Evaluation of novel anti-CEACAM6 antibody-based conjugates for radioimmunotheranostics of pancreatic ductal adenocarcinoma.
Eur Radiol
; 33(10): 7077-7088, 2023 Oct.
Article
en En
| MEDLINE
| ID: mdl-37166496
ABSTRACT
BACKGROUND:
Pancreatic 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.METHODS:
Based 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.RESULTS:
Through microPET, IHC, and biodistribution assays, targeting and biodistribution of [89Zr]-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 [177Lu]-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.CONCLUSION:
As a drug platform for radiotheranostics, CEACAM6-specific antibody NY004 met the requirements of easy-labeling, targeting specificity, and effective persistence in pancreatic adenocarcinoma tissues. KEY POINTS ⢠[89Zr]-NY004 has good specificity and high imaging efficiency, and is characterized by high tumor-targeting uptake and a long tumor retention time as a PET molecular imaging tracer. ⢠Therapeutic radionuclide-conjugated antibody drug [177Lu]-NY004 has high uptake and prolonged uptake duration in tumors, low non-target organ uptake, and significant tumor-inhibiting efficacy in PDAC model. ⢠The self-developed antibody structure NY004 is a promising drug platform for radioimmunotheranostics of CEACAM6-positive tumors including pancreatic ductal adenocarcinoma.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
/
Adenocarcinoma
/
Carcinoma Ductal Pancreático
Límite:
Humans
Idioma:
En
Revista:
Eur Radiol
Asunto de la revista:
RADIOLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China