The abbreviation PRLT stands for "PSMA Radio-Ligand Therapy" (synonym: radio-ligand therapy) and is a treatment method for patients with advanced prostate cancer, where the standard hormone treatment or chemotherapy is no longer effective.

Targeted irradiation of the tumor cell "from within", sparing the healthy tissue

Prostate cancer and its metastases express relatively higher quantities of the prostate-specific membrane antigen (PSMA) on their surface. PSMA serves as a target structure for the PSMA small molecule (ligand) attached to the radioisotope Lutetium-177 (Lu-177). The radio-ligand binds to the tumor cell, which is selectively irradiated from within the cell and thereby destroyed. As range of the radiation emitted is only up to a few millimeters, healthy tissue is largely spared. Cure is rare with radio-ligand therapy, but it is able to alleviate symptoms and delay progression of the tumor disease.

PRLT is usually performed using the beta emitter Lu-177. The alpha emitter Actinium-225 (Ac-225) has a much higher energy compared to Lu-177 with a very short range, which results in a higher rate of double-strand-DNA-breaks in tumor cells. Ac-225 PSMA is a novel therapy option, which can be effectively used after failure of PRLT using Lu-177, or in patients with extensive disease, including bone marrow involvement.

The indication for PRLT is confirmed in the interdisciplinary tumor board, comprising medical specialists from different disciplines (urology, oncology, internal medicine, nuclear medicine, and radiology). The current tumor status, previous treatments (surgery, hormone therapy, chemotherapy, radiation, etc.) and imaging (PET/CT, CT, MRI, etc.) are taken into account. Decisions on therapy planning are taken by consensus, and appropriate recommendations are made accordingly. A pre-therapy Gallium-68 PSMA PET/CT is necessary in order to determine the PSMA expression of metastases, and thus, to assess the feasibility for PRLT. In addition, function of the kidneys and salivary glands must be examined in advance by means of a renal and salivary gland scintigraphy, respectively. Relevant laboratory values (e.g. complete blood count, parameters of renal as well as liver function, electrolytes and PSA) are also required to assess the suitability for PRLT.

Due to radiation protection regulations in Germany, PRLT requires an inpatient stay of at least 48 hours following the radiopharmaceutical injection on our therapy ward. In general, but catering to the individual patient, three to four therapy cycles are performed at intervals of approximately 8 weeks.

Lu-177 PSMA is administered over about five minutes using a dedicated radionuclide therapy infusion system via an intravenous access, under medical supervision. This is followed by an infusion of electrolyte solution, often with addition of a diuretic, to accelerate the excretion of the radioactive substance through the kidneys, thereby maintaining radiation exposure to the healthy tissue as low as possible.

In order to assess the uptake and bio-distribution of the injected radiopharmaceutical in the patient's body, a whole-body scintigraphy along with a three-dimensional SPECT/CT is performed on the days following PRLT. With the help of these images, it is possible to estimate the absorbed dose delivered to the tumor and healthy tissue of the individual patient. This information is important for further therapy planning, and to predict response to therapy and possible side effects.

In general, PRLT is a well-tolerated therapy. However, side effects can occur as with any other therapy or medication.

The most common, usually mild and reversible (short-term), adverse effects observed after and/or under radio-ligand therapy are:

• Short-term increase in pain (so-called "flare phenomenon")
• Nausea
• Constipation
• Fatigue

However, these symptoms can be treated with medications.

Other possible side effects on a longer term are:

• Bone marrow suppression (usually temporary)
• Impairment of the salivary gland function causing dry mouth (usually mild and reversible)
• Kidney dysfunction (rare and usually mild to moderate)

Following PRLT, regular clinical and imaging follow up (restaging) is essential. The frequency and duration of restaging is personalized for each patient and planned following interdisciplinary consensus, including the primary care physician and the oncologist of the patient.

The restaging at our Clinic for Nuclear Medicine includes a concise clinical review including questions regarding current symptoms of the disease (for e.g. pain, dryness of mouth etc.), as well as the assessment of laboratory values (blood count, liver and kidney function tests, PSA, etc.), the monitoring of renal and salivary function by means of scintigraphy, and other imaging procedures. As a rule, this follow-up examination takes place on an outpatient basis.

With regard to imaging, PET/CT as well as CT and MRI are performed according to the guidelines. If several examinations are necessary, but cannot be completed in one day, it is possible to stay overnight in the hospital provided guest rooms.

Finally, the interdisciplinary tumor board discusses the further course of clinical management following review of the restaging findings and makes the appropriate recommendations for the patient.