Antibodies and Small Molecules: Two Distinct Tools to Target PSMA

Prostate-specific membrane antigen (PSMA) is a molecular marker present in the surface of virtually all prostate cancer cells. It may be targeted by various molecular agents which bind to PSMA. This enables a concentrated strategy to find and picture or cure prostate cancer cells where they are in the body, such as the cells that have escaped (metastasized) to other organs.

The most frequently used agents to target PSMA fall in to two groups: small molecules (also known as peptides, ligands, or inhibitors) or electrons (also termed monoclonal antibodies).

Little molecule- and antibody-based molecules that bind to PSMA have distinct physical characteristics and these have implications on how the molecules circulate throughout the body.

For example, peptides and other tiny molecules that aim PSMA are much smaller compared to antibodies -- approximately 100-fold smaller. As a result of the small dimensions, peptides can rapidly travel through blood vessels and disperse throughout all body cells -- both normal and tumor -- and they're also quickly excreted by the liver into the urine and bladder.

Conversely, the bigger antibodies tend to stay inside the circulating blood and circulation more selectively through the larger, abnormal blood vessels within tumors than the vessels from normal tissues. Their large size prevents them from being excreted by the kidneys. Due to these properties, peptides can penetrate tumors, in addition to normal tissues, rapidly and then vanish from your system immediately, in minutes ; antibodies take more time to travel and input the tumor, however this is compensated for by the longer amount of time they invest in the body (days to weeks) and their diminished likelihood to permeate into normal tissues. Visit our website to get more info about antigens for antigens for Helicobacter pylori testing.

From a diagnostic imaging perspective, small molecules are typically better, as the rapid excretion of the radiolabeled peptide quickly reduces the radioactive background "noise" found on a scan. Additionally, using small molecules means that patients can also be injected with imaging agents and then undergo scans immediately thereafter (on precisely the same day within 1-3 hours). Physicians can see decent comparison of the cancerous cells compared to other parts of the body with this particular method. In comparison, patients need to return approximately 3-8 days following infusion with a monoclonal antibody for scans. A number of the advantage of using small molecules would be offset from the fact that they are excreted via the urine and accumulate in the urinary tract. This may lead to an intense signal in the urinary tract region of the scanning, adjacent to the prostate gland and lymph nodes in the pelvis, thus possibly obscuring these potential sites of tumor. On the other hand, some Compounds are consumed by the liver, obscuring visualization of the organ. Antibody fragments such as so-called "mini-bodies" (derived in the entire antibody), are half the size of a normal antibody but still big enough in order to not be excreted in the urine, and therefore, they may provide enhanced imaging of the prostate as well as the pelvic area. This is currently under investigation at Weill Cornell Medicine and New York-Presbyterian Hospital.

The nuances of these molecular targeting agents aside, it is clear that both peptide-, antibody or mini-body-based agents provide significantly improved targeted molecular imaging of prostate cancer in comparison to traditional modalities like bone, CT, and MR scans and have some advantages over glucose (FDG), sodium fluoride (bone), choline, or fluciclovine (FACBC) PET scans.

Treatment

From a therapeutic perspective, there are theoretical benefits of the quicker tumor penetration of this smaller molecule targeting agents, but this might be offset by their quick disappearance and their ability to impact normal tissue. The longer time antibodies spend circulating in the body provides for a greater sum of the treatment agent to get internalized to the cancer cells, allowing higher uptake of the payload agent (such as a radionuclide) that is being delivered to kill the cancer cells. Furthermore, some antibodies might also be engineered to create an immune response.

Can uptake in various body regions lead to unwanted effects?

The different characteristics of small molecules and antibodies confer advantages and pitfalls when targeting PSMA on cancer cells in the body. Because of their small size, small molecules/peptides can penetrate through the depths of their tumor speedily, but they also easily target ordinary tissues that express reduced levels of PSMA such as the salivary glands, small intestine, and kidneys. When using as a curative delivery vehicle, this might lead to dry mouth, nausea, or delayed kidney damage. Fortunately, no substantial kidney damage was seen in people to date, but the number of individuals treated on prospective clinical trials stays modest and follow up is short. An antibody, on the other hand, does not target salivary glands or erections since its bigger size leads to comparatively limited accessibility to those normal websites. However, it circulates in the body for a longer period of time involving high circulation through the bone marrow. Antibodies tagged with radioactive particles may therefore contribute to non-specific unwanted effects such as temporary decreased blood counts. This is a common (expected) toxicity about the dose and schedule of the radiolabeled antibody.

Presently, it is not understood if peptide-based or antibody-based targeted PSMA prostate cancer treatments provide better results, but the two approaches offer therapeutic benefit to patients. At Weill Cornell Medicine and New York-Presbyterian Hospital -- where we have two decades of experience pioneering prostate cancer and treatment with PSMA-targeted representatives -- we are the only center in the world currently able to offer both kinds of imaging and treatment modalities and plan to combine both within different patients. We hypothesize that are going to have the ability to use the positive properties of every targeting representative at marginally lower than highest doses to provide a greater amount of therapeutic payload into tumor with significantly less to normal organs, further enhancing the tumor kill : side effect ratio and also have initiated a clinical trial testing this approach.

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