Dimeric FAP Radioligand 177Lu-D7ND Reaches Its First Five Patients After Complete Remissions in Xenografts

Two Cell Lines, Two Different Jobs

Yang Liang is first author and Bing Jia of the Medical Isotopes Research Center at Peking University and Ru Gao of the nuclear medicine department at the First Affiliated Hospital of Xi'an Jiaotong University are the corresponding authors. The preclinical package rests on U-87 MG glioblastoma cells and on HT1080 fibrosarcoma cells engineered to carry human FAP, the second of which supplies a defined target density that the first does not. Competitive and saturation binding assays established affinity and selectivity for FAP, biodistribution and imaging showed high specific uptake in FAP-positive tumors, and clearance ran through the kidneys with little accumulation elsewhere. The authors put their reason for choosing the target simply, calling FAP attractive for radiopharmaceutical development because its expression is restricted to tumor.

Sixteen authors signed the paper, spread across the departments a precursor must pass through before it reaches a patient. Nuclear medicine at the First Affiliated Hospital of Xi'an Jiaotong University supplies most of the names, oncology at the same hospital contributes two, Peking University's Medical Isotopes Research Center and Department of Radiation Medicine supplies the corresponding chemist, and a further author works at the Minnan PET Center and the Xiamen Key Laboratory of Radiopharmaceuticals at the First Affiliated Hospital of Xiamen University.

Considerable tumor washout happened inside 24 hours, though activity associated with tumor was still detectable at 48 and 72 hours. Tumor growth inhibition was dose-dependent, and at 55.5 megabecquerels a subset of the HT1080-hFAP animals cleared entirely, with no significant weight loss and no organ toxicity noted.

Stable Disease in Three of Four Evaluable Patients

Five patients with FAP-positive breast or non-small cell lung cancer received therapeutic 177Lu-D7ND. Imaging in those patients matched the animal work at the front end, with intense initial tumor uptake, and diverged from it at the back end, with measurable tumor retention still visible on delayed scans at seven days and nothing notable in critical organs. Stable disease was the outcome in three of the four patients who could be evaluated after a single cycle, and the authors record minimal adverse effects.

Liang and colleagues set the limit themselves, describing their clinical result as preliminary data on pharmacokinetics and short-term tolerability in a small pilot cohort. The abstract published with the paper is the only version available without a subscription, and it does not give injected activity per patient, the dosimetry estimates for tumor or organs, or how FAP positivity was established before treatment.

Why This Matters to the APO|APE Reader

Tianyu Liu, one of the 16 authors, is an employee of Pharmadax Genesis Pharmaceutical Technology in Beijing, and that employment is the only competing interest declared on the paper, which places a commercial sponsor beside a five-patient result. The regulatory distance still to cover is visible in the two lutetium-177 therapies already on the U.S. market. Drugs@FDA records Lutathera, targeting the somatostatin receptor, approved under priority review on January 26, 2018, and Pluvicto, targeting PSMA, approved as a new molecular entity on March 23, 2022, each arriving with a companion imaging agent and a defined patient selection step. FAP has neither of those settled, which is the gap a dimeric ligand with seven-day tumor retention is being built to close.