First-in-human CLDN18.2 functional diagnostic pet imaging of digestive system neoplasms enables whole-body target mapping and lesion detection

Screening, Construction, and Preliminary Evaluation of CLDN18.2-Specific Peptides for Noninvasive Molecular Imaging

“…As a first in human CLDN18.2 PET tracer, 124I-18B10(10L) can clearly show most of the lesions overexpressing CLDN18.2 (NCT04883970). 42 However, importantly, (1) the production cost of humanized monoclonal antibodies is high, (2) long half-life nuclides are relatively scarce and cannot be mass-produced, (3) multiple imaging cycles within a week, and the resulting high radiation exposure to patients and staff, and (4) the high uptake of nanobodies in the kidneys and the high uptake of whole-antibody probes in the liver and spleen reduce their diagnostic value for lesions in the above organs. All of the above reasons hinder the clinical transformation of this type of probe.…”

68Ga-NC-BCH Whole-Body PET Imaging Rapidly Targets Claudin18.2 in Lesions in Gastrointestinal Cancer Patients

“…68 Ga-NC-BCH was taken up strongly by the gastric mucosa in a mouse model, indicating that the smaller molecular architecture allows it to reach the insidious and dense CLDN18.2 epitope on the gastric mucosa. However, since CLDN18.2 is typically buried in the gastric mucosa, neither of the previous monoclonal antibody-based probes— 89 Zr-DFO-TST001 and 124 I-18B10(10L)—was available in normal tissue ( 9 , 15 , 16 ). In addition to gastric organ and positive tumors, probes have a high nonspecific radioactive accumulation in the kidneys, as previously reported ( 17 ).…”

“…Immunohistochemistry is an invasive process that covers only a small amount of tissue and does not reflect the heterogeneity of CLDN18.2 expression within the tumor. Previously, we reported the first—to our knowledge—clinical results of the 124 I-labeled CLDN18.2 humanized monoclonal antibody 124 I-18B10(10L), which showed that CLDN18.2 can be detected in tumor lesions ( 9 ). However, the large molecular weight of the monoclonal antibodies results in a long imaging cycle that cannot be completed in a day.…”

Antibody-mediated targeting of Claudins in cancer

“…These observations reveal a clear therapeutic window, which has accelerated the translation of various strategies to target these particular proteins into clinical trials. Moreover, these markers have not only been used as targets for drug delivery, but can also be exploited for diagnostic applications, such as imaging (139). Based on the promising results achieved thus far with CLDN6 and CLD18.2, there will be continued interest in exploring additional claudin family members that are emerging as important targets in different stages of tumor growth and metastatic progression.…”