PSMA protein targeting agent and metastatic disease

According to a company press release, Molecular Insight Pharmaceuticals, Inc. presented clinical data earlier today on a development-stage, radiolabeled, small-molecule, molecular imaging pharmaceutical with potential in the diagnosis, staging, and perhaps even the treatment of advanced forms of prostate cancer. These data were presented by Barrett et al. at the 2009 annual meeting of the Society of Nuclear Medicine (SNM) in Toronto. The title of their presentation was, “Targeting metastatic prostate cancer (PCa) in patients using 123I-MIP 1072 and 123I-MIP 1095″ (see abstract 522).

The imaging agent is known as Trofex™. It targets prostate specific membrane antigen (PSMA), a protein highly expressed by prostate tumor cells.

In 2008, Molecular Insight initiated clinical studies of Trofex in patients with documented prostate cancer and confirmed hormone refractory metastatic disease. Two internally developed Trofex compounds, MIP-1072 and MIP-1095, have been evaluated for their capacity to visualize metastatic disease and to define their pharmacokinetic profiles. Both agents rapidly detected metastatic prostate cancer lesions in soft tissues and bone, confirming that targeting the extracellular domain of PSMA is a viable approach for the molecular targeting of this cancer. The compounds were uniquely able to detect metastases within one to two hours after injection.

“Based on the potential demonstrated here, to rapidly and clearly image prostate cancer, we have planned additional studies to investigate the performance of these radiolabeled small molecules in patients with metastatic prostate cancer,” said John W. Babich, PhD, on behalf of Molecular Insight Pharmaceuticals. “Not only does this data demonstrate the capability to rapidly visualize bone metastasis and soft tissue lesions — that may be missed by conventional imaging techniques — imaging can be done in a single day, which is not possible with some of the products currently on the market for imaging recurrent metastatic disease.”

The targeting compound that Molecular Insight Pharmaceuticals developed for imaging is an iodine-123-labeled small-molecule candidate. But when the compound is labeled with iodine-131, the developer believes it may also have the potential to treat metastatic prostate cancer. During 2009, the company plans to complete a proof of concept and dosimetry trial for the detection of prostate cancer. Appropriate results in the additional pilot studies could support a request for fast-track development designation for the detection of metastatic disease.

6 Responses

  1. Correct me if I am wrong, but doesn’t this amount to successful targeting of prostate cancer cells. They are injecting these molecules into a person and they find their way to the cancer cells only. If I have not misunderstood this article, this is huge. Discriminate targeting is the biggest piece of the puzzle. It seems that including a toxic load would not be that much more difficult. I would think this is a major breakthrough. Am I way off base here?

  2. Dear Chris:

    This is far from being the first attempt to deliver targeted therapeutic agents to prostate cancer cells via PSMA. There is a big difference between the theoretical possibility and the effective execution of the idea. To date, despite multiple attempts, I am not aware that anyone has been able to execute this strategy with sufficient effectiveness to get even close to the idea of an approvable drug.

    Now this doesn’t make the idea wrong. It simply means that it may be very difficult to make it work in the real world. If this company has solved the problem, great — but I shall reserve judgment until I see actual evidence of clinical effect in patients with well-defined disease. At least this is one more possibility to keep one’s eye on.

  3. The way the article reads they claim to have successfully targeted PSMA. I don’t, mis-lead again?

  4. Dear Chris:

    You are reading information from a corporate press release. Obviously this is couched in “positive-speak.” But there is no detail.

    What was the percentage of prostate cancer cells that were accurately identified? There is no information. What was the percentage of non-cancerous cells that were inaccurately targeted? There is no information.

    Effective use of targeted therapeutic agents is dependent upon (at least) four things: the sensitivity and specificity of the molecule to bind to the correct target and the effectiveness and safety of the therapeutic capability of the agent to act on the targeted cells. None of this information is provided in the media release issued by this company, but without this information we have no real basis for determining whether this product will be effective on anyone.

  5. That’s true. It’s amazing that their stock has gone crazy over this.

  6. No one ever said that the biotech investor community was particularly intelligent!

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