PSMA- and DOTA-TATE positron emission tomography (PET/CT) imaging is currently the most accurate and specific method for detection and imaging of prostate and neuroendocrine cancer cells respectively present in the body. FAPI PET/CT is a pan-cancer diagnostics method targeting the tumor microenvironment (TMI) of many wide-spread types of solid tumors, like breast, colon and pancreatic carcinomas.
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.
If you have been diagnosed with the primary prostate cancer with no lymph node involvement or metastasis detected, you can check here if PSMA PET/CT is recommended for you.
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/CT often provided valuable, therapy-changing information.
This PSMA nomogram in the form of an easy online calculator helps determine, which group of patients are most likely to benefit from the addition of a PSMA PET/CT.
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.
68Ga-FAPI is a pan-cancer theranostic diagnostics directed at fibroblast activation protein (FAP) found in the cancer-associated fibroblasts (CAF). It is the latest molecular diagnostic method developed and compares favourably with a present mainstay of oncological staging 18F-FDG PET/CT for various reasons: it simplifies the clinical workflow, and it is more precise.
Tumor masses consist of cancer cells but also vascular structures, inflammatory cells, collagen and fibroblasts (the most common type of cell in connective tissue) that together make up the tumor stroma or tumor microenvironment (TMI). Several highly prevalent cancers, such as breast, colon and pancreatic carcinomas, are characterized by a strong growth of such fibrous tissue. The stroma can account for up to 90% of the mass in such cancers. Moreover, metastasizing process is very complex and involves the forming of the stroma first - before the actual cancer cells. It has been detected that these cancer-associated fibroblasts (CAFs) contain or express a so-called fibroblast activation protein (FAP), whereas its expression in normal tissues is absent or low.
So FAP presents an ideal pan-cancer target structure for targeted delivery of radiopharmaceuticals. With the tumor stroma making 90% of the tumor volume, stroma-targeted FAPI PET imaging is more sensitive in detecting small cancer lesions at the very early stages.
Besides sustaining and nurturing cancer cells, tumor microenvironment seems to possess immunosuppressive characteristics that protect cancer cells from the body’s own immune response and the conventional therapies. Here you can read more about the development of the targeted molecular nuclear therapy directed at FAP.