How long do prostate cancer cells continue to die after a Lutetium-177 (LU-177) infusion?

Duration of Prostate Cancer Cell Death After Lutetium-177 Infusion

Prostate cancer cells continue to die for up to 6.647 days (the physical half-life of Lutetium-177) after infusion, with the radiation effect persisting for approximately 45 days until 99% of the radioactivity is eliminated. 1

Physical Properties of Lutetium-177 and Its Mechanism of Action

• Lutetium-177 (Lu-177) decays to stable hafnium-177 with a half-life of 6.647 days, emitting beta-minus radiation with a maximum energy of 0.498 MeV (79%) and photonic radiation (γ) of 0.208 MeV (11%) and 0.113 MeV (6.2%) 1
• The beta-minus emission from lutetium-177 induces cellular damage by formation of free radicals in target cells and neighboring cells, causing ongoing cell death during the radioactive decay process 1
• The physical decay chart of Lutetium-177 shows that after 7 days, approximately 48.2% of the initial radioactivity remains; after 14 days, 23.2% remains; and after 30 days, only 4.4% remains 1

Pharmacokinetics and Elimination

• The mean terminal half-life of lutetium Lu-177 dotatate in the body is 71 (±28) hours 1
• Lutetium Lu-177 is primarily eliminated through the kidneys with cumulative excretion of 44% within 5 hours, 58% within 24 hours, and 65% within 48 hours following administration 1
• Based on the physical half-life of lutetium-177 and the terminal half-life of lutetium Lu-177 dotatate, greater than 99% of the administered radioactivity will be eliminated within 14 days after administration 1

Treatment Protocol and Dosing Schedule

• Standard Lu-177-PSMA therapy typically consists of 3-5 cycles administered at 6-12 week intervals, with each cycle delivering 5.55-7.4 GBq (150-200 mCi) of radioactivity to PSMA-expressing tumor cells 2
• The European Association of Nuclear Medicine recommends 4-6 cycles of Lu-177-PSMA treatment at 6-week intervals for metastatic castration-resistant prostate cancer (mCRPC) 2
• The time interval between treatment cycles (6-12 weeks) suggests that the therapeutic effect of each dose continues for several weeks after administration 3

Clinical Evidence of Ongoing Response

• In clinical practice, response assessment is typically performed 8-12 weeks after treatment initiation, indicating that the therapeutic effect continues well beyond the physical half-life of the isotope 4
• Studies have shown that continuing Lu-177 therapy beyond two cycles is reasonable and recommended for patients who have not progressed, even if lesions have not yet shown significant reduction, suggesting ongoing therapeutic effect between cycles 2
• The VISION trial demonstrated that Lu-177-PSMA-617 significantly prolonged imaging-based progression-free survival (median 8.7 vs 3.4 months) and overall survival (median 15.3 vs 11.3 months) compared to standard care, indicating durable response to treatment 5

Radiation Safety Considerations

• During the first 2 days after treatment, high levels of radioactivity excretion in urine require special precautions 3
• Patients should observe rigorous hygiene to avoid contaminating persons using the same toilet facilities for 1 week following treatment 3
• Women of childbearing potential should use effective contraception while undergoing treatment and avoid pregnancy for at least 6 months thereafter, indicating potential long-term effects of the radiation 3

Practical Implications

• The continued cell-killing effect of Lu-177 means that clinical response may not be immediately apparent and should be assessed after sufficient time has passed for the full therapeutic effect to manifest 2
• Regular monitoring of hematologic parameters is essential as myelosuppression can be cumulative with additional cycles, suggesting ongoing biological effects between treatment cycles 2
• Extended therapy with Lu-177-PSMA beyond 6 cycles has been shown to be safe without increased grade 3-4 toxicity, suggesting that the radiation effect can be safely repeated in responding patients 4