PSMA- and DOTA-TATE positron emission tomography (PET) imaging is currently the most accurate and specific method for detection and imaging of cancer cells present in the body.
The surface of cancer cells often contains certain enzymes, receptors or proteins highly specific to each type of cancer, generically surface markers. Targeted radioligand procedures use these highly specific surface markers on the tumor cells as a target structure both for diagnosis and for treatment. Hence the blend name of this medical field - theranostics, i.e. the combination of therapy and diagnostics of the target.
How does the diagnostics work?
The so-called ligands, i.e. substances that dock to the surface markers, are loaded with nuclides or radioactive substances, what turns them into labelled ligands in medical parlance. For diagnostics purposes, the ligand is loaded with the radioactive substance gallium 68Ga.
The 68Ga-labelled biomarkers are then injected intravenously and thus search for their respective target on the tumor cell via the bloodstream. Thereafter a PET/CT scan is performed, which allows to detect the locations where the substance has accumulated and thus clearly and accurately indicates the location of tumors and metastases. This PET/CT-scan is also necessary to assess whether radioligand therapy is applicable, as its success depends on the presence (or expression in medical jargon) of the surface markers.
The surface marker specific to the prostate cancer is an enzyme called prostate-specific membrane antigen or PSMA. In almost all cases this enzyme is very abundant on the surface of both the primary tumor and its metastases. These are then described as PSMA-positive or PSMA+. Next to PSA, PSMA is a crucial biomarker for assessing the progression of cancer, once it has spread beyond the primary tumor to other parts of the body. The molecular PSMA imaging is in fact significantly more precise than a simple PSA value in blood, because it tells you where exactly in the body cancer has spread. Therefore, PSMA imaging can inform the decisions on further treatment.
Very rarely (in < 10% of cases) PSMA is expressed in quantities insufficient for treatment. This can be the case either with very low PSA levels (e.g. under antihormonal therapy) or at very advanced stages. Ultimately, only 68Ga PSMA-PET/CT can give an unambiguous answer.
With regard to PSMA-therapy imaging is of crucial importance as it shows which lesions are being treated, thus offering the possibility of a direct measurement and assessment of the therapeutic success.
The surface marker specific to the neuroendocrine tumors (NET) is called somatostatin receptor. A somatostatin-like substance called DOTATATE is used as a ligand. Hence the name of the treatment and imaging. As with the PSMA, Dotatate is loaded with the radioactive nuclide 68Ga and injected intravenously, and the patient PET-scanned. Thereby all lesions in the body with the increased density of somatostatin receptors (NETs and the smallest metastases) can be detected and represented.
Especially in the case of prostate cancer, it has already been shown that even small lesions measuring only a few millimeters can be detected even at low PSA levels after therapy of the primary tumor. Our team was also able to show that this has a decisive influence on the further treatment decision and is thus often groundbreaking for the patient and the attending physician. Even before prostate cancer therapy, PSMA-PET often provided valuable, therapy-changing information.