subsequent treatment strategy,
in addition to initial diagnosis. For all other cancers, PET
coverage for subsequent treatment strategy evaluation
Industry News
requires participation in an approved
Coverage with Evidence Development
(CED) program, such as a modified
NOPR.
CMS has determined that “the
evidence is adequate to determine
that the results of FDG-PET imaging
are useful in determining the
appropriate initial treatment strategy
for beneficiaries with suspected
solid tumors and myeloma and
improve health outcomes and thus
are reasonable and necessary.”
Therefore, CMS will cover only one
FDG-PET study for beneficiaries who
have solid tumors that are biopsy
proven or strongly suspected based on
other diagnostic testing.
However, CMS has determined that
the available evidence is sufficient to
determine that FDG-PET imaging for
subsequent anti-tumor treatment strategy for tumor types
other than breast, colorectal, esophagus, head and neck
(non-CNS/thyroid), lymphoma, melanoma, non-small cell
lung, and thyroid may be covered as research through
coverage with evidence development (CED).
“This is a major victory for patients,” said Robert W.
Atcher, Ph.D., M.B.A., president of SNM and University
of New Mexico/Los Alamos National Laboratory professor
of pharmacy. “CMS’ decision to cover PET scans for
cancer demonstrates the intrinsic medical value of PET
and important role of these scans in diagnosing, staging,
restaging and monitoring treatment for many cancers.”
SNM applauded the CMS decision, saying it will save
patients thousands of dollars who would otherwise have
to pay out-of-pocket for their PET scans. Additionally,
this decision increases the likelihood that private insurers
will eventually follow CMS’ lead.
“For years, physicians and researchers around the
world have known that PET is an invaluable diagnostic
tool for guiding management of patients with a wide
range of cancers,” said Barry Siegel, M.D., co-chair
of the NOPR Working Group and chief of the nuclear
medicine at the Mallinckrodt Institute of Radiology,
St. Louis, Mo. “The evidence contained in the NOPR
study proves the effectiveness of PET as an essential
part of a cancer patient’s treatment planning.”
This article is reprinted from www.healthimaging.com
3
 Focus
A Brief Account on
Advanced PET
Radiopharmaceuticals
C
URRENTLY many imaging modalities are available, such as MRI, CT, X-ray, ultrasound, SPECT and PET.
Every modality has its own advantages and disadvantages, but only nuclear medicine techniques such
as SPECT and PET have truly molecular imaging capability. All of the nuclear medicine procedures
begin with administration of either radioisotope or radiopharmaceutical.
Although the number of molecular probes that can be labeled with positron emitting radioisotopes is large,
clinical practice has been limited principally to the use of a glucose analog, 18F-FDG. Cancer cells exhibit an
increased rate of glycolysis and 18F-FDG PET scan is able to assess a fundamental alteration in the cellular
metabolism of glucose that is common to all neoplasms. But there are some inherent limitations of 18F-FDG
PET that can result in false-negative and false-positive findings which are commonly associated with infection
or inflammation. Apart from that precise anatomic location can be difficult in certain anatomic region such
as head and neck, bladder region. Tumors with low metabolic rate (e.g. bronchoalveolar carcinoma) may
show minimal uptake and certain tumors are known to have poor avidity for 18F-FDG (prostate carcinoma
and hepatocellular carcinoma). 18F-FDG PET is also generally considered not to be useful in the assessment
of possible cerebral metastases from known primary neoplasms. These conditions are generally known as
“FDG Black Hole” areas.
The main aim of Singapore Radiopharmaceuticals Pte Ltd is to provide advanced radiopharmaceuticals
for the best diagnosis, treatment planning, response monitoring, therapy and prognosis. Not only in providing
the drug of the millennium “18F-FDG” but also in provision of “beyond FDG tracers”. Five examples of these
tracers are given below.

18F-FLT
The level of
proliferation is a
key parameter for
characterization of
neoplastic lesions.
The efficacy of
2- [18F] fluoro-L-
thymidine, commonly
known as FLT, has Comparison of (C) FDG
been tested in different types of carcinomas, scan, (D) 18F-FLT scan
such as Non-Hodgkin’s lymphoma, gastric in a patient with grade II
cancer, soft tissue sarcoma, melanoma, lung oligodentroglioma.
cancers, etc with good results3.

4
 11C-Acetate
11C-Acetate has been used to study
oxidative metabolism of the myocardium.
More recent studies have shown that
11C-Acetate is also accumulated by various
malignancies, including prostate cancer1
and hepatocellular carcinoma2.
Comparison of
(A) FDG scan,
(B) 11C-Acetate
scans in a patient
with hepatocellular
carcinoma.
18F-Fluoride
PET using 18F-Fluoride was
introduced in the 1990s to
quantify bone formation.
18F-Fluoride is taken up by
mineralizing bone in proportion
to osteoblastic activity. Using
dynamic acquisition, arterial
blood sampling, and kinetic modeling, PET fluoride has been used to study
normal and pathologic bone metabolism.
11C-Raclopride
11C-Raclopride has become one of the
most widely used neuro-receptor imaging
agents in PET in which striatal D2 tone is
of interest – for example, in Parkinson’s
disease, schizophrenia and substance
abuse5.
11C-
Raclopride
scan in a
patient with
Parkinson’s
disease.
18F-MIS0
Noninvasive PET imaging with hypoxic
marker such as 18F-MISO4 can evaluate
the tumor and regional disease in a
“snapshot” fashion and can provide serial
quantitative measurements of hypoxia. This
can be useful for tumor hypoxia imaging for
quantifying regional hypoxia and evaluation
of therapy-relevant tumor oxygenation
especially for radiotherapy.
Comparison of (A) FDG scan, (B) 18F-F-MISO scan
in a patient with adenocarcinoma of the lung.
Sodium fluoride
bone scan.
References:
1. Eur J Nucl Med Mol Imaging. 2007, 34, 185.
2. J Nucl Med., 2003, 44, 213.
3. (a) Clin Cancer Res., 2007, 13, 3552. (b) J Nucl Med.,
2007, 48, 1945. (c) Clin Cancer Res., 2004, 10, 1965.
(d) J Nucl Med., 2003, 44, 1297. (e) J Nucl Med., 2003,
448, 1426.
4. (a) Clin Cancer Res., 2006, 12, 5435. (b) Clin Cancer
Res., 2008, 14, 2623.
5. (a) Neuropsychopharmacology, 2007, 32, 450. (b) JNucl
Med, 2000, 41, 65.
6. J Nucl Med., 2005, 46, 1650.
Dr Maung Maung Saw
MBBS, PhD
Clinical Director
Singapore Radiopharmaceuticals Pte Ltd
5
 Image of the Month
51 year old lady with history
of right hemicolectomy for
metastatic carcinoid. Gallium-68
DOTATATE follow-up PET scan
reveals tiny peritoneal metastasis
(top image) with another
metastatic deposit in the left
ovary (bottom image)

New Doctors
New Radiochemist:

Dr Maung Maung Saw

We are pleased to announce that Dr Maung Maung Saw has joined us as
Radiochemist at Singapore Radiopharmaceuticals Pte Ltd.
Dr Maung obtained his medical degree from The Institute of Medicine in
Myanmar in 1982. After various postings, he then joined the Department of
Nuclear Medicine and PET of Singapore General Hospital in 2000.
He has served as a radiopharmacy expert for IAEA since 2001 to various countries
such as Vietnam, Mongolia, Thailand, The Philippines and to Egypt to train local
staff on the use of 188Re-radiopharmaceuticals and to promote radiopharmacy.
In 2006, he joined NUS, and held a joint appointment between NUS and NUH. This involved the
Departments of Chemistry, Diagnostic Radiology and Diagnostic Imaging of NUH and NUS. He is also an
associate member of Medicinal Chemistry Program of NUS.
Dr Maung has been involved with clinical trials since 2006 in the capacity as a Principal and Co-Principal
Investigator. The research projects were on the development of new radiopharmaceuticals and probes for
molecular imaging. In the same year he obtained his PhD in Radiochemistry.
He has also published many clinical papers and has authored IAEA monographs.
His email address is mmsaw@radiopharmaceuticals.com.sg.
6

“Time-of-Flight” PET Technology Improves Detection and Images
I
T was only six years ago that PET/CT was named TIME
magazine’s “Invention of the Year.” Yet in that short
time, PET/CT has seen unprecedented growth as well as
tremendous changes in the technology of both the PET and
CT components.
The technological changes in PET have included new
crystal detector material and faster electronics that together
have greatly improved PET’s overall sensitivity and efficiency.
The CT technology, which began with a simple single or dual-
slice detector, is now available with several options, including
a 64-slice detector system. The progress of both PET and CT
technology has established the foundation for today’s PET/
CT systems that can now provide unprecedented speed,
quality and diagnostic information.
The most recent development in the current generation of
PET/CT system is the introduction of the first clinical PET/CT
scanner with time-of-flight technology released by Phillips
Medical Systems (Highland Heights, OH). Time-of-flight
technology improves detection of the coincident event — the
essence of PET imaging.
The coincident event begins with a positron colliding
with an electron. The two particles annihilate, resulting
in two gamma photons that are ejected at trajectories
approximately 180 degrees from one another. Crystals at
opposite ends of the gantry detect the gamma photons,
and the “coincident event” is recorded. The electronics of
the PET system determine that the origin of the positron-
electron interaction took place somewhere along the line-of-
response between the two detectors. However, what has not
been taken into account until now is that the two photons
do not actually interact with the crystals at exactly the same
time. The Photon traveling the shorter distance will interact
Philips TruFlight: The solution to better PET Imaging
In conventional PET imaging, its possible TruFlight technology uses the actual
only to know that a coincident event has time difference between the detection
taken place on the line of response, but of coincident events to more accurately
not the actual location of the event. identify the origin of the annihilation.
Better identification leads to a quantifiable
improvement in image quality.
New Technology
with its crystal slightly before the second coincident photon
reaches its detector. This time differential is dependent on
the location of the position annihilation event — and, of
course, the more precisely that location can be determined,
the better the PET image will be. Therefore, if the difference
in time of detection can be recorded, the PET system can
determine the location of the positron-electron interaction
along the line-of-response between detectors, hence
“time-of-flight” technology. Time-of-flight technology takes
advantage of the difference between the detection times of
each gamma photon to more accurately locate the origin of
the annihilation event.
While it is only recently that time-of-flight has generated
tremendous interest, this concept is not new. Time-of-flight
was developed over 20 years ago with the first publication by
Mullani et. al. appearing in The Journal of Nuclear Medicine in
1980. Early in the 1980s this technology was developed and
implemented in research scanners. However, slow crystals and
electronic have kept time-of-flight technology from being used
to any great degree with clinical scanners. Current generation
PET detection with LSO and LYSO crystals and ultra-fast
electronics now provide the speed and efficiency necessary to
take advantage of time-of-flight technology.
The performance of the first clinical time-of-flight PET/CT
scanner was presented this year at the SNM’s 53rd Annual
Meeting by Surti et al., from the University of Pennsylvania.
The data presented indicate that their time-of-flight scanner
with LYSO crystals provides for improved diagnostic accuracy
regardless of the patient size. By utilizing time-of-flight
technology to better locate the origin of the annihilation event,
small or average size patients can be imaged faster without
the loss of diagnostic information. However perhaps the
greatest advantage of time-of-flight technology
is in imaging larger patients. Imaging large or
obese patients can be challenging; however Surti
et al. found that time-of-flight technology actually
improves both the sensitivity and specificity in
cancer lesion detection in these larger, harder-
to-image patients. With obesity rates higher than
ever, this technology should prove extremely
valuable.
Time-of-flight technology is just the latest
example of how rapidly PET/CT is evolving. One
can image what changes or developments might
take place over the next six years; however, one
thing can be certain, PET/CT technology will
continue to improve.
This article was reprinted from snmts newslatter
7
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Special Interest:
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