ADVANCEMENTS IN PRRT FOR TREATING NEUROENDOCRINE TUMOURS AND OTHER CANCERS. A LOOK AT TAT
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:
1. Alpha particles have
higher energy than Beta particles and have a short therapeutic range. This
helps impart higher energy to the nuclei of the tumour cells and ultimately
damaging them, since the energy is higher than Beta Particles, Alpha therapy
also called the Magic Bullet Therapy. The range of alpha particles is
equivalent to the thickness of 1-3 cell widths, due to this short therapeutic
range alpha particles better target and damage the tumour cells.
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