LUTETIUM-177 PSMA THERAPY

Cancer is caused by the uncontrolled growth and division of cancerous (malignant) cells. Prostate cancer is a tumor that forms in the prostate gland. When prostate cancer cells spread to other body parts and tumors develop, the condition is called metastatic prostate cancer.

Theranostics is a new direction in medicine. This approach allows body imaging using a tumor-specific agent to locate the tumor, its metastases, and its possible future location. It also uses a specific agent with a predetermined therapeutic efficacy for the affected tissues. This approach makes it possible to move from traditional medicine to modern personalized medical procedures. In prostate cancer, Ga-68 PSMA PET/CT allows visualization of tumor tissues of the prostate with high sensitivity and specificity, while specific and targeted therapy of tumor tissues can be carried out using Lutetium 177 PSMA. This is a relatively new and successful method of performing theranostic procedures.

This method consists of the introduction of a radionuclide for internal, super directional irradiation of metastases, which settles inside them due to its affinity for the surface of the tumor (and not due to simple sedimentation in the bone tissue, such as Xofigo and the like). This property of Lutetium-PSMA significantly changes the effectiveness of treatment and its tolerability compared to existing methods in patients with castration resistance (insensitivity to hormone therapy).

How is Lutetium-177 PSMA therapy performed?

PSMA is a type of protein with numerous cellular functions found in the membrane of a healthy prostate cell. While healthy prostate cells express PSMA at very low levels, prostate cancers overexpress PSMA (1,000 times more than healthy prostate cells in general). PSMA may occur in other parts of the body if the prostate cancer has spread to other parts of the body. The Lu-177 atom is a radioactive element that emits radioactive beta particles and can be attached to a PSMA carrier molecule.

With intravenous administration of Lu-177, PSMA moves into tumor tissues, where PSMA is expressed, accumulates in PSMA receptors of tumor tissue, and destroys these cells by irradiation. Because Lu-177 PSMA therapy is directed at cancerous tissues, the radiation dose to other body parts is very small. The portion of Lu-177 PSMA that is not absorbed by tumor cells is excreted through saliva, urine, and feces.

Who is Lutetium-177 PSMA suitable for?

This treatment may be given to patients with metastatic castration-resistant prostate cancer (mCRPC) for whom approved (alternative) treatments are unacceptable.

To be able to receive this treatment, the patient must undergo the following procedures:

• Increased PSMA expression should be demonstrated on Ga-68 PSMA PET-CT images at least two months before treatment.
• Biochemical analysis of blood serum, including serum AST, ALT, creatinine, and PSA, as well as a complete blood count, should be carried out no later than two weeks before the start of treatment.
• Information should be provided on the stage of the disease before treatment, past treatments, procedures, and histological findings.
• The patient should be evaluated by a multidisciplinary team to determine whether Lu-177 PSMA therapy can be initiated.

Lutetium-177 PSMA therapy cannot be performed in the following situations:

• ECOG Capacity Scale (Eastern Joint Cancer Group) = 3 or 4 (unless Lu-177 PSMA therapy is aimed at relieving your symptoms))
• Presence of progressive and uncontrolled disease, including liver and kidney disease and infections

What is radionuclide therapy indicated for?

1. an undoubted indication for Lu-177-PSMA therapy is hormone-resistant prostate cancer (castration resistance) in the presence of progression against the background of drug treatment;
2. a clarifying method for predicting the effectiveness of treatment with Lutetium-177 PSMA is scintigraphy with GA-67 or F-18-PSMA (theranostics).

How is Lu-PSMA radionuclide therapy carried out at RRCRR?

• initial consultation to determine indications for radionuclide therapy is held in room 723 of the radiological building on Wednesdays from 10 am to 12 pm;
• if there are indications for treatment, as well as the possibility of being included in one or another protocol of clinical observation, the patient is hospitalized in the department of radionuclide therapy, and the date of hospitalization is reported at the end of the initial consultation;
• the restrictions when being in a closed mode can be found in detail on the Center’s website and in the patient’s memo;
• on the day of hospitalization, the radiopharmaceutical is administered intravenously using an infusion pump. Further, the patient is monitored using video communication;
• two days later, control dosimetry is performed; if the radiation power from the body is less than the maximum allowable, the patient is discharged from a closed hospital.
• Possible complications: typical complications are nausea, rarely – vomiting, and dry mouth in the next few hours after the administration of the radiopharmaceutical. It is also possible a temporary deterioration in hematopoiesis.

Advantages of Lu-PSMA radionuclide therapy over other methods of treatment of patients with metastases of castration-resistant prostate cancer:

• Anticancer drugs: (doxytaxel, cabazitaxel), Androgen synthesis inhibitors, androgen receptor blockers (abiraterone, enzalutamide). An increase in overall survival during radionuclide therapy with lutetium-PSMA by 1.3 times; adverse events are not severe and occur 6.3 times less frequently. At the same time, since the use of Lu-PSMA in some countries is just beginning, the indications for its use are temporarily narrowed down to cases of disease progression against the background of pharmacotherapy.
• Remote beam radiation therapy: unlike external radiation, in treating radioactive lutetium, there is no limit on the number of irradiated metastases, and multiple applications are possible. Healthy tissues are practically not irradiated (about 1 mm around the tumor), which practically does not lead to classical radiation reactions.
• Radionuclide therapy with radium-223 (Xofigo), Samarium-153, and Strontium-89 is an effective way of long-term treatment of bone pain. However, only the superficial part of the bone metastasis is exposed to the radiopharmaceutical, where there is a protective growth of bone tissue. Unlike the listed “bone” (osteotropic) radiopharmaceuticals, lutetium-PSMA is equally effective in both bone and lung lesions and in metastases to the lymph nodes. The response rate to treatment is up to 60% (almost 5 times more likely) than with radioactive samarium, strontium or radium.