Pluvicto®▼ (lutetium [177Lu] vipivotide tetraxetan) is indicated for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy or who are not medically suitable for taxanes.1

Locametz®▼ (gozetotide) is for diagnostic use only. Locametz, after radiolabelling with gallium-68, is a radioactive diagnostic agent indicated for the identification of prostate-specific membrane antigen (PSMA)-positive lesions by positron emission tomography (PET) in adult patients with prostate cancer.2

 

Mechanism of Action (MoA)

Pluvicto is a PSMA-targeted radioligand therapy (RLT) that delivers DNA-damaging radiation to PSMA-positive bone, nodal, and visceral metastases.1,3–7

Pluvicto targets PSMA-positive cells, including prostate cancer cells1

The MOA of Pluvicto can be broken down into a few key steps:

Graphic to represent the composition of Pluvicto.

Pluvicto comprises 2 key components:
lutetium-177, a cytotoxic radionuclide, and PSMA-617, a PSMA-targeting ligand.1

 

Image to highlight how Pluvicto binds to PSMA on prostate cancer cells.

As determined by pre-clinical research, Pluvicto binds with high affinity to PSMA, a transmembrane protein overexpressed on prostate cancer cells.1
After binding to PSMA, PLUVICTO undergoes endocytosis and is internalised into the cell.1,8–10

 

Image to highlight how Lutetium-177 emits DNA-damaging radiation within the cell causing single- and double-stranded DNA breaks in targeted cells as well as surrounding cells.

As determined by pre-clinical research, Lutetium-177, (the cytotoxic radionuclide of Pluvicto), emits DNA-damaging radiation within the cell.1,10
The short path length of the radiation emitted by Pluvicto, (approx. 2 mm max.), causes single- and double-stranded DNA breaks in targeted cells as well as surrounding cells, which can lead to cell death.1,9–11

 

  • PSMA scanning enables you to see and target PSMA-positive mCRPC2,5,13,14
  • The high sensitivity of PSMA scanning detects PSMA-positive bone, nodal or visceral metastases13–16
  • PSMA imaging establishes patient eligibility for PSMA-targeted RLT6

The most common adverse reactions (≥20%) occurring at a higher incidence in patients who received Pluvicto + BSoC were fatigue (43.1%), dry mouth (39.3%), nausea (35.3%), anaemia (31.8%), decreased appetite (21.2%) and constipation (20.2%).1 Clinically relevant adverse reactions in <5% of patients included dry eye, vertigo and pancytopenia (including bicytopenia).1

Please refer to the Pluvicto Summary of Product Characteristics for the full list of Adverse Reactions.

 

ADR, adverse drug reaction; AR, androgen receptor; BSoC, best standard of care; DNA, deoxyribonucleic acid; mCRPC, metastatic castration-resistant prostate cancer; MOA, mode of action; PET, positron emission tomography; PSMA, prostate-specific membrane antigen; RLT, radioligand therapy.

References:

  1. Pluvicto®▼ (lutetium [177Lu] vipivotide tetraxetan) Summary of Product Characteristics. 
  2. Locametz®▼ (gozetotide) Summary of Product Characteristics.
  3. Benešová M, et al. J Nucl Med 2015;56(6):914–920.
  4. Fendler WP, et al. J Nucl Med 2017;58(11):1786–1792.
  5. Hofman MS, et al. Lancet Oncol 2018;19(6):825–833.
  6. Sartor O, et al. N Engl J Med 2021;385(12):1091–1103.
  7. Violet J, et al. J Nucl Med 2019;60(4):517–523.
  8. Liu H, et al. Cancer Res 1998;58(18):4055–4060.
  9. Rajasekaran SA, et al. Mol Biol Cell 2003;14(12):4835–4845.
  10. Ruigrok EAM, et al. Eur J Nucl Med Mol Imaging 2021;48(5):1339–1350.
  11. Sartor O, et al. N Eng J Med 2021;385(12):1091–1103. Supplementary appendix.
  12. Kassis AI, et al. Semin Nucl Med 2008;38(5):358–366.
  13. Maffey-Steffan J, et al. Eur J Nucl Med Mol Imaging 2020;47(3):695–712.
  14. Vlachostergios PJ, et al. Front Oncol 2021;11:630589.
  15. Woythal N, et al. J Nucl Med 2018;59(2):238–243.
  16. Schmuck S, et al. J Nucl Med 2017;58(12):1962–1968.

 

UK | FA-11331041 | February 2025
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