Procedural details:
For this report and presentation,
various clinical trials conducted under the Neuroendocrine Tumours Therapy Trials (NETTER) and current ongoing trials for the treatment of mCRPC were reviewed.
See table 2 for a list of reviewed clinical trials.
In addition,
research articles reviewed as listed in the reference,
were accessed using search tools such as PubMed and Google scholar and relevant keywords (NET clinical trials,
PRRT,
Lu-177 labelled PSMA-617 outcomes).
Characteristics of an ideal theranostic radionucleotide:
Ø It must emit gamma and beta radiation as gamma helps in diagnosis while beta would be helpful for therapy purposes.
Ø The half-life of the radionuclides used for the therapy purposes must be long enough to be suitable for transportation without losing therapeutic potency.
Ø The level of mean beta radiation penetration of the agent must be adequate to enable targeting the metastatic cells and minimising the exposure of surrounding healthy cells to the penetrating radiation.
Ø Radionuclides must have a chemical structure which is compatible for labelling with various customised pharmaceutical molecules in order to target cancer cells.
Ø Radionuclide should not adversely affect normal physiological processes.
It is also essential that it should have a shorter biological half-life so that it can be cleared from the system quickly(Yeong,
Cheng,
& Ng,
2014).
Mechanisms by which theranostic radionuclides target cancer cells:
Radionuclide therapy targets the cancer cells by various mechanisms.
These mechanisms,
listed in table 3,
are crucial for both diagnostic and therapeutic purposes.
Properties of Lutetium-177:
More than 100 radioisotopes are currently being used or are eligible to be used for theranostic purposes(Dash et al.,
2013).
Most commonly used are Iodine-131 (I131),
Lu177 and Yttrium-90(Y90) (as listed in table 1).
Although Lutetium-177 radioactive isotope which is a late entrant in the field of radionuclide therapy,
it is showing promising results as a theranostic agent (Banerjee,
Pillai,
& Knapp,
2015).
Please see table 4 for specific properties of Lu -177.
Characteristics which make Lutetium a better choice for theranostic purposes:
Ø It has +3 oxidation states; this chemical structure makes it a favourable ligand for various therapeutic agents (Banerjee et al.,
2015).
Ø Long enough half-life of 6.73 days which makes it easy to transport without losing its therapeutic potency (Banerjee et al.,
2015).
Ø The mean penetration ranges of beta particles emitted by Lu177 in soft tissue is 670-micron meter.
This characteristic is helpful in delivering energy to small volumes,
such as micrometastatic disease and near the surface of tumour cells (Banerjee et al.,
2015).
Ø Due to its maximum penetration of 2mm limit,
it is possible to effectively localise the cytotoxic radiation to relatively small areas with Lu177.
This enables the efficient destruction of small tumours and metastatic lesions with less damage to surrounding healthy tissue (Banerjee et al.,
2015).
Carrier-aided (CA),
and Non-Carrier aided (NCA) Lu-177 production methods:
Radioisotope Lu-177 is produced in a nuclear reactor by two methods.
Based on the production methods it is called either as a carrier aided (CA) or no-carrier aided (NCA). NCA is most commonly used in current practices as does not produce any co-product which serves as a radionuclide impurity.
In addition,
it produces the highest yield in labelling methods.
Differences between CA and NCA have been displayed in table 5.
Commonly available Lu-177 labelled radiopharmaceuticals:
There are various Lu-177 labelled radiopharmaceuticals available and currently being used (See Table 6).
Most commonly used labelled pharmaceuticals with promising results are Lu-177 DOTATATE and DOTA-TOC.
These are being used for the treatment of Neuroendocrine tumours (NETs).
Lu-177 labelled PSMA is also currently under trial to treat the metastatic prostate cancer.
Most of the listed Lu-177 labelled radiopharmaceuticals are proving to be very helpful in improving the quality of life for the patients.
Highlights from the reviewed articles and clinical trials:
Ø The reviewed clinical trials and research articles) found Lu-177 as an effective agent for improving the quality of life and progression-free survival in the affected patients.
Ø Lu-177 labelled radiopharmaceuticals principally DOTA-TATE,
and DOTA-TOC has shown promising results in treating the poorly differentiated Neuroendocrine Tumour (NET) by improving quality of life for the patients (By reducing body pain,
showing improved appetite and improvement in the weight).
Quite a few studies reported improved quality of life treated with Lu-177-DOTATATE/TOC (Basuroy et al.,
2018; Khan et al.,
2011; Strosberg,
2017).
Ø Lu-177 labelled PSMA is also showing promising results for the metastatic prostate cancer disease.
Khan et al.
(2011) reported significantly improved quality of life in prostate cancer patients treated with Lu-177 labelled therapeutic agents.
Ø Lu-177 labelled DOTA-TAT and DOTA -TOC deliver radiation exposure to metastatic cells,
bring the biochemical activity down,
and their activity increases with the number of cycles of selected doses delivered.
So far,
no side effects have been noticed; in addition,
doses can be customized as per the disease condition/s.
Ø Lu-177 labelled EDTMP and Rituximab are also showing excellent results in the currently ongoing trial for the breast cancer and for treating non-Hodgkin lymphoma.
Lu-177-CC49 which is currently being trialled for the ovarian cancer is also showing promising results (Alvarez,
Partridge,
Khazaeli,
et al.,
1997).