TLX101 (formerly ACD-101) is a small molecule (4-Iodophenylalanine), radioactively labeled with either 123I for SPECT imaging, 124I for PET imaging or 131I for therapy. These molecules target glioma. Orphan drug status for glioma diagnosis was granted to 123I-ACD-101 by EMA on July 27, 2006. Orphan drug status for glioma therapy was granted to 131I-ACD-101 on April 11, 2006 by the EMA and on January 4, 2011 by the FDA. All molecules have been acquired by Telix Pharmaceuticals Ltd. in January 2017.
TLX-101 is a cytostatic molecule with an intrinsic radio-sensitizer effect, increasing the biological effect of external field radiation (current standard therapy for brain tumors). When radiolabeled with 131I the molecule conveys an intracellular toxic effect. TLX-101 easily crosses the intact blood–brain barrier into tumor tissue where it is retained for several days. Intratumoral accumulation of TLX-101 occurs independently from histological tumor type in low- and high-grade gliomas alike (WHO grades II–IV).
In parallel with radiotoxicity, TLX-101 shows a radiosensitizer effect and a cytostatic effect.
123I-TLX-101 and 131I-TLX-101 have entered Phase I clinical trials. 123I-TLX-101 has been successfully evaluated in over 100 patients. The first patient with recurrent progressive low grade glioma treated with 2 GBq (54 mCi) 131I-TLX-101 showed a sustained reduction of tumor volume. The patient was still alive 3.5 years after first treatment and no further treatment option.
Treatment of glioma patients with combination of RT and 131I-TLX-101 is also under way.
A phase I/II study to systematically evaluate XRT + 131I TLX-101 combination therapy in patients with recurrent GBM is currently in preparation, in collaboration with leading European neuro-oncology institutions. A further phase I study to investigate 124I TLX-101 as a proprietary PET tracer for diagnosis, therapy planning, and follow-up of glioma is about to start.