Advancements in PRRT for treating Neuroendocrine tumours and other cancers. A look at Targeted Alpha Therapy

 Neuroendocrine tumours (NETs) are heterogeneous with varying behaviour. Treatment decisions are taken basis Histological studies plus imaging data and clinical studies. Surgery is a curative option for NET patients with localized well-differentiated tumours, for non-localized metastatic tumours, Surgery is not an option.

PRRT (Peptide Receptor Radionuclide Therapy) is a curative option for non-localised, heterogeneous, metastatic neuroendocrine tumours. PRRT has proven to be the most promising treatment modality amongst various systemic treatments such as Somatostatin Analogues, Chemotherapy, Molecular Targeted Treatments, Alpha Interferon etc. PRRT causes DNA damage to the tumour cells.

In the 1990s PRRT was administered using the radiopeptide 111In-DTPA-octreotide (Octreoscan®), the responses were reasonable but the effects were not long-lived and there were long term adverse sequelae.

Next PRRT agent to be developed was the more effective beta-emitting radionuclide Y90, sustained symptomatic and objective responses with 90Y-PRRT were frequently observed, but it also led to significant renal damage. The renal toxicity is related to reabsorption of the radiopeptide in the proximal tubules, with the long path length of the 90Y beta particle imparting a significant absorbed dose to the radiosensitive glomeruli.

Lutetium 177 was the next PRRT radiopharmaceutical to be developed, it is one of the most widely used PRRT agents even today. Lu 177 therapy led to prolonged progression-free survival for the patients and a low degree of renal toxicity compared to 90Y PRRT. 

 There have been significant advancements in optimising the effectiveness of PRRT, some of these include the introduction of intra-arterial treatments (especially effective in treating Liver Metastases), usage of dosimetry to assess the uptake of the radio peptide, combining of Lu 177 DOTATATE and 90Y PRRT to target large and small tumours, using chemotherapy as a PRRT radiosensitiser, a somatostatin receptor (SSR) antagonist PRRT and targeted alpha-particle therapy (TAT). 

Targeted Alpha Therapy has been gaining popularity and acceptance over the last few years, there are some advantages of Targeted Alpha Therapy versus Beta Particle Therapy, these are enlisted below:

Read more at Advancements in PRRT for treating Neuroendocrine tumours and other cancers.
A look at Targeted Alpha Therapy

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