This Article is a sum of a discussion with Dr. Ishita B Sen (Director and Head of the Department of Nuclear Medicine & Molecular Imaging at Fortis Memorial Research Institute (FMRI), Gurgaon).
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:
- 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.
- Alpha particles have a very high Linear Energy Transfer (LET) value, which enables them higher molecular damage per unit length of the tumour cells. Beta Particles, on the other hand, have a lower range of LET which requires a much higher accumulation compared to Alpha Particles for similar molecular damage to tumour cells.
- High LET radiation results in more severe and less reparable cell damage than low-LET radiation, alpha particles create a high ionisation density, which causes a high number of double-strand breaks as compared with beta particles which have a lower ionisation density - this caused irreparable DNA damage to the tumour cells.
In addition to Neuroendocrine tumours, there have been various studies which have examined the effects of TATs on other cancers including prostate, NET, breast, colon, myeloma, and ovarian cancer. Of these, prostate cancer is attracting the most interest. PSMA is the target overexpressed in prostate cancers. 177Lu-PSMA therapies have become an established treatment for patients with progressive metastatic prostate cancer. However, more recently there have been publications by German and South African groups describing the benefit of TAT.
Also Read: Which Patients can benefit with PRRT?
Also Read: Is PRRT Safe for you?
For more information on Targeted Alpha Therapy please write Dr. Ishita B Sen Email: firstname.lastname@example.org
This article has been written using the below-published paper as a reference.
Targeted Alpha Particle Therapy for Neuroendocrine Tumours: The Next Generation of Peptide Receptor Radionuclide Therapy
Shaunak Navalkissoor and Ashley Grossman
Department of Nuclear Medicine, ENETS Centre of Excellence, Royal Free Hospital, London, UK; b NET Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK