Continued on page 2. See Plaque. Continued on page 4. See Amyloid Imaging.
FDA Moves Forward
on Imaging Amyloid
in the Brain
A more extensive version of the article was published in the
March issue of The Journal of Nuclear Medicine (2009;50:
331–334) as the Focus on Molecular Imaging feature.
MI in the News
Capitol Hill Day
New RECIST Guidelines
The past several years
have seen tremendous
advances in the devel-
opment of new radiop-
harmaceuticals for mole-
Clinical Feasibility of Molecular Imaging of
Plaque Inflammation in Atherosclerosis
By Nobuhiro Tahara, University of California, Irvine, Calif., and Kurume
University School of Medicine, Kurume, Japan; Tsutomu Imaizumi, Kurume
University School of Medicine, Kurume, Japan; Renu Virmani, Cardiovascular
Pathology Institute, Gaithersburg, Md.; and Jagat Narula, University of California,
Molecular imaging of various components of atherosclerotic plaques has been pro-
posed, and proof of principle has been demonstrated in experimental models of dis-
ease (1). These preclinical studies have predominantly targeted plaque inflammation
with the premise that the extent of inflammation would determine the vulnerability of
the plaque to rupture. Plaque inflammation has been detected by targeting alterations
in monocytes that facilitate their migration to the neointima, ensure efficient scaveng-
ing of insudated lipid, oversee their transformation to foam cells or mediate cell death
Molecular targets have also included events that are associated with or consequent
to inflammation, such as production of cytokines and metalloproteinases. Although
these experimental molecular imaging studies have offered significant promise, trans-
lational data in the clinical setting has just started to emerge. Clinical studies of mo-
lecular targeting are the major focus of the following review.
We have referred to some of the early molecular imaging attempts that labeled white
blood cells to follow their localization and labeled lipoproteins to trace their destina-
tion in the inflammatory cells in plaques (1). Even though the incorporation of radio-
labeled components in the plaque may not have been adequate, these studies created
a sound foundation for the development of imaging strategies of the future.
Pathologic Basis of Inflammation Imaging
Vulnerable plaques have typically large necrotic cores that are covered by thin fi-
brous caps (2). Many foam cells are seen around the necrotic cores. There is extensive
inflammation within the fibrous caps; the more macrophages, the thinner the cap.
Migration of monocytes to the subintimal layers of the plaque is associated with de-
gatewaythe newsletter of the snm molecular imaging center of excellence
Vol. 3 | Issue 1 | 2009•1
cular imaging with positron emission tomog-
raphy (PET). Despite the large number of
pre-clinical and early clinical studies in the
literature, however, only one PET radiophar-
maceutical for molecular imaging—fluorode-
oxyglucose (FDG)—is widely used clinically.
A recent meeting convened by the Food and
Drug Administration (FDA) provided opti-
mism for the introduction of new molecular
imaging agents for clinical use, particularly
for imaging amyloid in the brain.
Radiopharmaceutical manufacturers ap-
proached the FDA requesting advice about the
design of phase 3 clinical studies that would
support marketing approval of a radiophar-
maceutical to detect amyloid deposition in the
brain. As a result of this request, the FDA con-
vened a meeting of its Peripheral and Central
Nervous System Drugs Advisory Committee
on Oct. 23, 2008. Committee membership
was augmented by several members of SNM,
including Henry Royal, MD, of Washing-
ton University, St. Louis; Harvey Zeissman,
MD, of Johns Hopkins University; and Peter
Herscovitch, MD, National Institutes of
Health. Representatives from industry spon-
sors—Avid Radiopharmaceuticals Inc., Bayer
Healthcare Pharmaceuticals Inc. and GE
Healthcare—presented their 18
pharmaceuticals for amyloid imaging.
The FDA asked the committee to consider
• To what extent, if any, would an indi-
cation for use of an in vivo diagnostic
Peter Herscovitch, PhD
mi gateway | 2009
Plaque. Continued from page 1.
velopment of receptors for chemoattractant factors, such as mono-
cyte chemotactic protein-1 (MCP-1); adhesion molecules, such as
vascular cell adhesion molecule-1 (VCAM-1) (1); and expression of
scavenger receptors, including SRAI/II, CD68 and FcRIII.
In addition to upregulation of various surface receptors, foam
cells in the neointima release numerous cytokines, such as inter-
leukin-1, tumor necrosis factor-α and MCP-1 (3). Activated mac-
rophages also release metalloproteinases and other proteolytic en-
zymes, such as cathepsins, which lead to degradation of the matrix,
thinning of the fibrous cap and positive outward remodeling of
the vessel wall. Cell death is commonly observed in the vulner-
able plaque; macrophage death leads to expansion of the necrotic
core and perpetuates plaque instability (4). More than 40 percent of
macrophages at the site of fibrous cap rupture are also in the pro-
cess of cell death by apoptosis. It has been reported that dying mac-
rophages may produce tissue factor (5) and metalloproteinases.
Molecular Imaging of Plaque Inflammation
The characteristic alterations that evolve during monocyte infil-
tration to the neointima and lipoprotein ingestion vary based on
different phases of plaque development and have been targeted
successfully by radiolabeled autologous leukocytes (Fig. 1) (6),
low-density lipoprotein (LDL) (7) and Fc fragments of immuno-
globulin (8). More recent experimental studies have used radio-
labeled ligands of cytokine and adhesion molecule receptors, in-
cluding MCP-1 and VCAM-1, or cytokines released by infiltrating
macrophages, such as metalloproteinase (1).
It is not entirely clear if such a characterization would be of clini-
cal significance or which candidate molecule would be most infor-
mative. However, few recent correlative studies have demonstrated
that the presence of activated or apoptotic macrophages are associ-
ated with culprit lesions underlying an acute coronary event. The
macrophages with high respiratory burst have been clinically rec-
ognized by 18
F-labeled FDG imaging (9), and dying macrophages
by technetium-99m annexin-A5 (AA5) (Fig. 1) (4,10). Presence of
active inflammation should predict plaque vulnerability if informa-
tion is obtained before the occurrence of an acute event.
FDG Imaging of Plaque Instability
PET imaging studies for localization of malignant tumors have
reported incidental 18
F-FDG uptake in the carotid, coronary, iliac
and femoral arteries, and thoracic and abdominal aorta in up to
50 percent of patients. In prospectively studied patients with ul-
trasonic evidence of carotid atherosclerosis, FDG uptake was seen
in 30 percent of patients (11). Glucose uptake in atherosclerotic
plaques has been hypothesized to represent inflammatory activ-
ity, and there is a direct correlation between carotid FDG uptake
(expressed as the target-to-background ratio of standardized up-
take value) and macrophage density (mean percentage staining of
CD68-positive cells) in the carotid endarterectomy specimens (r
= 0.85, P < 0.0001) (12). 18
F-FDG uptake does not correlate with
plaque area, thickness or smooth muscle cell density.
Serial prospective 18
F-FDG PET studies have reported an excel-
lent interobserver, intraobserver and interscan reproducibility (13).
The effect of statin intervention on FDG uptake has been reported
in patients with carotid atherosclerosis (14), wherein the follow-up
PET scans revealed significant reduction in FDG accumulation af-
ter therapy. FDG uptake, however, does not resolve in response to
only dietary modifications (14).
FIGURE 1. Clinical imaging of plaque inflammation. (A) Imaging of macrophage
prevalence with Tc-99
m-LDL, (B) 18
F-FDG and (C) Tc-99
m annexin A5.
Although various case reports and retrospective studies (15)
have demonstrated anecdotal 18
F-FDG uptake in coronary arteries
in oncologic patients, a recent prospective 18
F-FDG PET study with
multislice CT demonstrated the feasibility of precise 18
ization in coronary arteries (Fig. 2) (16). In this study, myocardial
F-FDG uptake was almost entirely suppressed (by a high-fat diet
and restriction of carbohydrate meals for one day before the study
and administration of β-blockers on the day of the study) for better
The study also took advantage of CT angiography and enrolled
patients who had undergone coronary stent implantation for acute
coronary syndrome or chronic stable angina; CT angiography and
stent location allowed precise coregistration of FDG uptake at the
plaque site. Culprit lesions in acute coronary events demonstrated
significantly higher FDG uptake (Fig. 2) than did target lesions in
chronic disease. Although it will be necessary to develop measures
to contain radiation burden imposed by combined PET/CT stud-
ies, this study holds a promise of radical strategic shift in coronary
artery disease management.
Annexin Imaging of Inflamed Plaques
Because apoptotic cells express phosphatidylserine on their cell
surface and AA5 has a high affinity for binding to phosphatidyl-
serine, imaging with 99
mTc-labeled AA5 has been used to evaluate
the feasibility of the detection of unstable plaques. AA5 has been
extensively used for noninvasive imaging of experimental athero-
sclerotic lesions (4). There was a direct correlation of AA5 uptake
with macrophage burden and the magnitude of histologically veri-
It was subsequently indicated that pharmacologic interven-
tion using stains and caspase inhibitors could reduce the extent of
apoptosis in experimental atherosclerosis models (17,18). Studies
of porcine atherosclerosis have demonstrated the feasibility of coro-
nary imaging with radiolabeled AA5 (19). AA5 has also been used
Continued on page 3. See Plaque.
Plaque. Continued from page 2
mi gateway | 2009 3
in a small pilot study for imaging of carotid atherosclerosis in
patients with recent or remote cerebrovascular accidents (10).
AA5 uptake was reported only after recent cerebrovascular
accidents and not seen in patients being treated with statins.
AA5 binding was histologically localized to apoptotic mac-
rophages and also to the red blood cell membranes embedded
in necrotic cores. Radiolabeling of AA5 with PET-compatible ra-
diotracers, such as 124
I and 18
F, is under way and may provide
better avenues for coronary vascular imaging.
The likelihood that atherosclerotic plaques will result in acute
vascular events is intimately associated with the morphologic
traits of the plaque and the extent of inflammation. A noninva-
sive strategy designed to monitor the extent of plaque inflam-
mation may allow identification of unstable plaques, and serial
interrogation may determine the efficacy of intervention.
F-FDG uptake, which has been commonly used in onco-
logic practice, offers information about plaque inflammation
and allows serial investigation. The feasibility of coronary im-
aging with 18
F-FDG has evoked tremendous enthusiasm in the
imaging community. Successful 18
F-FDG imaging of coronary
arteries has also encouraged investigation with other promising
molecules, such as annexin. It is conceivable that the high-risk
patients identified by clinical tools, including genetic informa-
tion and biomarkers, will in the future be more accurately risk-
stratified by imaging targeted at morphologic and functional
characterization of high-risk plaques.
1. Narula J, Garg P, Achenbach S, Motoyama S, Virmani R, Strauss HW. Arith-
metic of vulnerable plaques for noninvasive imaging. Nat Clin Pract Cardio-
vasc Med. 2008;5(suppl 2):S2–S10.
2. Burke AP, Farb A, Malcom GT, Liang YH, Smialek J, Virmani R. Coronary
risk factors and plaque morphology in men with coronary disease who died
suddenly. N Engl J Med. 1997;336:1276–1282.
3. Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868–874.
4. Kolodgie FD, Petrov A, Virmani R, et al. Targeting of apoptotic macrophages
and experimental atheroma with radiolabeled annexin V: a technique with
potential for noninvasive imaging of vulnerable plaque. Circulation. 2003;
5. Hutter R, Valdiviezo C, Sauter BV, et al. Caspase-3 and tissue factor expression in
lipid-rich plaque macrophages: evidence for apoptosis as link between inflamma-
tion and atherothrombosis. Circulation. 2004;109:2001–2008.
6. Virgolini I, Müller C, Fitscha P, Chiba P, Sinzinger H. Radiolabelling autologous
monocytes with 111-indium-oxine for reinjection in patients with atherosclerosis.
Prog Clin Biol Res. 1990;355:271–280.
7. Lees AM, Lees RS, Schoen FJ, et al. Imaging human atherosclerosis with 99
labeled low density lipoproteins. Arteriosclerosis. 1988;8:461–470.
8. Fischman AJ, Rubin RH, Delvecchio A, Strauss HW. Imaging of atheromatous
lesions in the iliac and femoral vessels: preliminary experience with 111
human subjects [abstract]. J Nucl Med. 1989;30(suppl):817P.
9. Rudd JHF, Warburton EA, Fryer TD, et al. Imaging atherosclerotic plaque inflam-
mation with [18F]-fluorodeoxyglucose-positron emission tomography. Circula-
10. Kietselaer BL, Reutelingsperger CP, Heidendal GA, et al. Noninvasive detection
of plaque instability with use of radiolabeled annexin A5 in patients with carotid-
artery atherosclerosis. N Engl J Med. 2004;350:1472–1473.
11. Tahara N, Kai H, Yamagishi S, et al. Vascular inflammation evaluated by [18F]-
fluorodeoxyglucose positron emission tomography is associated with the meta-
bolic syndrome. J Am Coll Cardiol. 2007;49:1533–1539.
12. Tawakol A, Migrino RQ, Bashian GG, et al. In vivo 18
tron emission tomography imaging provides a noninvasive measure of carotid
plaque inflammation in patients. J Am Coll Cardiol. 2006;48:1818–1824.
13. Rudd JH, Myers KS, Bansilal S, et al. 18
Fluorodeoxyglucose positron emission to-
mography imaging of atherosclerotic plaque inflammation is highly reproducible:
implications for atherosclerosis therapy trials. J Am Coll Cardiol. 2007;50:892–
14. Tahara N, Kai H, Nakaura H, et al. The prevalence of inflammation in carotid
atherosclerosis: evaluation by FDG-PET. Eur Heart J. 2007;28:2243–2248.
15. Alexanderson E, Slomka P, Cheng V, et al. Fusion of positron emission tomog-
raphy and coronary computed tomographic angiography identifies fluorine 18
fluorodeoxyglucose uptake in the left main coronary artery soft plaque. J Nucl
16. Rogers IS, Figueroa AL, Nasir K, et al. Assessment of coronary segment inflam-
mation with combined 18-fluorodeoxyglucose positron emission tomogra-
phy and 64-slice multidetector computed tomography [abstract]. Circulation.
17. Hartung D, Sarai M, Petrov A, et al. Resolution of apoptosis in atherosclerotic
plaque by dietary modification and statin therapy. J Nucl Med. 2005;46:2051–
18. Sarai M, Hartung D, Petrov A, et al. Broad and specific caspase inhibitor-induced
acute repression of apoptosis in atherosclerotic lesions evaluated by radiolabeled
annexin A5 imaging. J Am Coll Cardiol. 2007;50:2305–2312.
19. Johnson LL, Schofield L, Donahay T, Narula N, Narula J. 99
mTc-annexin V imag-
ing for in vivo detection of atherosclerotic lesions in porcine coronary arteries. J
Nucl Med. 2005;46:1186–1193.
FIGURE 2. 18F-FDG uptake in coronary inflammation seen (A) incidentally in a patient
evaluated for malignant disease, and (B) in a prospective study after coronary inter-
vention for acute coronary syndrome. Figure 2B was provided by Ahmed Tawakol.
Clinical Trials Workshop at
SNM Annual Meeting
The content from the recent, sold-out workshop on the SNM Clinical
Trials Network will be repeated in a one-day categorical at SNM’s
56th Annual Meeting in Toronto, June 13, 2009. There will also be a
CE Session on Sunday devoted to manufacturing issues.
If you missed the February workshop, this is your chance to get
acquainted with the SNM Clinical Trials Network and learn how you
can provide imaging services to therapeutic multicenter clinical
trials or take advantage of SNM’s multicenter IND for FLT imaging.
mi gateway | 20094
Amyloid Imaging. Continued from page 1.
radiopharmaceutical for the “detection of cerebral
amyloid” provide useful clinical information?
• If an in vivo diagnostic radiopharmaceutical would
be clinically useful in detecting cerebral amyloid,
against what “standard of truth” should its perfor-
mance be compared in phase 3 clinical studies?
• What are the strengths and weaknesses of the phase
3 study designs presented by the three industry
A lively discussion ensued among panel members, FDA
staff and industry representatives. It should be noted that
none of the sponsors was proposing that these agents
should have a disease-specific marketing label indication;
for example, for diagnosis of Alzheimer’s disease (AD). The
committee agreed that a PET scan showing absent brain
amyloid could provide clinically useful information in rul-
ing out a diagnosis of AD. They felt, however, that a posi-
tive test would have limited utility because amyloid can be
present in conditions other than AD. The committee also
agreed that an amyloid imaging agent could be a valuable
tool in clinical research; for example, in the development
of drugs to treat cerebral amyloid deposition in AD.
Extensive discussions followed regarding what the
standard of truth should be in phase 3 clinical studies of
an amyloid imaging agent. The committee overwhelming-
ly agreed that the standard of truth should be histopatho-
logical confirmation of the presence of amyloid in autopsy
studies in subjects who had an antemortem amyloid scan,
although such studies might be logistically difficult to ar-
range. It was felt that a clinical diagnosis of AD, even if
made by a specialized team using research criteria, was
not an appropriate gold standard for the presence of brain
This meeting provided important guidance to industry
with regard to phase 3 trials of PET radiopharmaceuti-
cals to detect cerebral amyloid. It will facilitate bringing
such radiopharmaceuticals into the clinic to help in the
management of patients with dementia. It is noteworthy
that the discussion did not focus on a disease-specific in-
dication—the diagnosis of AD. Rather, the committee was
asked to consider an indication relating to the ability of an
agent to detect a biochemical or pathological process asso-
ciated with a disease. Therefore, this meeting had broader
implications for the introduction of molecular imaging
agents into the clinic.
Several other PET radiopharmaceuticals exist, especially
in the area of oncology, that may have an indication based
on their biochemical or pathological imaging character-
istics rather than for the diagnosis of a specific disease.
Examples include agents to image tissue hypoxia, cellu-
lar proliferation and angiogenesis. This meeting provided
a model for how other molecular imaging agents might
receive approval for clinical use.
Peter Herscovitch, MD
National Institutes of Health
MI Gateway presents a selection of top molecular imaging papers drawn from the wide
spectrum of scientific and medical disciplines engaged in research in the field. This
feature gives a summary of selected papers and links to the original publication on
PubMed. Click the titles (or copy the URL to your browser) to read the complete summary
and see links to the PubMed abstract. The full list of selected research and review papers
is available at www.molecularimagingcenter.org > LatestResources.
Contrast Agents for Enhanced MR Imaging of Macrophages
Chen et al. from the Mount Sinai School of Medicine (New York, NY)
reported in the November issue of Contrast Media and Molecular Imag-
ing (2008;3:233–242) on the incorporation of an apolipoprotein–E–
derived lipopeptide (P2fA2) into high-density lipoprotein (HDL) MR
imaging contrast agents for enhanced imaging of macrophages in
atherosclerosis. The group had previously presented data in several
articles on targeted molecular probes for MR atherosclerosis imag-
ing (e.g., Circulation. 2008;117:3206–3215; Proc Natl Acad Sci USA.
“Quench and Chase” Strategy for Molecular Imaging
Ogawa and colleagues from the National Cancer Institute (Bethes-
da, Md.) described in the January issue of Bioconjugate Chemistry
(2009;20:147–154) the tumor-specific detection of an optically tar-
geted antibody combined with a quencher-conjugated neutravidin
“quencher-chase” in a dual strategy to improve target-to-nontarget
ratios for molecular imaging in cancer. The research was conducted
in response to challenges posed by the low tumor-to-background
ratios in many monoclonal antibody studies and by successes in the
use of avidin as a “chase” to clear unbound antibody and decrease
background signal. … (19072537)
Nanoprobes for the Imaging of Angiogenesis
Almutairi and colleagues from the University of California, Berkeley,
reported in the Jan. 20 issue of the Proceedings of the National Academy
of Sciences of the United States of America (2009;106:685–690) on
development of and initial studies with a biodegradable positron-
emitting dendritic nanoprobe targeted at αn
integrin for the non-
invasive imaging of angiogenesis. The design and construction of
the nanoprobe was described in detail, including a dendritic core
functionalized for labeling with radiohalogens. The nanoscale design
enabled a 50-fold enhancement of the probe’s binding affinity to αn
integrin receptors. …
Color-Coded Fluorescent Protein Imaging of Angiogenesis
Amoh and colleagues from the Kitasato University School of Medicine
(Kanagawa, Japan) reported in a recent issue of Current Pharmaceuti-
cal Design (2008;14:3810–3819) on the development and validation
of 3 fluorescent imaging models of tumor angiogenesis, collectively
labeled as Angio Mouse, that can quantitatively determine the efficacy
of antiangiogenesis compounds. In the first model, nonluminous
induced capillaries were clearly visible against the model’s bright green
fluorescent protein (GFP) in tumors examined either intravitally or by
whole-body imaging. …
Albert J. Sinusas, MD
mi gateway | 2009 5
NIH Symposium Explores Multimodality
Cardiovascular Molecular Imaging
The MICoE Education Task Force met in St. Louis last December
to discuss changes that would incorporate molecular imaging
into the nuclear medicine curriculum and the development of a
scientists’ curriculum in molecular imaging. From left: Marybeth
Howlett, director of the MICoE; Bennett Greenspan, MD; Jeffrey
Norenberg, PharmD; Michael Graham, PhD, MD; Kurt Zinn, PhD;
Heather Jacene, MD; Carolyn Anderson, PhD; and Lynn Barnes,
SNM’s director of education.
Molecular imaging techniques
Micro- and macro-PET/SPECT/
Natcher Auditorium . National Institutes of Health . Bethesda, Maryland . April 30–May 1, 2009
the latest research…
the most promising clinical techniques…
the future of cardiovascular care
See the Future of Cardiovascular Care…
This innovative symposium will introduce you to the latest cardiovascular
imaging research and the most promising clinical techniques. Learn how
noninvasive targeted molecular imaging can facilitate patient stratification
and early detection to create a personalized approach to the evaluation and
management of cardiovascular disease.
Hear from Noted Speakers…
Listen to renowned molecular imaging experts from multiple scientific
disciplines, including chemistry, engineering, physics, molecular biology,
cardiovascular physiology, and imaging sciences. Learn about the latest
advances in gene expression, atherosclerosis, angiogenesis, imaging probes,
stem cell research, and more.
Be Involved—Be at the Forefront of Medical Advancement
This gathering of leading researchers in the field will help chart the
direction of cardiovascular molecular imaging for the next decade.
Register today at www.snm.org/cvmi2009
Interested in sponsoring this dynamic meeting? Contact Marybeth Howlett at
firstname.lastname@example.org for information on sponsorship opportunities.
Special Session Added Friday Night!
FDA Requirements for Manufacturing PET
Radiopharmaceuticals is co-sponsored by
the International Partnership for Critical
Markers of Disease (CMOD).
For more information or to register, see
“Special Session” at www.snm.org/cvmi2009.
SNM and the MICoE are sponsoring a
symposium on multimodality cardiovas-
cular molecular imaging April 30–May 1 at
the National Institutes of Health (NIH).
This symposium addresses a shift in em-
phasis from treatment to prevention, in
part to control the escalating costs of health
care. It will build on a similar and success-
ful symposium held at NIH in 2004 (J Nucl
Med. 2004;45:28N) and will bring together individuals
from multiple scientific disciplines with the goal of promoting
the emerging field of cardiovascular molecular imaging.
The 2004 conference served as the basis for the first text-
book dedicated to the field of cardiovascular molecular imag-
ing. The 2009 meeting is designed to continue this momentum
and to attract individuals from both the basic science and clini-
cal communities, with a special emphasis on encouraging par-
ticipation by junior scientists. A series of papers generated by
the speakers/moderators for each of the sessions will be pub-
lished by The Journal of Nuclear Medicine as a special supple-
ment on cardiovascular molecular imaging.
The meeting will include a series of lectures by scientists and
physicians, panel discussions, and an abstract poster session.
Speakers have been chosen from multiple scientific disciplines,
including chemistry, engineering, physics, molecular biology,
cardiovascular physiology and imaging sciences. The agenda
focuses on advances in targeted imaging of the cardiovascular
system, including imaging of cardiovascular receptors, stem
cell therapy, vascular biology, myocardial metabolism, ath-
erosclerosis, angiogenesis, cardiomyopathies, ischemia and
The symposium is designed to help disseminate the latest
cardiovascular imaging research and the most promising clini-
cal techniques. Noninvasive, targeted molecular imaging can
facilitate the evaluation and management of cardiovascular
disease, provide a basis for patient stratification, and increase
the accuracy of early detection. Molecular imaging will be a
key technology in creating the world of personalized medicine.
This gathering of leading researchers in the field will help chart
the direction of cardiovascular molecular imaging for the next
You can find more information about registration at
Albert J. Sinusas, MD
May 1, 2009
MI Gateway presents a sampling of research and news of interest to the
community of molecular imaging scientists. Click the headlines to read the
full story if reading online, or access these articles using the URLs provided.
More molecular imaging news is available daily at www.molecularimaging
center.org > Latest News.
in the news
FDG-PET provides new clues on
A U.S. study on patients with at least three
cardiovascular risk factors showed that
FDG-PET imaging can help in determining
the relationship between atherosclerotic
plaque inflammation, and calcification and
vascular risk factors. The findings show
“that arterial FDG-PET imaging can
provide new insights into the pathobiology
of atherosclerosis,” the researchers said.
Researchers enhance PET/CT imaging
with radiolabeled nanoparticles
Researchers used a chemical reaction called
“click chemistry” to add the radioisotope
F to iron oxide nanoparticles used in
tumor imaging. A test on mice showed
that the radiolabeled nanoparticles can
be easily detected using PET/CT. The
researchers plan to explore the potential of
the labeled nanoparticles as tumor-imaging
Johns Hopkins to provide
Johns Hopkins’ Brain Science Institute in
Baltimore is underwriting the Center for
Translational Imaging (CTI), which aims
to channel experience from Hopkins’
imaging-dedicated centers into a universi-
ty-wide understanding and use of imaging
techniques for neuroscience research.
mi gateway | 20096
The first formal revision of specific guidelines—Response Evaluation
Criteria In Solid Tumors, or RECIST—used by clinicians to measure tumor
size and response to treatment was published Jan. 20, 2009, in a special
issue of the European Journal of Cancer. According to the authors, the
revisions will ease the workload involved in running clinical trials without
compromising study outcomes.
RECIST were first published in 2000 and are used by investigators in
phase 2 and phase 3 clinical trials of new anti-cancer drugs as a way
of measuring the efficacy of the treatment. Tumor shrinkage (objective
response) and time to the development of disease progression are both
important endpoints in trials, and, increasingly in recent years, trials have
been using time-to-progression (or progression-free survival) as their
main endpoint on which to base conclusions about the efficacy of a drug.
The new RECIST (RECIST 1.1 to distinguish from the original RECIST)
answer some of the questions and issues that have arisen since 2000 as
a result of changing methodologies and available treatments, as well as
help improve the consistency and standardization of trials.
New Criteria Will Ease Workloads in Clinical Trials
Talk Back to Congress!
Join SNM and the MICoE boad of di-
rectors in Washington, D.C., April 20–
21, for SNM’s Capitol Hill Day. This is
your chance to educate Congress on the
value of molecular imaging and the ur-
gent need for funding and support.
Carolyn Anderson, PhD, on
Capital Hill, June 2007
During the 2007 Annual Meeting in Washington, D.C., I par-
ticipated in the first Capitol Hill Day, and it was a completely
engaging and gratifying experience. The training we received
from SNM’s legislative consultants prior to our congressional
staff meetings was right on target. They prepared us with talk-
ing points and coached us on how to make our points clearly
I forged a good relationship with the staff of Congressman
Russ Carnahan, (D-Mo.), the representative from my home
district. His office has stayed in touch with me since on issues
involving science and medicine. Even better, I think we actually
made a difference in legislation and funding.
Join us this year on Capitol Hill and help make a differ-
ence! Training will be held Monday morning, April 20, in
Washington, D.C., with Capitol Hill visits scheduled Monday
afternoon and Tuesday. If you are interested, send an e-mail
to email@example.com before April 10. The SNM health policy and
regulatory affairs department will schedule a meeting with your
members of Congress or their staff.
Carolyn Anderson, PhD
Finding a dynamic and knowledgeable speaker is always a
challenge, and when you are in charge of organizing a meeting,
you want to ensure that the meeting is as engaging as it is infor-
The SNM speakers bureau—Inside MI—was established to
provide speakers who can convey the excitement and promise
of molecular imaging to a variety of audiences. Patient groups,
medical societies, students of medicine or health-related pro-
fessions, SNM chapters, and other groups with an interest in
medical imaging can request a molecular imaging presentation
tailored to their interests and level of expertise.
One of the first members to take advantage of this new ser-
vice was Lyn Mehlberg, CNMT and SNMTS past president, who
served as program chair for the 2008 Central Chapter spring
meeting. Thomas Meade, PhD, professor of chemistry, neuro-
biology and physiology at Northwestern University (Evanston,
Ill.) was the speaker Inside MI provided. His research focuses on
molecular imaging of in-vivo gene expression and intracellular
messengers, transition metal enzyme inhibitors and electronic
“He was fantastic,” Mehlberg said. “He may have been talking
about chemistry, but he had us laughing so hard we were cry-
ing and literally on the edge of our seats. His explanations were
so clear my mother could have followed them, and his graphics
Inside MI speakers come from top health-care centers and
academic institutions, including Cedars Sinai Medical Center
in Los Angeles, Calif.; the University of Texas M. D. Anderson
Cancer Center in Houston; the University of Pennsylvania in
Philadelphia; Yale University School of Medicine, New Haven,
Conn.; and Memorial Sloan-Kettering in New York City. The
Inside MI program maintains a list of individuals with exper-
tise in multimodality imaging, optical imaging, ultrasound,
MRI/MRS, biomarkers, gene/cell therapy, small animal imaging,
infection/inflammation, radiochemistry, nonradioactive molec-
ular imaging agents, contrast agents, and instrumentation and
data analysis. Imaging specialists in cardiology, neurology and
oncology are also available.
Funded by SNM’s “Bench to Bedside” campaign, Inside MI
covers both travel expenses and speakers’ honoraria. Speakers
are assigned to events based on topic requests and proximity.
SNM staff will arrange logistical details and payments.
“Inside MI provided a wonderful opportunity to bring a re-
nowned thought-leader in molecular imaging to my chapter
meeting,” Mehlberg said. “Dr. Meade was absolutely captivating
as he shared his vision of where molecular imaging will go dur-
ing the next decade. The speakers bureau is a valuable resource
for bringing this level of expertise to our members.”
To request an Inside MI speaker—or to apply as an Inside
MI expert—contact Jennifer Rice at firstname.lastname@example.org
or 703-742-5498. You can learn more about the program at
mi gateway | 2009 7
SNM Speakers Bureau Brings Out the Best
More than 150 physicians, imagers and
pharmaceutical developers convened in
Clearwater, Fla., Feb. 8–9, for an intensive
workshop examining the need for stream-
lined drug discovery through the integra-
tion of imaging biomarkers into multi-
center clinical trials.
Stakeholders from every facet of the drug
discovery process came together at the
SNM Clinical Trials Network Community
Workshop to learn how the new network
can facilitate faster and more cost-effective
drug development through the integra-
tion of imaging biomarkers into phase 1,
2, 3 and 4 therapeutic clinical trials. The
workshop outlined details of participation
in the network and examined the critical
need for standardization and harmoniza-
tion across imaging sites.
“After listening carefully to the needs
of these various but interconnected com-
munities, SNM has focused on the issue
of limited harmonization of imaging pro-
tocols between multiple imaging centers,”
said SNM President Robert W. Atcher,
PhD, MBA. “SNM will ensure the use of
a consistent methodology and protocol
across the multiple clinical trial sites. That
is key to quality data generation and ul-
timate FDA approval of investigational
The comprehensive workshop was held
immediately after SNM’s Mid-Winter Edu-
cational Symposium and featured presen-
tations and discussions about methods
and shortcomings of current drug devel-
opment practices, the potential for im-
aging biomarkers in multicenter clinical
trials, the role of the SNM Clinical Trials
Network in drug development, and funda-
mentals of participation in the network.
For more information about the SNM
Clinical Trials Network, please visit
SNM Molecular Imaging Summit Introduces Clinical Trials Network