AMI & SMI Joint Molecular Imaging Conference and Pre-conference Symposium

Providence Convention Center and Travel Award list

My Poster and Water-fire display

I attended the AMI/RSNA/SNM/SMI clinical pre-conference symposium and Joint molecular imaging conference held at Providence, Rhode Island in USA from September 7-11, 2007. This was my third successive time to attend the molecular imaging conference. Unlike the previous years, in which the Society for Molecular Imaging (SMI) organized the event, this year a joint conference was held following the merging of SMI and Academy of Molecular Imaging (AMI). The conference venue of Providence was an aesthetically pleasing locale for the big event.
The pre-conference symposium was held on Sept 7th and 8th consisting of various categories to educate the clinicians and researchers about fundamental aspects and utilities of various imaging modalities. I had registered for ‘Molecular Imaging Fundamentals in Medicine’ which covered wide ranging topics such as molecular biology, nanotechnology, optical imaging, neurological, cardiovascular, stem cell and cancer imaging strategies. The use of microarray for determining gene expression patterns in neurological diseases such as multiple sclerosis, schizophrenia and Alzheimer’s disease or physiological conditions such as aging and learning was reported. However, the requirement of biopsy and low spatial resolution limits were presented as impediments for the technology to enter clinical practice. The presentation on nanotechnology focused on various issues to be dealt before in vivo application and addressed the need for achieving signal amplification by conjugation strategies and development of multi-functional or multi-modal nanoparticle agents. Various optical imaging strategies were discussed based on protease or cathepsin B over-expression and integrin targeting using RGD peptide conjugated fluorescent probes for intra-operative imaging. Another upcoming optical imaging approach called Photoacoustic imaging was elaborated, which notably has high resolution and can reach a depth of ~5 cm with NIR excitation and ICG contrast. In the recent developments in ultrasound molecular imaging, a possibility of real time imaging using multifrequency transducers and Fluorine-18 labeled microbubbles capable of generating both ultrasound and nuclear contrast were reported. A study from MGH reported about an optical imaging probe called Prosense Molecular Imaging probe (NIR Fluorochrome activated by disease associated cysteine protease) which is being validated for ovarian tumor detection and is already in Phase 1 clinical trial.
This year there were over 980 abstracts selected for the Joint Molecular Imaging Conference meeting, with ‘Cancer detection imaging’ topping at 151, followed by 73 on ‘Quantitation in molecular imaging’ and varied numbers in other categories. The meeting started with a keynote lecture from Sir George Radda of University of Oxford. He began his talk with mechanisms governing homeostasis and mentioned about the four key elements in cellular dynamics – energetics control, ionic fluxes, signal transduction and gene expression. He stressed the importance of integrative approach to human disease involving characterization of changes in molecular events in an individual subject (i.e. taking personalized medicine to molecular level). Majority of talk focused on various biochemical events such as mitochondrial energy coupling, myocardial triglyceride content detection by MRS, PPAR activation and so on, that are being targeted for molecular imaging.
From the next day, the plenary and concurrent sessions were held with poster sessions in the evenings of each day. Some of the interesting presentations can be grouped as per the educational objectives defined by the Molecular Imaging committee.

• Explain methods of target identification and probe development for disease targets. The ultrasound contrast agents in the form of microbubbles were used by many groups specifically targeting VEGF receptor (to detect angiogenesis in tumors), integrins (to detect αvβ3 expression) and selectins (to study dynamic selectin activity in vivo). In a study targeting ErbB-2 receptors the researchers developed a phage display selected peptide, and showed specific binding to ErbB-2 expressing tumor cell lines both in vitro and in vivo.
  
• Describe effective approaches to cancer and cardiac disease detection and outcome measures. The development of high resolution PET applicable for cardiovascular molecular imaging was reported which contains high density avalanche cathode detector yielding a submillimeter resolution with respiratory and cardiac gating recorded in list mode data. The group from Stanford reported on usage of ultra high sensitivity and multiplexing characteristics of Raman spectroscopy into a new preclinical imaging device for non-invasive cancer imaging. They incorporated Raman-active nanoparticles (single walled nanotubes, SWNTs) conjugated with RGD peptide to localize αvβ3 expressing tumors in nude mice and imaged using optimized Raman microscope.
  
• Evaluate the potential of new imaging methods to detect disease early in its course and recognize when there is the potential for improved outcome. The advantage of using multi-photon microscopy was demonstrated in which due to higher depth penetration, quantitative functional analysis of skeletal muscle with 3D structural depiction or visualization of LDL deposition between collagen and elastin layers of vessel wall was feasible. A new method of generating B1 contrast using micro-resonant devices (MRDs), which are basically micron-sized solid-state devices, was reported to provide high sensitivity 3D localization using 3T MRI. A novel MR-based PET attenuataion correction was presented where in researchers proposed using a combination of atlas-registration and local pattern recognition to predict a pseudo-CT image. They also validated an approach that can quantify PET images with an error that is smaller than what is clinically significant.
  
• Describe the new imaging paradigms in drug discovery and development. The importance of parallel analysis technologies so as to introduce an ‘exploratory’ phase in drug development was noted. Broad-based methods such as microarrays or proteomic approaches for pharmacodynamics and stratification in early drug development was recommended.
  
• Recommend imaging and therapy combinations. A research group from MGH/Harvard medical school presented in vivo imaging of siRNA delivery and silencing in tumors. To achieve this, they developed a dual-purpose probe called MN-NIRF-siSurvivin that enables both tumor delivery and imaging by MRI. Using that probe, they reported significant silencing of the tumor-specific, anti-apoptotic gene birc5 (encoding Survivin) and also capability to monitor tumor regression by MRI and NIRF imaging.


• Appraise the role of molecular imaging in cellular, stem cell, and gene therapies. In order to quantify endothelial binding of targeted radioactive liposomes, a research group from University of California presented an approach incorporating heart-homing peptides onto the liposome surface which also consists of [18F]fluorodipalmitin ([18F]FDP) radioactive lipid. The accumulation of liposomes in the heart muscle was up to 60% ID/g and averaging several fold higher than in liver, lung or skeletal muscle. An optical reporter based strategy was presented to facilitate real-time monitoring of post-translational stabilization of β-catenin, a key signaling component of the canonical Wnt pathway. This system was proposed to be useful to determine pharmacodynamic and pharmacokinetic profiles of drug candidates.

Apart from presentations, there were few posters which were informative and educative. My poster was under the category of “Imaging gene expression” and I had some thoughtful discussions with various researchers on utility and development of my adenoviral reporter gene system. I am glad to recieve this year's student travel award for my abstract. Besides the educative presentations, the organizers had arranged for cultural extravaganza of Providence which included water-fire display on the Providence river. The next year's meeting is announced as World Molecular Imaging Congress to be held in Nice, France. With the society growing big and getting more and more international participants including from Asia, I wonder the prospects of the meeting happening in Asia, and particularly in Japan.

JSMI 2007 Conference at Fukui, Japan

I attended the 2nd Annual conference of Japanese Society for Molecular Imaging held on 28th and 29th June 2007 at Fukui, Japan. This was the second time a major conference was held here at Fukui, my present city of abode. We were the organizers cum hosts of this meeting and my chief supervisor Prof. Fujibayashi is the president of the society.

Though this society is still in infancy celebrating its first anniversary this year, the growth and interest were felt overwhelming among the researchers. The first day morning comprised of symposium sessions from the eminent speakers of US and Europe. The opening keynote lecture by Dr. Jurie Gelovani (University of Texas, MD Anderson Cancer center) was on ‘molecular-genetic imaging in cancer diagnosis and therapy’. He stressed on the importance of developing effective strategies to image tumor biomarkers in facilitating early and accurate diagnosis. Imaging can not only play a major role in tumor profiling but also in therapy assessment in terms of dose, duration and tumor prognosis. He also presented the evaluation of fluoroacetate-PET in multitumor model conducted in rats and EGFR expression by PET imaging. The recent research progress on imaging the activity of HDAC (using Fluorine-18 labeled FAHA) in tumors was quite interesting. The dynamic biodistribution of PET radiotracer over the entire duration of emission scan was highly impressive. Progress in myocardial stem cell implant and imaging by HSV-tk expression was also mentioned. His forecast for the future imaging strategies included multiple radiotracers for imaging tumor-specific tissue biomarkers (‘imageable biomarkers’), development of more C-11 tracers, more sensitive PET systems with longer Z-axis and use of PET/MRI or PET/CT+MRI imaging systems.

The title of next speaker Dr. Timothy J McCarthy (from Pfizer R&D) was ‘Imaging as a key enabling tool in drug development’. He emphasized particularly on how molecular imaging plays a key role in new drug development and evaluation. Few examples given were discovery and validation of a PET tracer for the 5-HT1B-receptor, F-18 labeled galacto-RGD tracer evaluation for tumor imaging, checkpoint kinase inhibition by FLT, development and evaluation of sutent in tumor treatment and MR image contrast mechanisms (imaging methemoglobin) in various diseases. He also highlighted about the importance of upcoming Joint Molecular Imaging Conference in this year and emphasized that partnerships at all levels are critical to the future of molecular imaging.

The third speaker was Dr. Hisataka Kobayashi (National Cancer Institute, NIH), who spoke on ‘Multiplexed in vivo cancer imaging’. Initially he described the current status of molecular imaging in NIH (USA). Molecular Imaging forms one of the five NCI 2015 core projects (others are Genomic, Proteomic, Molecular targeting and Nanotechnology). He also mentioned salient features from Dr. Zerhouni’s lecture on ‘Bioscience in 21st century’ from NIBIB’s fifth anniversary symposium. His talk focused on multi-parametric imaging where in multi-color probes, activatable “smart” agents and multi-modal agents can be utilized. Using 2-color fluorescent probes, both time and spectrally resolved dynamic image can be simultaneously obtained. Use of pH sensitive probes (activatable GSA-BDP) enabling targeted tumor imaging even in the presence of ascites was well demonstrated.

The next talk by Dr. J.L. Coll (University of Grenoble, France) was on molecular imaging in the European community specifically focused on optical imaging strategies for detection, medical imaging and cancer treatment. He described the attributes of regioselectively addressable functionalized template (RAFT) presenting four cyclic RGD peptides linked to Cy5 (a fluorescence quencher) as an effective probe for imaging tumors and in vivo RGD-mediated internalization. He also highlighted the utility of 2D-fluorescence reflectance imaging (FRI) and 3D imaging in vivo using fluorescence diffuse optical tomography (FDOT).

The evening plenary talk was delivered by Dr. Roderic I Pettigrew (Director, NIBIB). He stressed the future of molecular medicine depends on developments occurring in three core fields – genomics, nanotechnology and bioimaging systems analysis. Current molecular imaging technologies can detect molecular complexes, proteins, enzymes and even gene expression but little it can do in delineating intracellular molecular movement, transient assemblies and temporal-spatial relationships. Few interesting research findings discussed were – use of molecular beacons to view tadpole “tail” mRNA migration, multi-isotope mass spectrometry imaging which provides high resolution imaging of protein metabolism, control of sweet preference in transgenic mice at the level of sweet taste receptors, photonic crystal tear glucose sensing, MR guided optical fluorescence measurement and so on. Probe sensitivity needs to be amplified to label individual molecules or detect individual molecular events in single cells and in the order of 1000-fold to that of original signal. He also highlighted that the future research perspective should aim at focusing on system of targets (not a target) and understanding disease pathways in terms of fundamental disease mechanisms such as inflammation, protein action, apoptosis or cell signaling. There is also a need for more precise, quantitative and accessible new research tools such as animal models, novel probes, preclinical biomarkers and targeted delivery systems.

In the evening banquet ceremony, I was surprised and elated to know that my poster was awarded as one of the three best posters in the current meeting. It was a glorious moment worth cherishing for a long time to come when I received the award by none other than my chief supervisor, Prof. Fujibayashi.

In the next day , there were some interesting presentations from eminent Japanese researchers. Dr. Okano Hideyuki of Keio University presented “Imaging techniques in regenerative medicine”, where in he discussed the mechanisms of regeneration of neurons by neuroblast activation. Visualization of CSF flow can be facilitated by using 7.4 Tesla MRI and Mn2+ ion. Visualization of CNS tracts in the intact cervical spinal cord of marmosets using diffusion tensor tractography was also demonstrated which could be applicable to real time evaluation of axonal degeneration. The use of bioluminescence imaging for quantitative assessment of estrogen dependent growth was also discussed.

Dr Takahiro Ochiya of National Cancer Research Institute delivered lecture on “imaging molecular targets for cancer therapy” where in he elaboratively described interference (RNAi), siRNA/atelocollagen complex and various microRNA (miRNA) groups currently discovered as molecular targets for cancer therapy.

The talk by Dr Eiji Kobayashi of Jichi medical university was titled “In vivo imaging using dual colored Tg rats for innovative medical research”. His group have developed various colored Tg rats (of different fluorescence or luminescence) using transgenic technology. Many other oral sessions were also stimulating but couldn’t comprehend completely due to language barrier. Overall, the 2nd JSMI meeting was a successful outcome especially with our group being the hosts of the big event.

SNMI 2006 conference at Jamshedpur, India

I attended the 38th annual conference of Society of Nuclear Medicine, India (SNMI) 2006 held from 13-16th December at Jamshedpur, in Jharkand, a northern state of India. Jamshedpur is well known as “Steel city of India” and the home of Tata conglomerates, popular worldwide for Tata steel, Tata motors, Tata Tea and many others. The conference was organized by Nuclear Medicine Department of Tata Main Hospital.

The theme of the conference was chosen to be “Basics….& the Best” to refresh basic principles governing nuclear medicine and highlight recent advances available to the medical fraternity.

The Scientific Programme started with the CME sessions on day 1 and followed by conference sessions for 3 days, which included orations, panel discussions, free papers and read-with-experts sessions. There were nearly 250 delegates including students, with experts coming from USA, UK and Brazil. Dr. Tiwari and I were the only representatives from Japan. There were 38 oral presentations in free paper sessions and 21 poster presentations.

The CME sessions covered recent technological advances in nuclear medicine, nuclear cardiology, brain tumors, pulmonary embolism, hepatobiliary imaging and renal hypertension. The talks were given by experts from both India and abroad. Dr. Sharmila Banerjee discussed about an indigenously produced 125I-sources for ocular or prostate cancer therapy. In the PET-CT section, Response evaluation criteria in solid tumors (RECIST) was highlighted. Dr. Dominique Delbeke, visiting faculty from USA gave a talk on current concepts of SPECT v/s PET v/s coronary CTA for applications in Nuclear cardiology. The significance of various established SPECT and PET tracers and the role of coronary calcium scoring were thoroughly elaborated. Dr. C.S. Bal of AIIMS delivered a lecture on Functional / Metabolic imaging in brain tumors where in he elucidated the availability of different clinical tracers for detection and staging of differential grade brain tumors. Dr. Harsh Mahajan of Mahajan Imaging Centers delivered lecture on usage of CT / MRI in evaluation of brain tumors with special emphasis on ultra-fast sequences, Diffusion tensor imaging (DTI) and MR tractography. Dr. BA Krishna of Hinduja Hospital highlighted the different hepatobiliary disorders that could be evaluated by HIDA scan.

The Homi Bhabha oration on 14th December was given by Dr. Anil Kakodkar, chairman of Atomic Energy Commission. He is a key figure in development of Nuclear energy in India. He commended the expanding application in peaceful uses of nuclear energy. Dr. Delbeke gave an elaborative talk on integrated FDG-PET and PET/CT for assessment of tumor biology where in she covered a range of tumors that can be structurally and functionally evaluated by latest imaging modality, the PET/CT. Her next talk focused on the application of FDG-PET and other tracers in infection and inflammatory diseases. Novel tracers like 67Ga-citrate, 111In and 99mTc labeled WBCs, labeled human Ig, antigranulocyte antibody and peptides were all mentioned for diagnosis and management of infections such as osteomyelitis, diabetic foot, HIV, FUO, arteritis, thrombophlebitis, acute pancreatitis and so on. In the evening, a quiz on nuclear medicine was held where in five teams each of 3-4 members participated. I along with Dr. Tiwari and Dr. Ponraj (junior from IIT Kharagpur) formed a team and were able to win runners-up prize.

The next day started with free paper session, where in Dr. Tiwari`s presentation was also scheduled. Most of the presenters were from India and elaborated their respective research works. Few interesting papers presented were the use of radiolabeled stem cells, preparation of 99Mo-99mTc generators and biodistribution studies of radiolabeled biotin vs gammaglobulin. My talk was scheduled for post lunch session under PET category. With the limited audience, there were not many questions raised for my presentation.

The final day had interesting presentation for Vikram Sarabhai oration from Dr. John Buscombe, a visiting faculty from UK. He briefed on radionuclide therapy such as Y-90 labeled tiuxetan ibrutumab for NHL, In-111 labeled Zevalin for follicular lymhoma, Radium-223 therapy for bone tumors and so on. Surprisingly in the valedictory function, mine and Dr. Tiwari`s names were announced to receive the awards for second-best presentations in our respective categories.

The enlightening academic sessions were followed each day by the evening cultural amusements of light music and drama.Finally, my perspective from the meeting is that a gradual but steady progress is ongoing in terms of PET and clinical nuclear medicine research with most of the major cities having hybrid PET/CT scanners. In near future, new installations of cyclotrons will likely happen and more number of nuclear medicine centers will actively participate to further advance this emerging field in medicine.