www.molecularimagingcenter.org/ mi

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 LitBriefsp. 4

Cardiovascular Imaging Symposium

p. 5

MI in the News

Capitol Hill Day

New RECIST Guidelinesp. 6

Speaker’s Bureau

Clinical Trials Network

p. 7

Late-Breaking Newsp. 8

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 AtherosclerosisBy 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, Irvine, Calif.

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 (1). 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 18F-labeled radio-pharmaceuticals for amyloid imaging. The FDA asked the committee to consider three questions:

• 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.

2

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 18F-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 18F-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). 18F-FDG uptake does not correlate with plaque area, thickness or smooth muscle cell density. Serial prospective 18F-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-99m-LDL, (B) 18F-FDG and (C) Tc-99m annexin A5.

Although various case reports and retrospective studies (15) have demonstrated anecdotal 18F-FDG uptake in coronary arteries in oncologic patients, a recent prospective 18F-FDG PET study with multislice CT demonstrated the feasibility of precise 18F-FDG local-ization in coronary arteries (Fig. 2) (16). In this study, myocardial 18F-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 target recognition. 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 99mTc-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-fied apoptosis. 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 124I and 18F, is under way and may provide better avenues for coronary vascular imaging.

Conclusions 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. 18F-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 18F-FDG has evoked tremendous enthusiasm in the imaging community. Successful 18F-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.

References1. 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; 108:3134–3139.

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 99mTc-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 111In-IgG in 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-tion. 2002;105:2708–2711.

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 18F-fluorodeoxyglucose posi-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. 18Fluorodeoxyglucose positron emission to-mography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. J Am Coll Cardiol. 2007;50:892–896.

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 Cardiol. 2008;15:841–843.

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. 2007;116(suppl II):410.

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;46:2051–2056.

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. 99mTc-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 MeetingThe 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 wouldbe clinically useful in detecting cerebral amyloid, against what “standard of truth” should its perfor-mance be compared in phase 3 clinical studies?

• Whatarethestrengthsandweaknessesofthephase3 study designs presented by the three industry sponsors?

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 amyloid. 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, MDNational Institutes of Health

LitBriefsMI 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 in AtherosclerosisChen 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. 2007;104:961–966).www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19072768

“Quench and Chase” Strategy for Molecular ImagingOgawa 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 AngiogenesisAlmutairi 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 α

nβ

3 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 α

nβ

3

integrin receptors. …(19129498)

Color-Coded Fluorescent Protein Imaging of AngiogenesisAmoh 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. …(19128234)

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.

s Molecular imaging techniques

s Micro- and macro-PET/SPECT/Echo/MR/CT/Optical imaging

s Imaging probes

s Gene expression

s Receptors

s Inflammation

s Hypoxia

s Apoptosis

s Metabolism

s Atherosclerosis

s Angiogenesis

FeaturedTopics

Molecular Imaging

Symposium onMultimodality Cardiovascular

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 AdvancementThis 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

Meeting partners

Interested in sponsoring this dynamic meeting? Contact Marybeth Howlett at mhowlett@snm.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[3]: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 infarction. 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 decade. You can find more information about registration at www.snm.org/cvmi2009.

Albert J. Sinusas, MDYale University

Natcher Auditorium

National Institutes of Health

Bethesda Maryland

April 30- 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 atherosclerosis activitywww.auntminnie.com/index.asp?Sec=sup&Sub=mol&Pag=dis&ItemId=84627&d=1A 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. AuntMinnie.com

Researchers enhance PET/CT imaging with radiolabeled nanoparticleswww.nanowerk.com/news/newsid=9377.php Researchers used a chemical reaction called “click chemistry” to add the radioisotope 18F 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 agents. Nanowerk

Johns Hopkins to provide neuro-imaging hub www.healthimaging.com/index.php? option=com_articles&view=article&id=16214 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

Thefirstformalrevisionofspecificguidelines—ResponseEvaluationCriteriaInSolidTumors,orRECIST—usedbyclinicianstomeasuretumorsize 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. RECISTwerefirstpublishedin2000andareusedbyinvestigatorsinphase 2 and phase 3 clinical trials of new anti-cancer drugs as a way ofmeasuring the efficacy of the treatment. Tumor shrinkage (objectiveresponse) 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 mainendpointonwhichtobaseconclusionsabouttheefficacyofadrug. 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 and efficiently. 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 hpra@snm.org 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, PhDMICoE President-Elect

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-mative. 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 biosensors. “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 were amazing.” 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 molecularimaging@snm.org or 703-742-5498. You can learn more about the program at www.molecularimagingcenter.org.

mi gateway | 2009 7

SNM Speakers Bureau Brings Out the Best

New Criteria Will Ease Workloads in Clinical Trials

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

therapeutics.”

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

www.snm.org/clinicaltrials.

SNM Molecular Imaging Summit Introduces Clinical Trials Network

Multimodality Cardiovascular Molecular Imaging SymposiumApril 30–May 1, Bethesda, Md.www.snm.org/cvmi2009

American Society of Clinical Oncology May 29–June 2, Orlando, Fla.www.asco.org/ASCO/Meetings/ASCO+Annual+Meeting

Frontiers of Biomedical Imaging ScienceJune 2–5, Nashville, Tenn.www.vuiis.vanderbilt.edu/frontiers/

American Society of Echocardiography 20th Annual Scientific SessionsJune 6–10, Washington, D.C.www.asecho.org/i4a/pages/index.cfm?pageid=3278

SNM 56th Annual MeetingJune 13–17, Toronto, Ontario, Canadawww.snm.org/am

18th International Symposium on Radiopharmaceutical Sciences (ISRS)July 12–17, Edmonton, Alberta, Canadawww.isrs18.com/

Look for “Probe Development in Molecular Imaging and Therapy” at the ACS Fall 2008 MeetingAugust 16–20, Washington, D.C.oasys.acs.org/

World Molecular Imaging CongressSept 23–26, Montreal, Quebec, Canadawww.wmicmeeting.org

American Society of Nuclear CardiologyOct. 1–4, Minneapolis, Minn.www.asnc.org/

calendar

1850 Samuel Morse DriveReston, VA 20190P: 703.708.9000F: 703.708.9018www.molecularimagingcenter.org

MI Gateway is a quarterly member information service published under the direction of the Molecular Imaging Center of Excellence leadership and SNM.

©2009 SNM, Inc.

Editorial Board Carolyn J. Anderson, PhDOrest B. Boyko, MD, PhDPeter Herscovitch, MDH. Charles Manning, PhDTodd E. Peterson, PhDMartin G. Pomper, MD, PhDHenry F. VanBrocklin, PhD, Issue Editor

Board of DirectorsHenry F. VanBrocklin, PhD, PresidentCarolyn J. Anderson, PhD, Vice PresidentTodd E. Peterson, PhD, Secretary/TreasurerPeter S. Conti, MD, PhD, Board MemberHeather Jacene, MD, Board MemberJoel Karp, PhD, Board MemberMichael M. Graham, PhD, MD, Board MemberD. Scott Holbrook, BS, CNMT, Board MemberCraig S. Levin, PhD, Board MemberDavid A. Mankoff, MD, PhD, Board MemberJulie Sutcliffe, PhD, Board MemberJoseph C. Wu, MD, PhD, Board MemberLily Wu, MD, PhD, Board MemberMichael R. Zalutsky, PhD, Board MemberMartin G. Pomper, MD, PhD, Immediate Past President

SNM Chief Executive OfficerVirginia Pappas, CAE

Director of the MI Center of ExcellenceMarybeth Howlett, MEM

Managing EditorAnn Coleman

Production EditorKathryn Wiley

Graphic DesignerLaura Mahoney

Late-breaking News!March on Washington — Without Leaving Your Office!Join other SNM members for a virtual March on Washington. Launched to co-incide with Capitol Hill Day (see page 6), the Virtual March Web site lets you voice your opinions where it counts. Check it out at MIMarchforHealth.org

New Public Forums for Molecular ImagingDiscuss the molecular imaging issues that matter to you with colleagues from around the world. The MICoE’s new public forums were designed to give people working in molecular imaging a place to meet and discuss the topics they care about. Read the messages at www.snm.org/mi-forums or sign in to reply or start your own topic. Send feedback and requests for new forums to acoleman@snm.org.

Use Online Meeting Planner to Quickly Find Molecular Imaging Presentations at SNM’s 56th Annual MeetingNow you can browse the molecular imaging presentations planned for SNM’s Annual Meeting (June 13–17 in Toronto) using SNM’s Online Meet-ing Planner at www.snm.org/meetingplanner. Simply search using the term “molecular imaging” to see what’s on tap.