PRRT using radiolabelled octreotate is an effective treatment for SSTR2-expressing NETs. Given the diagnostic and therapeutic potential of the copper isotopes, Cu-64 and Cu-67, respectively, we are developing a novel SSTR2 targeting conjugate as a theranostic agent. 64Cu-SARTATE has been successfully trialled as an imaging agent and potential prospective dosimetry tool in NET patients. As the therapeutic effects of this agent are yet to be determined, the aim of this study was to explore the efficacy of 67Cu-SARTATE in a preclinical model of NET and compare it with that of 177Lu-DOTA-octreotate (177Lutate).
Mice bearing AR42J xenografts were randomized into treatment groups to receive saline, 177Lutate or 67Cu-SARTATE via intravenous injection. Tumour volumes were measured twice weekly and percentage tumour growth inhibition (TGI) was calculated. Kaplan Meier survival curves were analysed using the Mantel Cox log rank test.
All treatments were well tolerated. Dose dependent TGI was observed after single administrations of 67Cu-SARTATE and 177Lutate. Survival was extended from 12 days in the control group to 21 and 26 days following 5 and 20 MBq 67Cu-SARTATE, and 21 and 29 days following 5 and 25 MBq 177Lutate. In a second study, the efficacy of fractionated delivery of PRRT was assessed. Administration of a total of 30 MBq 67Cu-SARTATE or 177Lutate as two 15 MBq fractions two weeks apart improved survival compared with that when delivered as a single fraction (67Cu-SARTATE: 47 vs 33 days; 177Lutate: 46 vs 29 days). Furthermore, the efficacy of 67Cu-SARTATE and 177Lutate was equivalent on both treatment schedules.
In conclusion, fractionated administration of 67Cu-SARTATE and 177Lutate was more efficacious than a single fraction. The efficacy of 67Cu-SARTATE in the AR42J tumour model was equivalent to that of 177Lutate, demonstrating the suitability of this novel agent for clinical assessment in the treatment of SSTR2 expressing NETs.