@article {Cullinane315, author = {Carleen Cullinane and Charmaine Jeffery and Rachael Walker and Peter Roselt and David Binns and Ellen van Dam and Matthew Harris and Paul Donnelly and Rodney Hicks}, title = {Comparing the therapeutic efficacy of 67Cu-SARTATE and 177Lu-DOTA-octreotate in a neuroendocrine tumor model}, volume = {59}, number = {supplement 1}, pages = {315--315}, year = {2018}, publisher = {Society of Nuclear Medicine}, abstract = {315Objectives: Peptide receptor radionuclide therapy (PRRT) using radiolabeled octreotate is an effective treatment for somatostatin receptor 2 (SSTR2) expressing neuroendocrine tumors (NET). The diagnostic and therapeutic potential of the copper isotopes, Cu-64 and Cu-67, respectively, offers the possibility of using a single SSTR2 targeted peptide conjugate as a theranostic agent.64Cu-SARTATE, consisting of a bifunctional chelator, MeCOSar, conjugated to (Tyr3)-octreotate, was successfully trialled as an imaging agent and potential prospective dosimetry tool in ten patients with NETs. The aim of this study was to explore the antitumor efficacy of 67Cu-SARTATE in a preclinical model of NET and compare it with that of the standard PRRT agent, 177Lu-DOTA-octreotate (177Lutate). Methods: AR42J rat neuroendocrine cells were implanted subcutaneously into Balb/c nude mice. Once the tumors reached a volume of approximately 150mm3 the mice were randomized into treatment groups of 7 animals to receive saline, 177Lutate or 67Cu-SARTATE via intravenous injection. Tumor volumes were measured twice weekly and animals euthanized once tumors reached a volume \>1200 mm3. Tumor growth was analysed by ANOVA followed by Dunnett{\textquoteright}s post-hoc test while Kaplan Meier survival curves were analysed using the Mantel Cox log rank test. Results: On day 7 following a single administration of 5 or 20 MBq 67Cu-SARTATE AR42J tumor growth was inhibited by 75\% and 78\% respectively (P= 0.0001 for both groups vs control) while 5 and 25 MBq 177Lutate inhibited tumor growth by 89\% and 100\%, (P\<0.0004 for both groups vs control), respectively. Survival, defined as time to tumor volume greater than 1200 mm3, was extended from 12 days in the control group to 21 and 26 days following 5 and 20 MBq 67Cu-SARTATE, respectively (P\<0.001) and 21 and 29 days following 5 and 25 MBq 177Lutate (P\<0.001). All treatments were well tolerated where reduction in animal body weight from baseline was transient and did not exceed 5 \%. 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, significantly improved survival when compared to delivery as a single fraction (67Cu-SARTATE: 46 vs 35 days; P= 0.04; 177Lutate: 46 vs 29 days; P=0.04). Furthermore, the efficacy of 67Cu-SARTATE and 177Lutate was equivalent on both treatment schedules (P = n.s.). Conclusions: 67Cu-SARTATE is well tolerated in Balb/c nude mice and highly efficacious against AR42J tumors in vivo. Administration of 67Cu-SARTATE and 177Lutate divided into two fractions over two weeks was more efficacious than that of a single fraction. The antitumor activity of 67Cu-SARTATE in the AR42J tumor model was equivalent to that of 177Lutate, demonstrating the suitability of this novel agent for clinical assessment in the treatment of SSTR2 expressing NET.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/59/supplement_1/315}, eprint = {https://jnm.snmjournals.org/content}, journal = {Journal of Nuclear Medicine} }