Frequently Asked Questions

Why was Oncardia developed?

In the late 1990s, M.D. Anderson was interested in developing an alternative molecular imaging technology that could overcome the drawbacks specific to FDG-PET and that could be utilized on SPECT cameras.  This led to the creation of EC-Technology which was licensed to CellPoint. During the ensuing years the first product compound Oncardia went through several synthesis and reformulation processes necessary to transform the science into a commercially viable product compound. Oncardia’s drug conjugate technology functions as a highly stable chemical bridge capable of linking tissue specific ligands (sugar analogues, proteins, peptides, steroids, etc.) or pharmaceutical compounds to radioisotopes (hot or cold) for diagnostic and therapeutic purposes.

Why the need to develop a one-vial Oncardia kit?

The majority of radiopharmaceutical imaging agents are either produced in a cyclotron for PET applications which creates logistical issues or they use multi-vial kits mostly in SPECT applications which can complicate and elongate the unit dose preparation process by the radiopharmacist. A one-vial kit for Oncardia unit dose preparation adds convenience and greater certainty to QA/QC which should help facilitate adoption.

Why was glucosamine used as opposed to deoxyglucose which is used in FDG for PET imaging?

Although FDG, like Oncardia makes full use of the glycosylation process to accumulate in the hyperactive tumor cell, FDG gets trapped in the cell cytoplasm and cannot be metabolized further. Conversely, Oncardia which uses glucosamine is completely metabolized and is transported via the hexosamine biosynthetic pathway into the cell nucleus. The mechanism of actions of FDG compared to Oncardia are similar in certain respects and very different in other respects. The differences are what make Oncardia a potentially superior target specific compound compared to FDG in terms of false positives and false negatives. In addition, Oncardia can serve as the target specific backbone for therapeutics wherein FDG cannot due in part to its uptake in the normal brain, heart, muscles following exertion, and infected and inflamed tissue.

What is the difference in the Mechanism of Action of Oncardia compared to FDG?

Malignant cells express increased levels of Glut 1 and Glut 3 transporters as well as increased hexokinase activity when compared to normal cells. Both Oncardia and FDG enter the diseased cell by utilizing the Glut 1 and 3 transporters. Once 18F-FDG enters the cell, it is phosphorylated by hexokinase II to become 18F-FDG-Phosphate. Because 18F-FDG is missing the 2-hydroxyl group needed for further glycolysis, it is trapped in the cell cytoplasm, a process known as “metabolic trapping”. When Oncardia enters the diseased cell, it is picked up by the Hexosamine Biosynthetic Pathway and O-linked glucosamine transferase (OGT), which are over expressed when the cell is in a diseased state.  OGT is a key enzyme Isilent oncogene for glycosylation during the cancer revolution.  As a glycoprotein, Oncardia then translocates through the cell membrane into the cell nucleus – creating an ideal platform for targeted diagnostics and therapeutics. Oncardia’s translocation into the nucleus drives uptake independent of glucose, yielding improved diagnostic accuracy in the presence of inflammation/infection.

What are ischemic memory capabilities of Oncardia?

Ischemic memory is a term being used to describe the ability of 99mTc-Oncardia to detect the presence and extent of impact to the myocardium for an extended time period following the MI. In canine studies, investigators found that ischemia was detected eight weeks post MI where the heart was remodeling. Once glucose depletion activates the Hexosamine Biosynthetic Pathway, the ischemia is and remains detectable until the glucose depletion returns to normal. Thus, Oncardia can detect ischemia from the moment a cardiac event occurs until the heart returns to normal function.

What impact do you see in cardiac applications for Oncardia after FDA approval?

CARDIAC APPLICATIONS (Estimated Procedures Per Year)

  1. Detection of an AMI in the ER (1.5 MM: novel application)
  2. Detection of a remote acute MI: silent acute MI occurring several days to weeks in the past (800 K: novel application)
  3. Alternative to traditional MPI (5 MM: a clinically viable alternative to SPECT: MPI imaging)
  4. Objectively determining the efficacy of therapy: intervention or medical (1 MM: replacement technology)
  5. Diagnosing, staging and monitoring efficacy of therapy for CHF (3.5 MM: novel application)
The company believes that patients with as little as a 30% flow restriction can be successfully imaged with Oncardia. Please explain?

The presence of CAD does not equate to myocardial disease (ischemia). Rather, Oncardia is metabolized in the nucleus of the cell and is target specific for ischemia if the CAD is sufficient to cause ischemia. For an MPI procedure, the degree of stenosis needs to be >70 %. However, it is possible that ischemia will be present in patients with a lower degree of stenosis if they have a chronic myocardial disease such as CHF. Such patients could be successfully imaged for ischemia for any degree of flow restriction. The clinical challenge is to determine how to identify patients who will have early onset CAD, but not be symptomatic. A CTA scan or a specific blood and urine analysis may be the best way to identify a patient for further investigation which would include an Oncardia-SPECT scan to determine if the patient has suffered any cardiac damage due to ischemia. The objective is to address CAD as early as possible for the intervention of medical management.

Which cardiology patient groups do Cell Theranostics feel will benefit the most with Oncardia?

For cardiac applications, the following patient groups will benefit the most:

  • Patient Convenience. Any patient, especially the elderly, will benefit from the elimination of a stress procedure in most cases. In the U.S., nuclear cardiologists use exercise coupled with pharmacologic injection in approximately 75% of MPI procedures.
  • Diagnostic Accuracy. Oncardia should benefit all patient groups in terms of significantly greater diagnostic accuracy vs. traditional MPI – SPECT
  • The ER. Oncardia should provide the ER with a highly useful nuclear cardiac tool to verify the diagnosis of an AMI within the ER physician’s triage timeframe
  • Remote AMI. Oncardia should benefit patients who have suffered a remote AMI (silent AMI occurring days to weeks prior to the visit to the cardiologist or even the ER)
  • Efficacy of Therapy. Patients and their physicians who need an objective assessment of efficacy of therapy (intervention or medical)
  • Oncardia could potentially be used to diagnose and stage CHF and monitor to assess the efficacy of treatment for the patient’s CHF
What is the first therapeutic application that Cell Theranostics plans to commercialize using the Oncardia chelator technology?

Combination Platinum-Oncardia and 187Re-Oncardia for the treatment of lung cancer, followed by aggressive diffuse type B-cell lymphoma, and head and neck cancer. Next, 177Lu-Oncardia.   Cell Theranostics has been conducting pre-clinical research on Platinum-Oncardia and 187Re-Oncardia at the University of Texas M.D. Anderson Cancer Center. Platinum-Oncardia is being positioned as the initial high yield therapeutic dose followed by 187Re-Oncardia given orally as maintenance therapy. These advantages include a much lower dose of platinum (10-15 mg) compared to 400 mg of Cisplatin and significant lower side effects.

The refence standard for Platinum-Oncardia is Cisplatin or oxaliplatin that does not have an active transport system.  Platinum-Oncardia should be the first-in-class water soluble platinum drug to target OGT in hexosamine pathway-directed therapy. The MOA of delivering Platinum-Oncardia is the same as 99mTc-Oncardia.  The patient would first be imaged with 99mTc-Oncarida which will provide the dosimetry of the primary and secondary lesion.  The dose of Platinum-Oncardia would be calculated by the dosimetry number and the patient’s weight.  Using this targeted system should enable 90% plus of the platinum to go to the cancer cells not healthy cells.  The patient would be imaged after 4 weeks. Using the dosimetry calculation, the oncologist can accurately determine the patients’ response to Platinum-Oncardia therapy and if that patient should receive another dose of Platinum-Oncardia or move to a different therapeutic.

Please explain the Beta Cell theranostic program?

Cell Theranostics is using the same Oncardia theranostic model with our beta cell conjugate technology. Using of beta-cell mapping DTPA, 99mTc-DTPA-Nateglinide is being used to image and monitor the insulin-receptor function in pancreatic beta cells for the early diagnosis of pancreatic diseases, diabetes, cancers and evaluation of therapeutic responses.177Lu- DTPA-Nateglinide is being used to conjugate water soluble 177Lu- to insulin receptors to pancreatic and neuroendocrine carcinoma with minimum damage to healthy cells. Cell Theranostics is also working with the University of Chicago Medical Center to study 99mTc-DTPA-Glipizide to evaluate its ability to distinguish Type I and Type II diabetes.

Please explain your N4 Technology program?

N4 Technology is being used to develop new SPECT as well as a new class of PET imaging agents that will be labeled with generator-based radioisotopes (as opposed to cyclotron-based radioisotopes such as 18F that is currently the radioisotope used with FDG). The company believes that generator-based radioisotopes will be more cost effective and provide greater flexibility in the development of new agents. The first product under development is a SPECT imaging agent, 99mTc-N4-Tyrosine. This product will be used to assess tyrosine kinase activity to help determine which patients with lung or breast cancer, for example, will benefit from anti-EGFR-tyrosine kinase therapy. In addition, N4 Technology compounds are being evaluated for imaging and treating neuroendocrine tumors and for diagnosing, assessing and potentially treating patients with Parkinson’s, Huntington’s and Alzheimer’s as well as certain other diseases affecting the central nervous system.