FAPi-based targeted theranostics for treating radioiodine-refractory differentiated thyroid cancer
The study of FAPi-based lutetium-177 therapy in the All India Institute Of Medical Sciences in New Delhi was meant to investigate the therapeutic efficacy and safety of 177Lu-DOTAGA.(SA.FAPi)2 in RR-DTC patients. 15 heavily pre-treated (min 2 lines of prior treatment with lenvatinib and/or sorafenib) patients with the disease progression were selected based on FAPi PET/CT. An average of 3 sessions of 2 GBq each was administered in an 8-week interval.
The results were quite promising. Thyroglobulin Tg levels fell in all probands. Partial response was documented in 4 patients and progression stopped in 3 of them. All patients reported pain relief and a decrease in the intake of analgesics.
No serious side effects were reported. The colon demonstrated the highest undesirable uptake. Although there is no evidence supporting fatty diet and laxatives to accelerate the excretion, the scientists did include them in the regimen.
Despite its small sample, the study demonstrated the efficacy and safety of the treatment as well as tumour retention times of up to 6 days necessary for the beta-emitter to produce the desired impact. The cumulative doses administered were relatively low and can be increased according to the maximum safe limit of radiation dose to the colon as the most exposed organ.
You will find the scientific paper in full here.
It had been discovered that tumour microenvironment sustains and promotes progression of many cancer types. Common among solid tumours is the presence of Cancer-Associated Fibroblasts (CAFs) in the tumour microenvironment. CAFs stand out for the abnormally high expression of Fibroblast Activating Proteins (FAPs) in them. Targeting CAFs with FAP inhibitors (FAPi) aims to destroy the microenvironment and to interfere with its sustaining and protecting function thereby exposing the cancer cells to the forces of the body’s own immune system as well as to various therapies.
FAPi molecules labelled with gallium-68 are being successfully used for imaging purposes. The complexity of creating a molecule for therapeutic purposes (to be labelled with beta- or alpha-emitters) consisted in its early tumour washout, what limited the therapeutic efficacy of the emitters. With the development of a dimer DOTAGA.(SA.FAPi)2, Johannes Gutenberg University of Mainz managed a decisive leap.
You can read more about FAPi here.