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Peptide Receptor Radionuclide Therapy (PRRT)

Overview

PRRT is a targeted form of radionuclide therapy predominantly used in the treatment of neuroendocrine tumours (NETs). In this therapy, a radioactive moiety (commonly Lu-177, occasionally Ac-225) is combined with a biological molecule to specifically target the tumour receptors.  PRRT delivers targeted radiation directly to cancer cells, minimising side effects and improving the quality of life compared to conventional chemotherapy. 

The U.S. Food and Drug Administration (FDA) approved the PRRT in 2018, and it has since been used routinely in the clinical management of neuroendocrine tumours. Additionally, PRRT can also be used in somatostatin receptors (SSTR) expressing malignancies such as phaeochromocytoma, paraganglioma, neuroblastoma, lung carcinoid, medullary thyroid carcinoma, and meningioma.

Initially, PRRT was used only in the metastatic setting after progression on conventional therapy (usually octreotide). However, in the light of recent trials (NETTER-2), PRRT can be offered in the upfront setting as well. PRRT has known to prolong the progression free survival compared to conventional therapy (NEETTER 1 Trial). PRRT has been shown to significantly improve progression-free survival and alleviate symptoms (such as diarrhoea, gastritis, and hypoglycemic episodes) associated with neuroendocrine tumours.

PRRT is administered in the form of cycles, usually 4-6 with a gap of 10-12 weeks. Following two cycles, response evaluation is done with DOTA PET scan (FDG PET CT if required). Depending on the nature of the tumour, PRRT may be combined with somatostatin analogues or chemotherapy. 

  • DOTA PET CT scan as a part of prelude to PRRT, confirms the receptor expression status on the targeted lesions. FDG PET-CT can also be combined in a specific setting.
  • Lab tests: CBC, serum creatinine, LFT, and RFT to confirm the parameters are within the expected range.
  • ECOG / performance status
  • Comorbidities evaluation

  • Precautionary medications are administered, including antiemetics, steroids if necessary, and amino acid infusion to reduce renal toxicity.
  • Radionuclide therapy is administered slowly under the supervision of the Nuclear Medicine Physician with continuous monitoring of vitals. Therapies are administered only in designated wards approved by the regional radiation regularity body.
  • The total time taken for the therapy administration ranges from 4 to 6 hours. Depending on the patient's clinical status, the patient is discharged on the same or following day.

  • The most common immediate side effects of PRRT are nausea and vomiting, which are managed by pre-therapeutic antiemetic medications.
  • Rare side effects include carcinoid/catecholamine crisis, managed by proper pre-therapeutic evaluation, continuous monitoring of vitals during the therapy administration, and tackled accordingly with the antagonistic medications.  
  • Long-term side effects can occur, such as derangement of liver and kidney functions. However, monitoring the LFT and RFT before the therapy and in between the PRRT cycles can help the Nuclear Medicine Physician tailor the PRRT dose accordingly.
  • Transient suppression of RBC, WBC, and platelet counts can occur; however, the counts recover by the end of the month and are restricted to lower grades.

PRRT uses very small amounts of radiation. Over the next several days, the radionuclide will leave the body through urine and faeces. Patients are instructed to stay away from children and pregnant women for a few days. No other specific precautions post PRRT administrations are required.

  • Significant reduction of symptoms such as pain and hormone-related symptoms.
  • Reduction of disease burden on the PET CT scan or stability of the disease (stable disease is also considered a significant response as per international guidelines)
  • Improved quality of life
  • Improved progression-free survival
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