Evaluation of 131I-Anti-Angiotensin II Type 1 Receptor Monoclonal Antibody as a Reporter for Hepatocellular Carcinoma

Abstract

BackgroundFinding a specific agent is useful for early detection of tumor. Angiotensin II type 1 receptor (AT1R) was reported to be elevated in a variety of tumors and participate in tumor progression. The aim of our study was to evaluate whether 131I-anti-AT1R monoclonal antibody (mAb) is an efficient imaging reporter for the detection of hepatocellular carcinoma.Methodology/Principal FindingsAT1R mAb or isotype IgG was radioiodinated with 131I and the radiochemical purity and stability of the two imaging agents and the affinity of 131I-anti-AT1R mAb against AT1R were measured. 3.7 MBq 131I-anti-AT1R mAb or isotype 131I-IgG was intravenously injected to mice with hepatocellular carcinoma through tail vein, and then the whole-body autoradiography and biodistribution of the two imaging agents and the pharmacokinetics of 131I-anti-AT1R mAb were studied. 131I-anti-AT1R mAb and 131I-IgG were successfully radioiodinated and both maintained more stable in serum than in saline. The 131I-anti-AT1R mAb group showed much clearer whole-body images for observing hepatocellular carcinoma than the 131I-IgG group. The biodistributions of the two imaging agents suggested that hepatocellular carcinoma tissue uptook more 131I-anti-AT1R mAb than other tissues (%ID/g = 1.82±0.40 and T/NT ratio = 7.67±0.64 at 48 h), whereas hepatocellular carcinoma tissue did not selectively uptake 131I-IgG (%ID/g = 0.42±0.06 and T/NT ratio = 1.33±0.08 at 48 h). The pharmacokinetics of 131I-anti-AT1R mAb was in accordance with the two-compartment model, with a rapid distribution phase and a slow decline phase. These results were further verified by real-time RT-PCR, immunohistochemistry staining and Western blot.Conclusions/Significance 131I-anti-AT1R mAb may be a potential target for early detection of tumor.

Angiotensin-(1–1) Suppresses Hepatocellular Carcinoma Growth and Angiogenesis via Complex Interactions of Angiotensin II Type 1 Receptor, Angiotensin II Type 2 Receptor and Mas Receptor

“…Our results indicated that Ang-(1-7) arrested the proliferation of tumor cells by downregulating AT 1 R and upregulating AT 2 R and MasR. Overexpression of AT 1 R has been demonstrated in a variety of tumors in vitro and in vivo, such as hepatocellular carcinoma and breast and ovarian cancer (7,20,21). AT 1 R induces tumor cell proliferation by two main intracellular mechanisms: AT 1 R activates phosphatidylinositol, utilizes two main second messengers, triphosphoinositol and diacylglycerol and causes an increase in cytosolic Ca 2+ content, a process linked to mitogenesis in several cell types (22); and AT 1 R modulates the activity of protein tyrosine kinases, which are coupled to the receptors of several growth factors and are involved in the transduction of growthinducing signals.…”

“…Although the literature supports a beneficial role for Ang-(1-7) in lung cancer and prostate cancer (5,6), the effects of Ang-(1-7) on other tumors have not been evaluated. We recently confirmed that AT 1 R was overexpressed in hepatocellular carcinoma tissue using a murine H22 hepatoma model (7). Which receptor of Ang-(1-7) is activated to mediate its effects is much speculated.…”

Angiotensin II type I receptor (AT1R) is an independent prognosticator of esophageal squamous cell carcinoma and promotes cells proliferation via mTOR activation

“…The relationship between the use of AT1R blockers and cancer risk has drawn significant attention since 2010 [ 18 ]. Accumulating evidence has shown that AT1R blockers are associated with decreased risks of colorectal cancer, lung cancer, and prostate cancer [ 19 , 20 ]. However, some studies have also found that there is no significant association between the use of AT1R blockers and other human cancers, such as liver, gastric, and hematological malignancies [ 16 , 21 ].…”

Recent Advances in Hepatocellular Carcinoma Treatment with Radionuclides

“…HCC-targeted antibodies labeled with 131 I have been intensively studied for the treatment of HCC, with the most common antibodies including mouse anti-human monoclonal antibody fragment HAb18F(ab) 2 (metuximab), ChTNT human-mouse chimeric antibody, hepama-1 HCC cell membrane monoclonal antibody, CD133 monoclonal antibody, anti-hepatitis B virus antibodies, anti-machine protein monoclonal antibody, and anti-human HCC transferrin monoclonal antibody. Radioimmunotherapy agents used for HCC with clinical trials include 131 I-metuximab, 131 I-chTNT, and 131 I-hepama-1 monoclonal antibody [76,77].…”

“…131 I acts to treat the surrounding tumor cells, causing new necrosis, while the chTNT monoclonal antibody expands to the newly necrotic area to continuously expand it to achieve the therapeutic goal. At present, 131 I-chTNT is considered to have a therapeutic effect on lung cancer, brain cancer, and liver cancer, among others [76,80].…”