TeNET Study: Phase 2 Study to Assess Safety and Efficacy of Terbium-161 DOTATATE in Metastatic Neuroendocrine Tumors

Targeted radionuclide therapy is a nuclear medicine technique that uses radiopharmaceuticals with high affinity to receptors or antigens on the surface of tumor cells to achieve a therapeutic effect. TRT causes less collateral damage than external beam radiotherapy because the RPs are selectively taken up by tumors and their metastases  delivering high doses of radiation to cancer cells and minimizing doses to normal tissues. NETTER 1 and 2 trials have already established Peptide Receptor Radionuclide Therapy with Lutetium177 (DOTATATE as first line TRT in metastatic well differentiated gastroenteropancreatic neuroendocrine tumors. At Tata Memorial Hospital, we are routinely treating patients with PRRT with Lu 177 DOTATATE since 2019 and have completed nearly 700 cycles of PRRT till date. The superiority of Terbium 161 over Lu177 evolves from its basic property of emission of Auger electrons. Most important characteristics of radioisotopes in Nuclear Medicine or Radiation Oncology are linear energy transfer and range which are determinants of cell damage to the target cell and normal cell respectively. Compared to beta emissions as in Lu 177 AEs are most lethal to cancer cells when emitted near the cell nucleus and especially when incorporated into DNA. AEs cause DNA damage both directly and indirectly via water radiolysis. AEs can also kill targeted cancer cells by damaging the cell membrane and producing more targeted and lethal effects. Moreover, the important point is that since the range of delivery of this energy is relatively shorter as compared to beta-emitters, hence there is negligible bystander and crossfire effect, thereby causing no damage to surrounding cells. As of today Tb 161 DOTATATE is already commercially available in India and first therapy has already been administered, with multiple centers now starting this treatment.  Dept of Nuclear Medicine at Tata Memorial Center has already obtained approval from Atomic Energy Regulatory Board and has treated 2 patients of metastatic NET on compassionate basis with Tb 161 DOTATATE who were refractory to Lu 177 DOTATATE. We therefore would like to study the safety and efficacy of Tb 161 DOTATATE in patients in metastatic NET who have shown disease progression after treatment with Lu 177 DOTATATE PRRT.