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Publications
Dr. Mathew Thakur


I am a professor of Radiology and Radiation Oncology at Thomas Jefferson University in Philadelphia. I am also the Director of the laboratories of Radiopharmaceutical research and Molecular Imaging. I obtained my MS and PhD degrees from the University London, England. The major thrust of my research is to develop radiopharmaceuticals for diagnostic and therapeutic applications. I hold 20 granted patents and serve on the editorial board for 14 journals.

My contributions to the field of nuclear medicine and molecular imaging is well recognized by my peers, for which I have received 9 national and International awards, including the Society of Nuclear Medicine’s highest honor, the Benedict Cassen award. I have been elected as President of three international societies, including the Society of Nuclear Medicine and Molecular Imaging. I have been fortunate to have had four of my compounds commercialized and preparations are on the way for two more to be taken into clinical trials.

 

 

Dr. Leonard Gomella


Dr. Leonard Gomella is the Bernard W. Godwin, Jr. Professor of Prostate Cancer and Chairman of the Department of Urology at Jefferson Medical College. Originally from New York, Dr. Gomella completed medical school, general surgery and urology training at the University of Kentucky in Lexington, Kentucky. After a Urologic Oncology Fellowship in the Surgery Branch of the National Cancer Institute in Bethesda, Maryland, he joined the faculty of Jefferson Medical College in 1988 and was appointed Chair in 2002. He is also Associate Director for Clinical Affairs for the Kimmel Cancer at Jefferson and Urology Chair for RTOG, serving as lead Urology investigator on multiple national trials. In 2008 he was named Clinical Director of the Jefferson Kimmel Cancer Center Network.

Dr. Gomella is involved in both basic science and clinical research in the development of new diagnostic techniques and treatments for prostate, bladder and kidney cancer through Jefferson’s Kimmel Cancer Center. Dr. Gomella’s team was first to use RT-PCR to detect micro metastasis in patients with prostate cancer, a discovery that led to a new field of investigation in this disease. Dr. Gomella is also recognized as an early contributor to urologic laparoscopy, initiating the program at Jefferson in 1990.

NuView Life Science Commitment to Cancer Diagnostics and Treatment

The major thrust of our research was to develop specific peptides that will target biomarkers for early and accurate diagnosis of cancer, and then utilize as a precision therapy delivery vehicle for treatment resulting in saving patients’ lives with improved quality of life and lowering healthcare costs.

Biomarkers are a hallmark of many cancers. VPAC1 biomarkers, for example, are expressed on cell surfaces in high densities at the onset of oncogenesis. When VPAC1 receptors are targeted, cancer can be diagnosed early, but specifically, allowing physicians to distinguish malignant to benign lesions. This can lead to minimizing the number of unnecessary biopsies currently required to obtain a tissue for histology, which can induce anxiety in patients and cost billions of healthcare dollars.

There is a compelling need for a new precision technology that will distinguish malignant from benign lesions noninvasively in three areas of cancer care. VPAC1 cancer over expressions can account for: (1) Urine or Body Fluid In-Vitro Liquid Biopsy (2) Blood Based In-Vivo Radionuclide Imaging and (3) Blood Based Target Specific Radiation Therapy.

A recent Thomas Jefferson University validation study has been performed to confirm the binding accuracy to shed cancer cells in voided in urine. The study realized over 95+% sensitivity and 90% specificity confirming the presence of cancer cells **. The same peptide tagged with a radionuclide is being utilized as a diagnostic imaging agent with positron emission tomography imaging procedures. Thomas Jefferson University has already performed clinical development in patients to confirm (40) breast and (40) prostate cancers with highly accurate end points.  Utilizing 64Cu-TP3805 which promises to be an effective imaging agent and utilizing 67Cu or a preferred chemo drug for precison therapy. 64Cu & 67Cu-TP3805, target VPAC1 oncogene receptors, unequivocally detecting and treating all malignant lesions by PET/CT and PEM and all involved lymph nodes.

Cancer remains a formidable disease of mankind. Despite the striking advances made over the past few decades in the management of cancer, the disease kills 4 individuals in the United States and 15 individuals in the world every minute, 24 hours a day, and 7 days a week. Early and accurate detection and precision therapeutic delivery saves lives.

 

**Two different observations – with an in vivo imaging test you have perhaps 100% specificity because you can see which organ is upregulating the VPAC receptor as it’s in the picture, however looking on a slide in vitro and just at random cells blooming that isn’t very specific and why you need to do a cell confirmation test.

This publication will validate the Thomas Jefferson University hypothesis that prostate cancer can be detected non-invasively by a simple and reliable assay by targeting genomic VPAC receptors expressed on malignant prostate cancer cells shed in voided urine.

Development of a voided urine assay for detecting prostate cancer non-invasively

Edouard J. Trabulsi*, Sushil K. Tripathi†, Leonard Gomella*‡, Charalambos Solomides§, Eric Wickstrom‡¶ and Mathew L. Thakur†‡ Departments of *Urology, The Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.

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This publication will show VIP receptors are very important in the biology of many malignancies and are overexpressed in many tumors; thus, VIP receptors can be targeted by receptor-specific molecules. The generation of radiolabeled peptides has opened new avenues for the molecular imaging and therapy of tumors. They are becoming ideal candidates for molecular imaging techniques and therapeutic interventions.

   Vasoactive intestinal peptide receptor-based imaging and treatment of tumors (Review)

1Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037; 2Department of Nuclear Medicine,

Referenced: Thakur ML, Marcus CS, Saeed S, Pallela V, Minami C, Diggles L, Le Pham H, Ahdoot R and Kalinowski EA: 99mTclabeled vasoactive intestinal peptide analog for rapid localization of tumors in humans

Thakur ML, Chakder S and Rattan S: 99mTc-labeled vasoactive intestinal peptide receptor agonist: functional studies.

Thakur ML, Marcus CS, Saeed S, Pallela V, Minami C, Diggles L, Pham HL, Ahdoot R, Kalinowski EA and Moody T: Imaging tumors in human

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The Laboratories of Radiopharmaceutical Research and Molecular Imaging at Thomas Jefferson University have previously shown that 64Cu-TP3805 can specifically target VPAC1 receptors and can be used for positron emission tomography (PET) imaging of breast (BC) and prostate cancer (PC) in humans.

Availability of ready to use N2S2-peptide kits for 64Cu labeling is convenient and eliminates possible day to day variation during its routine preparation for clinical use.

Authors: Sushil K Tripathi, Pardeep Kumar, Edouard J Trabulsi, Sung Kim, Peter A McCue, Charles Intenzo, Adam Berger, Leonard Gomella, Mathew L Thakur Nucl Med Biol 2017 Aug 3;51:55-61. Epub 2017 May 3. Thomas Jefferson University, Department of Radiology; The Sidney Kimmel Cancer Center. Electronic address: August 2017

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In recent years, imaging tumors with receptor-specific biomolecules has been the focus of increasing interest. Vasoactive intestinal peptide (VIP)(VPAC) has a high affinity for specific receptors that are expressed in high density on many malignant tumors.

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This feasibility study will demonstrate the compelling need for an innovative approach that would decrease the number of unnecessary benign biopsies while still detecting the malignancies. A high percentage of the breast biopsies that were performed in the United States have resulted in a benign diagnosis. These unnecessary biopsies create significant patient morbidity and potentially unnecessary health care costs. To detect BC, digital mammography, MRI, CT, sonography, 18F-FDG, and 99mTc-sestamibi have made significant advances. However, these modalities have limited specificity, and all continue to produce many false-positive and false-negative results (3–12). At an average cost of $5,000–$6,000 for each biopsy, unnecessary benign biopsies represent a serious health care burden.

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The feasibility study of 25 patients who underwent PET imaging, 212 prostate gland lesions had SUVmax > 1.0 vs 127 lesions identified by histology of biopsy tissues. The status of the additional 85 PET identified prostate lesions remains to be determined. In 68 histologic slides from 6 PET imaged patients, DAR (Digital Autoradiography) identified 105 of 107 PC foci, 19 of 19 high-grade prostatic intraepithelial neoplasias, and ejaculatory ducts and verumontanum involved with cancer. Additionally, DAR found 9 PC lesions not previously identified histologically. The positive and negative lymph nodes were correctly identified, and in 3 of 3 benign prostatic hyperplasia patients and 5 of 5 cysts, DAR was negative.

This study demonstrated that 64Cu-TP3805 delineates PC in vivo and ex vivo, provided normal images for benign masses, and is worthy of further studies.

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The primary screening methods for PC are prostate-specific antigen measurement and digital rectal examination (3). However, the reported sensitivity for digital rectal examination is only 55%–68%. For prostate-specific antigen, the specificity is limited because men with benign disease such as prostatic hypertrophy and prostatitis present with elevated levels of the antigen. Its positive predictive value in asymptomatic men has been reported to be only 28%–35%. This predictive value is marginally increased to 49% if prostate-specific antigen estimation is combined with the results of digital rectal examination.

In recent years, PET has emerged as a sensitive modality for imaging oncologic lesions. For PET imaging of PC, such metabolic and biochemical agents as 18F-FDG, 11C-acetate, 18F-acetate, 11C-methionine, 11C-choline, 18F-choline, and 16b-18F-5a-dihydrotestosterone have been investigated.

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The evaluation of peptide receptors in man is needed not only to discover the physiological target tissues of a given peptide but also to identify diseases with a sufficient receptor overexpression for diagnostic or therapeutic interventions. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) receptors have been evaluated in human tumors and in their tissues. The VIP/PACAP receptor subtypes VPAC1, VPAC2, and PAC1 were evaluated in these tissues by determining the rank order of potencies of VIP and PACAP as well as VPAC1- and VPAC2-selective analogues. The VIP/PACAP receptors expressed in the great majority of the most frequently occurring human tumors, including breast (100% receptor incidence), prostate (100%), pancreas (65%), lung (58%), colon (96%), stomach (54%), liver (49%), and urinary bladder (100%) carcinomas as well as lymphomas (58%) and meningiomas (100%), are predominantly of the VPAC1 type. the high VIP/PACAP receptor expression in tumors may represent the molecular basis for clinical applications of VIP/PACAP such as in vivo scintigraphy and radiotherapy of tumors as well as VIP/PACAP analogue treatment for tumor growth inhibition.
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Prostate cancer (CaP) and bladder urothelial cancer (BUC) are the two most common malignancies in urology, and both overexpress VPAC1. VPAC1 is overexpressed at the onset of the malignancy, prior to elevation of PSA, or alteration of cell morphology. We hypothesize that VPAC1 expressed in high density on PC and BUC can be targeted for detection of shed tumor cells (STC) in voided urine, using TP4303, a VPAC1 specific biomolecule labeled with a near infrared fluorophore. The method is simple, noninvasive, rapid and appears to detect STC in patients with known prostate and bladder malignancy with high sensitivity. VPAC1 is a promising and novel approach for accurate and non-invasive detection of CaP and BUC from voided urine.

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Cancer remains one of the most formidable diseases of mankind. Genitourinary cancers, such as those involving prostate (CaP) and bladder urothelium, are common malignancies. However, their noninvasive diagnosis remains challenging. Our investigation pertains to the use of voided urine, in which we selectively identify shed cancerous cells (SCC) by targeting a specific genomic biomarker to distinguish them from normal epithelial cells optically.

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The need is compelling for early and accurate diagnosis of prostate cancer (PC), non-invasively. The goal is to PET image PC using 64Cu-TP3805, specific for VPAC1 receptors, expressed in high density on PC cells, but not on normal cells. 64Cu-TP3805 has (i) high affinity for VPAC1 (Kd = 3.1×10-9M), (ii) excellent stability in-vivo, and (iii) ability to image spontaneously grown PC in transgenic (TRAMP) mice that mimic pathophysiology of human PC.

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