[¹⁷⁷Lu]Lutetium-labelled PSMA ligand-induced remission in a patient with metastatic prostate cancer

Excerpt

The prostate-specific membrane antigen (PSMA) shows intense overexpression in the majority of prostate cancers (PCa) [1]. A Glu-urea-Lys motif has been found to bind with high affinity to the catalytic domain of PSMA [2]. Following conjugation to the chelator HBED-CC, a ⁶⁸Ga-labelled PSMA ligand (⁶⁸Ga-DKFZ-11) has been derived as a novel PET tracer [3]. Since PSMA is internalized after binding of a ligand [4], it is also an excellent target for systemic radionuclide therapy. Consequently, a ¹³¹I-labelled PSMA ligand (¹³¹I-MIP-1095) demonstrated favourable tumour-targeting properties and promising antitumour efficacy [5]. However, clinical application of ¹³¹I causes a high radiation burden and is hampered by complex regulations in most countries. Therefore, ¹⁷⁷Lu is considered to be preferable for targeted radionuclide therapy. The novel theranostic drug ¹⁷⁷Lu-DKFZ-617 is a DOTA derivative of the Glu-urea-Lys motif. The chelator is conjugated via an aromatic linker that further improves tumour accumulation while simultaneously reducing kidney uptake. …