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 in 2006. Orphan drug status for glioma therapy was granted to 131I-ACD-101 in 2006 by the EMA and in 2011 by the FDA.

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).

123I-TLX-101 and 131I-TLX-101 have entered Phase I clinical trials. 123I-TLX-101 has been successfully evaluated in over 100 patients. 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. By September 2018, an international multi-center, open-label phase I/II dose ranging study to evaluate the safety, tolerability, dosing schedule and preliminary efficacy of 131I-TLX101 was initiated in patients with recurrent glioblastoma multiforme in conjunction with external radiotherapy (XRT) (clinical trial design IPAX-1). Enrollment is expected to be completed by end of 2020 and study to be completed by end of 2021.

Target/Mechanism: LAT-1

Leading Emitter: beta electrons (β–)