Diagnostic Imaging for Colon Carcinoma

Colon Carcinoma is the third most common malignancy in the world and the fourth leading cause of cancer-related death in the world, with 22% of patients presenting with the metastatic disease most in the liver and lung, which is the major cause of death.

The right-sided colon can be divided into cecum, ascending colon, and hepatic flexure, while the left-sided colon can be divided into splenic flexure, descending colon, sigmoid, and rectosigmoid. The molecular, embryological, biological, and anatomical features between right-sided (proximal) colon cancers and left-sided (distal) colon cancers and rectal cancers are quite different.

Fig.1 Differences in right-sided versus left-sided colon and rectum. (Dekker, E., et al., 2019, Lancet (London, England))

Diagnosis Approaches for Colon Carcinoma

• Clinical Symptoms

Patients with advanced-stage colon carcinoma can present with a wide range of symptoms, including occult or overt rectal bleeding, change in bowel habits, anemia, and abdominal pain, whereas patients with early-stage colon carcinoma show no significant symptoms.

• Endoscopy

Endoscopy is the first choice for colon carcinoma diagnosis, with significant identification of advanced lesions. However, in the early stage, colon carcinoma might appear as very subtle mucosal lesions. The colonoscope combined with adenoma detection can be used to re-assure the type of disease.

Fig.2 High-definition images of a flat and lateral-spreading polyp. (Dekker, E., et al., 2019, Lancet (London, England))

• Imaging

CT and PET-CT colonography are complementary imaging methods for the diagnosis of colon carcinoma. With MRI imaging at both local and whole body, the cancer stage and therapy methods can be confirmed, which is an essential step in cancer treatment.

• Laboratory Analysis

In addition to the analysis for a complete blood count, analysis of the carcinoembryonic antigen concentrations is recommended at the time of diagnosis, which is an elevated baseline in the postoperative phase.

• Pathology

Histology as the basis for pathological staging and subsequent management is widely applied in colon carcinoma diagnosis, such as the classic TNM staging, histological subtyping, grading, and histological assessment of lymphatic, perineural, and venous invasion, as well as a multitude of tumor-based markers.

Diagnostic Imaging for Colon Carcinoma with RDC

• The Targeted Molecule of Colon Carcinoma

CDCP1 (Complement C1r/C1s, Uegf, Bmp1 Domain-Containing Protein-1) is a type I membrane-spanning glycoprotein over-expressed on colon carcinoma cells. Mouse monoclonal 10D7 antibody chelated with Zirconium-89 can be utilized to bind the CDCP1 amino terminal for PET-CT-based detection.

• Imaging Result of ⁸⁹Zr-10D7

The newly discovered RDC (Radionuclide Drug Conjugate), ⁸⁹Zr-10D7, is composed of radioactive particle ⁸⁹Zr and 10D7, can be utilized into diagnostic imaging for colorectal cancer. Compared to the ⁸⁹Zr-IgG1κ control group, markedly higher activity was detected in tumors from mice administered ⁸⁹Zr-10D7. Combined with previous reports of elevated CDCP1 in colon carcinoma patient cohorts, the results of experiments in cell line xenograft and patient-derived models in mice indicate that the radio-labeled antibody agent, ⁸⁹Zr-10D7 can be employed in PET-CT imaging to detect colon carcinoma in vivo, as an aid to existing modalities of CT, MR, and FDG PET-CT imaging.

Fig.3 Representative 3D PET-CT imaging reconstructions of mice models administered agents. (Cuda, T. J., et al., 2021, Contrast media & molecular imaging)

References

1. Dekker, E., Tanis, P. J., Vleugels, J., Kasi, P. M., & Wallace, M. B. (2019). Colorectal cancer. Lancet (London, England), 394(10207), 1467–1480.
2. Cuda, T. J., He, Y., Kryza, T., Khan, T., Tse, B. W., Sokolowski, K. A., ... & Hooper, J. D. (2021). Preclinical Molecular PET-CT Imaging Targeting CDCP1 in Colorectal Cancer. Contrast media & molecular imaging.