BackgroundPancreatic ductal adenocarcinoma (PDAC) is a highly malignant solid tumor that lacks early diagnostic methods. Recently, targeted immunotherapy and radiotherapy have been integrated with radionuclide-antibody conjugate drugs, which can be used for targeted diagnosis and dynamic imaging of tumors. CEACAM6 is overexpressed in pancreatic tumors and is a potential theranostic target for PDAC. We aimed to develop a novel targeted carrier for theranostics of PDAC and other solid tumors.MethodsBased on camelid heavy-chain-only antibodies, we developed a CEACAM6-targeting recombinant antibody NY004, and evaluated it as a novel antibody-carrier for imaging and therapy of cancer in tumor models. We labeled NY004 with theranostic nuclides and applied this self-developed antibody platform in diagnostic imaging and antitumor assessment in PDAC models.ResultsThrough microPET, IHC, and biodistribution assays, targeting and biodistribution of [Zr-89]-NY004 in solid tumors including PDAC was examined, and the investigated tumors were all CEACAM6-positive malignancies. We found that NY004 was suitable for use as a drug carrier for radioimmunotheranostics. Our study showed that NY004 was characterized by high targeted uptake and a long retention time in PANC-1 tumors (up to 6 days post-injection), with good specificity and high imaging efficiency. Therapeutic evaluation of the radionuclide-labeled antibody drug [Lu-177]-NY004 in PDAC tumor-bearing model revealed that NY004 had high and prolonged uptake in tumors, relatively low non-target organ uptake, and good anti-tumor efficacy.ConclusionAs a drug platform for radiotheranostics, CEACAM6-specific antibody NY004 met the requirements of easy-labeling, targeting specificity, and effective persistence in pancreatic adenocarcinoma tissues.