Beyond PSMA: A Dual-Target Radioligand Takes Aim at FAP and αvβ3

Most radioligand therapies rely on a single molecular target. INN02 takes a different approach, combining two targets in the same molecule: fibroblast activation protein (FAP) and integrin αvβ3, both found in the tumour microenvironment. The same compound can be labelled with gallium-68 for PET imaging or lutetium-177 for therapy, creating a true theranostic platform.
In preclinical models, 68Ga-INN02 achieved tumour uptake of 11.65% of the injected activity per gram, compared with just 1.91% for the FAP-targeted comparator PNT6555. With lutetium-177, early tumour uptake reached 21.96% versus 12.98%, while exposure in blood and liver was lower. A single treatment significantly slowed tumour growth and increased median survival from in mice. A first small human imaging study involving six patients also showed clear uptake in primary and metastatic lesions across several cancer types.

Although prostate cancer was not the focus of the study, both targets are relevant to advanced disease. In a series of 116 castration-resistant prostate cancers, FAP was generally expressed at lower levels than PSMA, but among 19 PSMA-negative tumours, 58% remained FAP-positive. This suggests that FAP could provide an alternative target in at least some tumours that become poorly visible or potentially less treatable with PSMA-directed approaches.

Integrin αvβ3 may be particularly relevant in bone disease. In a small study of 12 men with metastatic prostate cancer, αvβ3-targeted 18F-Galacto-RGD PET detected 58 of 74 bone metastases, or 78.4%, although uptake varied considerably between patients and even between lesions in the same patient.
That heterogeneity is exactly where a dual-target strategy may have an advantage. A lesion with weak FAP expression may still express αvβ3, while another lesion may show the opposite pattern. Instead of relying on a single molecular doorway, INN02 attempts to use two.
The concept remains early and there is currently no evidence that INN02 can treat prostate cancer. But the study provides a useful proof of principle.

Source.