The Threat of Cancer and the NV-VPAC1™ Solution
Despite technological advancements in healthcare, cancer remains a global health threat, accounting for almost 13% of deaths worldwide. Cancer is the second leading cause of death globally [1]. Although cancer screenings have become a controversial topic, the importance of early diagnosis is undisputed [2]. Nevertheless, there is a critical need to further develop diagnostic and imaging techniques that can distinguish which tumors pose a threat, and which do not. The NV-VPAC1™ solution offers compelling pharmacoeconomic cost savings and benefits while eliminating potential health complications from unnecessary biopsies.
The NV-VPAC1™ Oncology Platform technology is composed of 3 products:
1) NV-VPAC1™ In Vitro Diagnostic Test: detects cancer
2) NV-VPAC1™-Cu-64 In Vivo Diagnostic Test: shows specifically where the cancer is located
3) NV-VPAC1™-Cu-67 In Vivo Therapy: targeted cancer cell therapy
The NV-VPAC1™ Peptide Construct
NV-VPAC1™, designed and synthesized by Dr. Mathew Thakur at Thomas Jefferson University (TJU), Philadelphia, PA, is a patented peptide analog technology.
NV-VPAC1™ specifically targets VPAC1 receptors, a subtype of the vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) receptor family [3,4]. The human VPAC1 receptor gene encodes a G protein-coupled receptor that recognizes both VIP- and PACAP-related peptides with high affinity [3,4]. The high densities of VPAC1 receptors occur on the surface of malignant cells and precede histologic changes [5,6].
VPAC1 receptors are overexpressed in numerous cancers to include: [7]
- Brain
- Bladder
- Breast
- Colorectal
- Endocrine
- Endometrial
- Gastric
- Liver
- Lung
- Lymphomas
- Pancreatic
- Prostate
- Thyroid
The NV-VPAC1™ Oncology Platform Technology:
NV-VPAC1™ In Vitro Diagnostic Test:
The NV-VPAC1™ in vitro diagnostic test precisely targets VPAC1 receptors overexpressed on the surface of cancer cells. The shed cell assay, developed by Dr. Mathew Thakur and Dr. Leonard Gomella, Thomas Jefferson University, is a confirmatory test that allows distinction between cancerous lesions and benign masses in order to minimize unnecessary biopsies. Dr. Thakur and Dr. Gomella’s unique shed cell detection is for a variety of epithelial tumors beyond urinary tract malignancies. VPAC1 receptors on shed cells collected from voided urine and other biofluids can be targeted to serve as an early screening for an assortment of cancers.
The NV-VPAC1™ diagnostic urine test is a reliable tool to detect cancer in a noninvasive, inexpensive manner.
NV-VPAC1™-Cu-64 In Vivo Diagnostic PET Imaging Test:
Dr. Thakur hypothesized that radiolabeled biomolecules with a high affinity for VPAC1 receptors could be used in vivo to image cancer cells. Thus, NV-VPAC1™ was modified for radiolabeling with Copper-64 (Cu-64), a positron-emitting isotope, (half-life [t½]=12.7 hours), via a C-terminal diaminodithiol (N2S2) chelator, to enable imaging by positron emission tomography (PET) [8]. This breakthrough technology aids in both the early detection and localization of cancer cells.
Compared to other shorter-lived PET isotopes such as Fluorine-18 (F-18), the longer half-life of Cu-64 provides advantages for delayed imaging. Cu-64 also ships without excessive loss of radioactivity due to physical decay. Dr. Thakur found that Cu-64 is more sensitive than other imaging modalities, identifies all malignant tumors that overexpress VPAC1 receptors, and does not identify benign tumors that do not overexpress VPAC1 receptors.
Current imaging techniques are inadequate, missing up to 30% of cancers [8]. Further, current imaging methods cannot distinguish benign from malignant tumors [9]. Thus, more sensitive imaging methods are needed. Dr. Thakur’s NV-VPAC1™-Cu-64 for PET imaging, which provides VPAC1 receptor-specific tumor imaging, may be advantageous since it can demonstrate the state of malignancy. The NV-VPAC1™-Cu-64 in vivo diagnostic PET imaging test clearly distinguishes between benign and malignant tumors.
Dr. Thakur’s data consistently demonstrates the ability of NV-VPAC1™-Cu-64 for PET imaging to positively detect a variety of cancers. Most importantly, the negative results for benign tissues indicates this technique has high specificity for malignant lesions.
NV-VPAC1™-Cu-67 In Vivo Therapy:
Copper-67 (Cu-67), a beta-emitting radioisotope, is ideally suited for radiotherapy for several reasons. First, Cu-67 can be combined with the same type of radiopharmaceuticals as Cu-64 leading to an efficient theranostic pairing. Secondly, the half-life of Cu-67 ([t½]=2.6 days) is appropriate to deliver a high dose rate to the tumor and allows for optimized repeat dosing [10].
In addition, Cu-67 compares favorably with another standard radioisotope, Iodine-131 (I-131). The longer half-life of I-131 and the higher energy γ ray emission may increase the undesired dose to the patient and medical personnel. Dr. Thakur’s NV-VPAC1™-Cu-67 ensures targeted cancer therapy with reduced radiation exposure in comparison to I-131.
The NV-VPAC1™ Oncology Theranostic Platform Offers Targeted Therapy
NV-VPAC1™-Cu-64 works effectively for prostate and breast cancer diagnosis as a companion diagnostic scan following an annual exam or screening mammogram [11]. The NV-VPAC1™-Cu-64 PET scan targets VPAC1 receptors, overexpressed on the surface of malignant cells, early in the onset of prostate and breast cancers. This confirmatory test allows physicians to quickly determine whether the patient has cancer. In addition, NV-VPAC1™-Cu-67 ensures targeted therapy for treating patients with cancer.
The combined NV-VPAC1™ Oncology platform reduces the number of unnecessary future screenings and biopsies [12]; improves the immediacy of cancer confirmation; minimizes patient anxiety, fear, and depression; and greatly decreases health care costs [13].
About the Author: Jill S. Helmke is the Director of Clinical Trials/Chief Pharmacy Officer at NuView Life Sciences, Inc.
References
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[8] Thakur ML, Aruva MR, Gariepy J, Acton P, Rattan S, Prasad S, et al. PET imaging of oncogene overexpression using 64Cu-vasoactive intestinal peptide (VIP) analog: comparison with 99mTc-VIP analog. J Nucl Med. 2004 Aug;45(8):1381-9.
[9] Welch HG, Passow HJ. Quantifying the benefits and harms of screening mammography. JAMA Intern Med. 2014 Mar;174(3):448-54.
[10] Souliotis GA, Rodrigues MRD, Wang K, Iacob V, Roeder B, Tabacaru G, Yu M, Zanotti-Fregonara P, Bonasera A. A Novel Approach to Medical Radioisotope Production Using Inverse Kinematics; A Successful Production Test of the Theranostic Radionuclide Cu-67. Applied Radiation and Isotopes. 2019 Jan 8.
[11] Hubbard RA, Kerlikowske K, Flowers CI, Yankaskas BC, Zhu W, Miglioretti DL. Cumulative probability of false-positive recall or biopsy recommendation after 10 years of screening mammography: a cohort study. Ann Intern Med. 2011 Oct 18;155(8):481-92.
[12] Braithwaite D, Zhu W, Hubbard RA, O’Meara ES, Miglioretti DL, Geller B, et al. Screening outcomes in older US women undergoing multiple mammograms in community practice: does interval, age, or comorbidity score affect tumor characteristics or false positive rates? J Natl Cancer Inst. 2013 Mar 6;105(5):334-41.
[13] Elter M, Schulz-Wendtland R, Wittenberg T. The prediction of breast cancer biopsy outcomes using two CAD approaches that both emphasize an intelligible decision process. Med Phys. 2007 Nov;34(11):4164-72.