Radiopharmaceuticals
In our laboratory, we use radiopharmaceuticals for PET examinations. These are drugs with national or European registration and marketing authorization. They differ from standard drugs in that they are labeled with a radioactive substance when they are ready for use.
Radiopharmaceuticals are tested, non-toxic and safe for the patient. They are given in minimal amounts (tracers) which do not affect the well-being of the patient. Any use of ionizing radiation in diagnostics or isotope therapy must be justified. In addition, in order to minimize the dose of radiation received by the patient, the activity of radiotracers is selected individually based on body weight, in accordance with the ALARA principle (ALARA – as low as reasonably achievable). This means that we provide the lowest possible activity of the radioactive isotope, with maximum diagnostic benefits. In accordance with Polish and European legislation.
In addition, as part of scientific projects, it is possible to use radiotracers that have not yet been registered and are in the phase of clinical trials.
In our laboratory, we use diagnostic radiotracers labeled with 18F (radioactive fluorine-18 isotope) – produced in a cyclotron at the Radiopharmaceuticals Production Center and 68Ga (gallium-68) – derived from a germanium / gallium generator (68Ge / 68Ga) – synthesized on site in our Radiochemistry Laboratory.
18F-FDG (fluorodeoxyglucose)
Registered and admitted to trading in the territory of Poland.
The most widely used radiopharmaceutical in PET diagnostics. It is used in the diagnosis of oncology, cardiology, neurology and the diagnosis of inflammation and infection.
FDG is a glucose analog that accumulates in cells that use glucose as an energy source. It accumulates in lesions intensively metabolizing glucose. The mechanism of FDG accumulation in the cell is mediated by specific tissue carrier systems that are partially dependent on insulin. Therefore, it is very important to prepare the patient for the examination, as diet, nutritional condition and diabetes affect the cellular uptake of FDG. Fluorodeoxyglucose, like glucose, is transported across the cell membrane into the cell. There it undergoes glycolysis, but only in the first stage of this process. This leads to the formation of fluorodeoxyglucose-6-phosphate (18F), which is “trapped” in the cell and is not further metabolized.
FDG crosses the blood/brain barrier. It is excreted from the body mainly by the kidneys.
18F-FCh (fluorocholine)
Registered and admitted to trading in the territory of Poland.
Radiopharmaceutical product intended for PET diagnostics only. Fluorocholine (18F) chloride is used in cancer patients for imaging cell function, in which the diagnostic point is increased choline uptake by specific tissues. Mainly used in the diagnosis of prostate cancer or in some types of kidney cancer. In addition, 18F-fluorocholine is used to localize ecotopically located parathyroid glands.
Fluorocholine chloride (18F) is an analog of choline (a precursor of phospholipid biosynthesis), in which the hydrogen atom is replaced with 18F. After passing through the lipid bilayer by a system of specific transporters, choline is phosphorylated by choline kinase (CK). In the next step, phosphorylcholine is converted to cytidine diphosphatecholine (CDP-choline) and then incorporated into phosphatidylcholine in the cell membrane. It was found that the activity of CK is increased in cancer cells, which explains the accumulation of choline in these cells and the strong signal of labeled choline after its administration.
18F-FET (Tyrosine)
Radiopharmaceutical product registered in the EU. On special order available under the procedure of direct import. We have the consent of the Ministry of Health to perform a PET/MR examination with 18F-FET in our Unit.
Radiopharmaceutical product exclusively for the diagnosis of malignant tumors of the brain. Used in functional imaging where increased amino acid use is the target.
A product with high sensitivity and diagnostic specificity for gliomas. It is used for non-invasive assessment of the nature of malignant changes in the brain, their staging, helpful in selecting the optimal biopsy site in a brain lesion suggesting glioblastoma. In addition, it shows the viability of glioblastoma tissue before therapy.
Extremely helpful and precise radiotracer in differentiating the potential area of glioblastoma recurrence from a postoperative scar or other changes in the brain, due to the assessment of the viability of the tumor tissue from the brain.
FET is actively absorbed by brain malignant tumor cells. Mainly transported by the amino acid transport system (AAT) L (leucine-preferring) into the cell. The L transport system (preferring leucine) is sodium-independent and carries amino acids with large neutral side chains. The FET is then “trapped” in the tumor cell and does not undergo further protein synthesis.
18F-FBB (florbetaben)
Registered and admitted to trading in the territory of Poland.
The radiopharmaceutical is intended for PET imaging diagnostics in adults only. It is used to image beta-amyloid deposits in the brain of adult patients for the diagnosis of Alzheimer’s disease (AD) or other cognitive disorders. It should be used in conjunction with a holistic assessment of the patient’s clinical picture. A negative scan indicates no or low density of cortical β-amyloid plaques and does not indicate a diagnosis of AD. Florbetaben (18F) works by binding to amyloid plaques in the brain
Limitations of Use – A positive scan alone does not constitute an independent diagnosis of AD or other cognitive impairments as neurotic plaque deposition in the gray matter may be asymptomatic in the elderly and in some neurodegenerative dementias (AD, Lewy body dementia, in Parkinson’s disease). Therefore, it is very important to assess the entire clinical picture of the patient.
68Ga-PSMA
The radiopharmaceutical is made by labeling radioactive gallium (68Ga) chloride in vitro with the PSMA-11 ligand. Labeling set registered in the EU.
A radiopharmaceutical product with high diagnostic sensitivity and specificity, widely used in PET imaging of prostate cancer. Prostate-specific membrane antigen (PSMA) PET has become a promising tool for assessing the severity of the so-called staging as well as the search for biochemical recurrence of prostate cancer.
Currently the most commonly used ligand in PC imaging. Widely used in the following clinical indications:
• Initial assessment of the severity of PC lesions in patients before the planned implementation of therapy
• Suspicion of biochemical recurrence at a very early stage in patients with increasing serum prostate specific antigen (PSA) levels
• Identification of PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) patients for whom PSMA-targeted therapy is indicated
The mechanism of action of 68-gal gozetotide is its binding to cells overexpressing the prostate-specific membrane antigen, PSMA, including PC cells. PET images show the intensity of the 68-gal gosetotide signal in the cell, which in turn indicates the presence of the PSMA protein in the tissues.
Excreted mainly by the kidneys.
68Ga-DOTA-TOC
Labeling set registered in the territory of Poland.
Active substance – edotreotide. After radiolabelling, the resulting 68Ga-edotreotide solution is used for PET imaging of somatostatin receptor overexpression in adult patients with confirmed or suspected well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to locate primary and metastatic tumors .
Diagnostic examination using 68Ga-DOTATOC Positron Emission Tomography (PET) is used to staging and measuring the response to treatment of somatostatin receptor positive tumours.
68Ga-edotreotide is a somatostain analogue. Somatostain is a neurotransmitter in the CNS, but also acts as a hormone that binds to cells of neuroendocrine origin and inhibits the release of growth hormone, insulin and glucagon in the serum. The radiopharmaceutical binds to somatostatin receptors. In vitro, it has high affinity for SSTR2 subtypes and lower affinity for SSTR5.
68Ga-DOTA-TATE
Labeling set registered in the EU. Imported under the procedure of direct import. In our laboratory, we have the consent of the Ministry of Health to perform a PET examination after administering 68Ga-DOTA-TATE.
68Ga-DOTA-TATE is intended solely for PET diagnostics to locate neuroendocrine tumors (NET) with the presence of somatostatin receptors in adult and pediatric patients.
DOTA-TATE, also known as DOTA-O-Tyr3-Octreotan, is a cyclic 8-amino acid peptide with a covalently bonded chelator (DOTA). The peptide has the following amino acid sequence: H-D-Phe-Cys-Tyr-D-Trp-Lys-Thr Cys-Thr-OH, contains one disulfide bond. The mechanism of action of 68Ga-DOTA-TATE consists in binding to somatostatin receptors, with the highest affinity to subtype 2 receptors (sstr2). It binds to cells that express somatostatin receptors, including cancer cells that overexpress these receptors. Galium-68 (68Ga) is a β+ emitting radionuclide whose emission efficiency allows positron emission tomography (PET) imaging. 68Ga-DOTA-TATE is distributed to all organs expressing sstr2 receptors, such as pituitary, thyroid, spleen, adrenal, kidney, pancreas, prostate, liver and salivary glands. There is no uptake in the cerebral cortex or the heart, and uptake in the thymus and lungs is usually low. The product is mainly excreted by the kidneys.
68Ga-FAPI
The product is not registered in Poland or the EU. In the phase of clinical trials. Available only as part of scientific projects with the consent of the bioethics committee.
After labeling with the radioactive 68Ga isotope, the product is used for PET imaging diagnostics. Used in the diagnosis of oncology, as well as disease entities with fibrosis. Thanks to the PET diagnostic method with 68Ga-FAPI, it is possible to visualize e.g. wound healing, fibrosis (liver, kidney, lung) and inflammation (e.g., rheumatoid arthritis, Crohn’s disease, atherosclerosis, myocardial ischemia). The latest literature reports indicate that it is widely used in the diagnosis of a number of types of cancer, both primary and metastatic tumors. FAP overexpression is found in fibroblasts associated with various cancers. 68Ga-FAPI shows fast accumulation of the tracer in target lesions and a low background signal, resulting in excellent imaging properties. According to the latest literature reports, the fibroblast activation protein (FAP) inhibitor (FAPI) labeled with gallium-68 (68Ga) is a radiopharmaceutical that can help detect small primary or metastatic lesions in key organs such as the brain, liver, pancreas and gastrointestinal tract.
The highest accumulation of 68Ga-FAPI was noted in sarcoma, esophageal cancer, breast cancer, cholangiocarcinoma and lung cancer. The lowest radiotracer uptake was observed in phaeochromocytoma, renal cell carcinoma, differentiated thyroid carcinoma, adenoid cystic carcinoma and gastric cancer. Moderate uptake was found in hepatocellular, colorectal, head and neck, ovarian, pancreatic, and prostate cancers.
Physiologically, fibroblasts are ubiquitous throughout the body. They express dipeptidyl peptidase 4 with no or very low expression of FAP. Tumor stromal cells, or cancer-associated fibroblasts, differ from normal fibroblasts in that they provide FAP as a target with relatively high tumor-specific expression, and FAP inhibitors (FAPIs) have already been developed as anticancer drugs. The presence of the DOTA chelator in the molecular structure enables coupling of FAPI molecules with therapeutic emitters such as lutetium-177 and yttrium-90 for theranostic applications. Cancer-associated fibroblasts (CAF) often indicate a poor prognosis for patients. CAFs often express elevated levels of the type II fibroblast-activated transmembrane serine protease (FAP), which plays a key role in the migratory, invasive, and angiogenic activity of tumors. Recently, a new generation of PET radiotracers based on specific quinoline FAP inhibitors have been developed, which can be used for precise targeted imaging of tumor tissue. 68Ga-FAPI PET shows a high degree of tracer uptake within the tumor, low uptake in normal tissues and fast clearance, which results in very good tumor visibility and an appropriate ratio of imaged cells to the background.
