Visualize Man Molecularly - Molecular Imaging in Clinics.

The Molecular Imaging World Congress WMIC 2016 just concluded at New York last week. 

 Apart from our three presentations at the Congress, I was more excited with the outcome of a Scientific Session I moderated along with Thomas Helbich - "First-in-Man & Clinical Studies in Oncology" Moderator(s): Thomas Helbich (Austria)and Rao Papineni (USA).

Undoubtedly, the scope of Molecular Imaging in clinics remains untapped, yet!  This after a good decade of the hype and hysteria. My take here is that there are quite a number of gate-keepers and fair weather stake holders outside of the Molecular Imaging field that is shaping the entry into clinical arena - which is partly good, for the caution taken, while mostly frustrating for a hardcore researcher.

Four years ago, Sam Gambhir of Stanford concluded in his review (2012) with the following note; "To expedite clinical translation of promising imaging agents and instruments, we need to prove its clinical utility. This should be accomplished by increasing the number of rapid first-in-man efforts and by demonstrating safety and reproducibility through standardization of techniques. Academic groups developing imaging agents need to collaborate with each other to accelerate clinical translation and to perform multicenter international clinical trials. Novel models that involve academia, industry (pharmaceutical and imaging companies), governments, and foundations need to be better explored. Without help from industry, academic groups will never be able to bring enough molecular imaging agents into pilot trials. Intellectual property issues related to novel imaging agents also need to be considered along with business models to show profitability for specific imaging agents and their clinical applications" (Phys Rev 2012).

Key Steps Involved in Molecular Imaging- Bench to Clinics

Readers who would like to know about the path assigned for Molecular Imaging to enter Clinics, the following schema from the above Physiological Review issue will be informative.  For general public, Molecular Imaging (MI) is a broad field  that encompasses and not just limited to a range of image technologies allowing  physicians, surgeons, and researchers to noninvasively visualize physiological processes at a cell and molecular level.
Radiation Therapy and Radiation Research are fields rapidly encompassing MI at different levels.  Here, I feel elated to state that my lab made the early attempts integrating MI in the Radiation Research Field (ICRR Poland 2011). The scope in MI- Radiation Therapy is phenomenal and anticipated to be profound, especially with the advances in radiobiophotonics -  Radiobioluminescence, cerenkov luminescence-God light in likes, a potential in radiation therapy imaging (http://www.cancerjournal.net/text.asp?2015/11/1/241/155113 )

Back to the blog, the researchers who presented in the Scientific Session we chaired at WMIC 2016 were from across the globe -  Singapore, Denmark, USA, and different parts of Northern Europe.  Although mostly proof-of-concept studies, the outcome were indeed promising.  The talk that raised eyebrows include the application of uPAR gallium radioligand tagged peptide, showing the potential to circumvent invasive sentinel node surgeries in breast cancer patients.  With 1 in 8 women developing invasive Breast Cancer - such MI based breakthroughs will be extraordinary during operative procedures with lumpectomy or mastectomy.

Other noteworthy presentations ranged from utilization of optoacoustics, magnetic nanotechnology, fluorescence endoscopy; determination of the lesion dimensions of non-melanoma carcinomas during surgical removal; surveillance endoscopy in Barett esophagus were evaluated and deliberated.

Overall, these Pilot programs across the world are steps in the right direction for Molecular Imaging to reach the pinnacle and contribute to the betterment of human health.  It is however imperative;  Radiologists, Surgeons, Pathologists, radiation Oncologists, Academic & Industry Researchers, Health Agencies, Government Regulatory Bodies, Computational Wizards, and Technologists have to interact and collaborate more stringently for the MI benefits to acquire the Moonshot Moment towards clinics and personalized Medicine.

Papineni Labs are Biomedical Research Labs in Honor of my Father Mr. Papineni Venkateswara Rao.

 

 

http://www.radres.org/blogpost/961725/250704/Cancer-Therapy--Radiobiophotonics-with-Rao-Papineni
 
"Molecular Imaging - Wisdom to See for Maladies to Flee"
                                                          Dr. Rao V. L. Papineni

Dr. Rao Papineni to Join at World Molecular Imaging Congress WMIC 2016.

  
                                       

Dr. Rao Papineni will be traveling to New York to attend the 2016 World Molecular Imaging Congress (WMIC 2016). The WMIC is organized by the World Molecular Imaging Society (WMIS) and provides a unique platform for scientists and clinicians to present and follow cutting-edge advances in molecular imaging. The theme of WMIC 2016 is Imaging Biology...Improving Therapy.

Dr. Rao V. L. Papineni will serve as chairperson at the First-in-Man & Clinical Studies in Oncology session on Friday, Sept. 9.

He will also present three research presentations:

1. Brown Adipose Tissue activity in Cancer and treatment - A Clinical Evaluation.

2. Stress Visualization in Gastrointestinal Tract at Different diseases Forwards a Systems Approach to Drug Repurposing

3. Generation of Cardiac Precursor Nanoprobe and Image Guided Biodistribution Analysis.

These projects have been a collaborative effort between Apollo Hospitals, Abertay University, Defense Research and Development Organization (DRDO), Global Hospitals, University of Kansas Medical Center (KUMC), Oklahoma Medical Research Facility (OMRF),  Precision X-Ray Inc PXi and PACT & Health LLC.

WMIC 2016 will be held at the Jacob K. Javits Convention Center located at 655 West 34^th Street in New York.

A glimpse at the Current Research Initiatives of  Papineni Labs in the following Podcast.
https://www.youtube.com/watch?v=SbWhUvfmwRY


Please contact  Dr. Papineni at Papineni@Graduate.HKU.HK  or Docpapineni@gmail.com

Abstracts of the Presentations:
TITLE: Brown Adipose Tissue activity in Cancer and treatment - A clinical evaluation

AUTHORS (FIRST NAME, LAST NAME): Rao V. Papineni1, Jyotsna Rao2, Achyut R. vyakaranam2

ABSTRACT BODY: Abstract Body: Brown adipose tissue (BAT) acts as a thermogenic organ producing heat to maintain body temperature, particularly in the young. The locale of BAT is generally in deep cervical, supraclavicular, interscapular, and paravertebral regions, as well as areas near large vessels. BAT activity routinely interferes with 18F-FDG (fluorodeoxyglucose) Positron emission tomography (PET)/computed tomography (CT) image interpretation. Visualization of Brown adipose tissue (BAT) in children is speculated to depend on disease status, weight, body composition, and degree of sexual development. A retrospective analysis of the pediatric patients 18F-FDG PET/CT scans is in progress to assess the BAT activity during cancer and post chemo or radiotherapy. Our early findings presented here show the feasibility of visualization and scaling of the BAT activity in pediatric cancer patients, and the change in BAT activity upon treatment. As expected, the lymphoma cases are distinctive in terms of the BAT activity. A case report of a male 16-year-old patient is presented - patient diagnosed with lymphoma showed supra diaphragmatic disease with no metabolic brown fat activity. After chemotherapy, the subject’s scan showed prominent brown fat activity in the neck. The result is in agreement with the assumptions that patients with malignant lymphomas have high levels of tumor necrosis factor alpha, a cytokine capable of inducing apoptotic degeneration of brown adipocytes. The variation in BAT activity during neuroblastoma treatment are shown. This retrospective pediatric patient study is in progress and will provide an in-depth view of BAT as a diseased state predictor during cancer, chemotherapy and radiotherapy.

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Lymphoma- 16 Yrs Partient Pre Treatment- No BAT activity

IMAGE CAPTION: Lymphoma- 16 Yrs Partient Pre Treatment- No BAT activity

CONTROL ID: 2501225

TITLE: Stress Visualisation in Gastrointestinal Tract at Different diseases Forwards a Systems Approach to Drug Repurposing

AUTHORS (FIRST NAME, LAST NAME): Rao V. Papineni1, Shahid Umar2, Alexey Goltsov3, James Bown3, Ishfaq Ahmed2

ABSTRACT BODY: Abstract Body: Akin to Hippocrates’s quote “All disease begins in the gut”, carcinogenesis, bacterial infection, mechanically induced inflammation, and X-Ray radiation toxicity present similar pathological response at the GI. The similar genotoxic stress response of GI microenvironment to different pathologies suggests a link between inflammatory/immunity and cancerogenesis. The chemiluminescence ROS activity measured under different pathological conditions show a robust increase in the gastrointestinal tract region during radiation injuries, Citrobacter rodentium intestinal infection, and in ovarian metastasis mouse cancer model. ROS activity determination performed through non-invasive in vivo imaging was facilitated using a sensitive cooled CCD camera and a chemiluminescence molecular probe. The host’s inflammatory response in terms of direct formation of ROS and subsequent oxidative stress is similar to GI injury resulting either from whole body X-ray irradiation or following infection with an enteric pathogen. This marked resemblance can be similarly extended to other pathophysiological conditions. Systems biology approach is developed to investigate a role of ROS and pro-inflammatory cytokine signalling in crosstalk and communication among different cells making up a chronically inflamed tumor microenvironment (GI epithelial, cancerous, stem cells, and macrophages) and to model molecular mechanisms underlying cancer progression, invasion, host immune modulation, and the development of cancer therapeutic resistance. These systems biology integrative approaches presented provide understanding of how the complex GI microenvironment of cell populations interacts, communicates and forms integrated responses to pathogens and diseases. Such analysis provides opportunities in the design of effective treatment strategies and preventive countermeasures against acute GI damage induced by chronic inflammation and GI injury as a result of radiotherapy. Further, novel strategies in personalized cancer therapy can be developed on the basis of repurposing drugs that modulate different cell populations and suppress tumor progression through inhibition of immunosuppressive, pro-angiogenic, and tissue remodeling factor release in the tumor microenvironment.

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Inflammation response of GI tract cells to bacterial pathogen and cell cross talk via Reactive Oxygen Species ROS signalling

IMAGE CAPTION: Inflammation response of GI tract cells to bacterial pathogen and cell cross talk via Reactive Oxygen Species ROS signalling

CONTROL ID: 2501207

TITLE: Generation of cardiac precursor nanoprobe and image guided biodistribution analysis.

AUTHORS (FIRST NAME, LAST NAME): Rao V. Papineni2, Rheal Towner1, Partha Ghosal3, Lakshmi Chelluri4

ABSTRACT BODY: Abstract Body: In order for cell based therapy to truly succeed, it is imperative to track the locations of the delivered cells, the duration of cell survival, and any potential of adverse effects. Analysis elsewhere, on the stem cell therapy using bio-luminescence imaging indicates that about 90% cell death within first 3 week of delivery due to harsh microenvironment leading to short-term improvement of cardiac function. This may limit the overall efficacy of stem cell based therapy. The nanoparticles in cancer theragnostics and for stem cell tracking, as a rule of thumb should differ in the amounts of chemistries involved in preparation. We earlier developed a multimodal nanoparticle (NP) that can be simultaneously be imaged by near -IR, and magnetic resonance Imaging (MRI) modalities to avail the best of the spatial resolution, sensitivity, and the depth detection. Here, a multimodal cardiac precursor nanoprobe fabricated using minimal chemistries for non-invasive molecular magnetic resonance (MR) imaging and cell based myocardial repair is developed and evaluated. Herein, the modified approach which is economical, scalable and potent prototype of a cardiac precursor nanoprobe that functions as a cell label and tracking agent is presented. This probe constitutes cardiac specific antibodies against SIRPA and KDR that are bound to the surface of PEG coated SPION which aids in the segregation of cardiac precursor cells from cardiac/non cardiac origin for cellular therapy. Characterization of the size (TEM, SEM, Zetasizer), topology (AFM) and surface charge (Zeta potential) along with the in vivo biodistribution through MRI are presented. The results from this study show these nanoparticles (GloTrack) as a negatively charged, 900 nm size on an average with a uniform distribution of cardiac specific antibodies. The feasibility of its tracking in vivo using MRI is confirmed by non-invasive imaging of the kinetic bio distribution of the nanoparticles in C57BL6 mice through a series of images over 90 min period. These nanoparticles capable of minimizing ex-vivo cell manipulation, potentially allows real-time visualization of cardiac precursor cell delivery, homing, proliferation and regeneration.

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MR imaging of in vivo biodistribution of Cardiac nanoprobe-GloTrack in C57BL6 mice. (i) T2 –weighted pre-contrast MR images (i.e) pre-injection of GloTrack (ii) T2-weighted post contrast (post-injection of GloTrack) image after 90 min. (iii) Difference image, i.e “ii minus i” in (a) Mouseheart [h] and (b) heart, liver [lv] and kidney [k].

IMAGE CAPTION: MR imaging of in vivo biodistribution of Cardiac nanoprobe-GloTrack in C57BL6 mice. (i) T2 –weighted pre-contrast MR images (i.e) pre-injection of GloTrack (ii) T2-weighted post contrast (post-injection of GloTrack) image after 90 min. (iii) Difference image, i.e “ii minus i” in (a) Mouseheart [h] and (b) heart, liver [lv] and kidney [k].

Papineni Labs are Biomedical Research Labs in Honor of Mr. Papineni Venkateswara Rao.