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An estimated 25% of patients with colorectal cancer (CRC) present with distant metastases at the time of diagnosis, the most common site being the liver. Controversy exists regarding the safety of a simultaneous versus staged approach to resections in these patients, but reports have shown that minimally invasive surgery (MIS) approaches can mitigate morbidity. This is the first study utilizing a large national database to investigate colorectal and hepatic procedure-specific risks in robotic simultaneous resections for CRC and colorectal liver metastases (CRLM). Utilizing the ACS-NSQIP targeted colectomy, proctectomy, and hepatectomy files, 1,550 patients were identified who underwent simultaneous resections of CRC and CRLM from 2016–2020. Of these patients, 311 (20%) underwent resections by an MIS approach, defined as an either laparoscopic (n = 241, 78%) or robotic (n = 70, 23%). Patients who underwent robotic resections had lower rates of ileus compared to those who had an open surgery. The robotic group had similar rates of 30-day anastomotic leak, bile leak, hepatic failure, and post operative invasive hepatic procedures compared to both the open and laparoscopic groups. The rate of conversion to open was significantly lower for robotic compared to laparoscopic group (9% vs. 22%, p = 0.012). This report is the largest study to date of robotic simultaneous CRC and CRLM resections reported in the literature and supports the safety and potential benefits of this approach.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose and has dismal survival rates. Molecular imaging techniques such as positron emission tomography (PET) could fulfill an unmet need and enable an early diagnosis of PDAC to potentially improve survival. EphA2, a member of Erythropoietin-producing hepatocellular (Eph) receptors, plays a pivotal role in the tumorigenesis and development of an immune suppressive microenvironment in PDAC. We therefore developed a peptide-based PET imaging agent for EphA2, [68Ga]AJ201, and evaluated its pharmacokinetics and potential to non-invasively quantify variable EphA2 expression in PDAC. Methods: A Gallium-68 labeled EphA2 binding peptide, [68Ga]AJ201, was synthesized in high radiochemical yields and purity. Surface plasmon resonance (SPR) analysis was carried out to measure binding affinity. EphA2 expression was assessed in PDAC cell lines and tissues in CCLE and TCGA. EphA2 expression in seven PDAC cell lines (Panc1, AsPC1 BxPC3, CFPAC1, Hs766T, Panc1005, and SU8686) was validated by RT-qPCR and flow cytometry. Those cell lines were then used for in vitro binding assays and the corresponding xenografts in NSG mice for PET imaging and ex vivo biodistribution studies (n=4-5/tumor). Specificity of [68Ga]AJ201 was confirmed by co-injection of a blocking dose of non-radioactive AJ201 (1 mg/kg). Results: SPR analysis showed that AJ201 binds EphA2 with a high affinity (KD) of 0.2 nM. TCGA analysis revealed higher expression of EphA2 in PDAC vs healthy tissues. Flow cytometry analysis revealed high and variable EphA2 expression in all the PDAC cell lines tested with Panc1 exhibiting the highest levels. In vitro binding assays showed high and variable [68Ga]AJ201 uptake in all the PDAC cell lines and low uptake in the presence of 1µM non-radioactive AJ201 and in EphA2 negative Jurkat cells. Pharmacokinetics of [68Ga]AJ201 in mice with Panc1 tumors showed high contrast images of EphA2 expression at 60 minutes with a tumor/muscle ratio of 25.9±6.7. That high tumor uptake was significantly reduced in mice receiving blocking dose confirming the specificity of the radiotracer. Also, [68Ga]AJ201 PET quantified variable EphA2 expression in all the seven PDAC xenografts tested, with highest uptake observed in Panc1 tumor, followed by SU8686, and lowest in CFPAC1. Ex vivo biodistribution studies corroborated PET imaging findings. Conclusion: [68Ga]AJ201 is a EphA2 specific high affinity peptide-based PET imaging agent that provides high contrast PET images of PDAC by 60 minutes. [68Ga]AJ201 PET has the potential to non-invasively detect PDAC in patients. Citation Format: Kuldeep Gupta, Ajay Kumar Sharma, Akhilesh Mishra, Sophia Y. Chen, Gabi Lofland, Todd M. Armstrong, Lei Zhang, Elizabeth M. Jaffee, Sridhar Nimmagadda. Imaging pancreatic ductal adenocarcinoma using an EphA2 receptor tyrosine kinase binding 68Ga-labeled peptide radiotracer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2481.