Cerenkov luminescence imaging is an effective preclinical tool for assessing colorectal cancer PD-L1 levels in vivo

Abstract

Background : Preclinical and clinical studies have demonstrated that immunotherapy has effectively delayed tumor progression, and the clinical outcomes of anti-PD-1/PD-L1 therapy were related to PD-L1 expression level in the tumors. A 131 I-labeled anti-PD-L1 monoclonal antibody tracer, 131 I-PD-L1-Mab, was developed to study the target ability of non-invasive Cerenkov luminescence imaging in colorectal cancer xenograft mice.Method: Anti-PD-L1 monoclonal antibody labeled with 131 I( 131 I-PD-L1-Mab), and in vitro binding assays were used to evaluate the affinity of 131 I-PD-L1-Mab to PD-L1 and their binding level to different colorectal cancer cells, and compared with flow cytometry, western blot analysis, and immunofluorescence staining. The clinical application value of 131 I-PD-L1-Mab was evaluated through biodistribution and Cerenkov luminescence imaging, and different tumor-bearing models expressing PD-L1 were evaluated.Results: 131 I-PD-L1-Mab showed high affinity to PD-L1, and the equilibrium dissociation constant was 1.069×10 -9 M. The competitive inhibition assay further confirmed the specific binding ability of 131 I-PD-L1-Mab. In four different tumor-bearing models with different PD-L1 expression, the biodistribution and Cerenkov luminescence imaging showed that the RKO tumors demonstrated the highest uptake of the tracer 131 I-PD-L1-Mab, with a maximum uptake of 1.613 ± 0.738% ID/g at 120 h.Conclusions: There is a great potential for 131 I-PD-L1-Mab noninvasive Cerenkov luminescence imaging to assess the status of tumor PD-L1 expression and select patients for anti-PD-L1 targeted therapy.

Detection of Shortwave-Infrared Cerenkov Luminescence from Medical Isotopes

“…The success of preclinical VIS CLI has been widely established due to its relative ease and the wide availability of highly sensitive (single photon) cameras. [48][49][50][51] Initial experiments focused on ex vivo SWIR CLI to detect 18 F-FDG locally injected to a tumor on a xengofrafted mouse (see Supplemental Figure 2). However, the weak CL production of 18 F (22 times dimmer than 68 Ga) required the intratumoral administering of mCi's of radioisotope and lengthy acquisition times on the order of an hour for accurate signal detection.…”

A new light on prostate cancer

“…As the charged particle moves through the tissue, the atoms return to their ground state. The difference in energy between these states, is emitted as optical photons, also known as Cerenkov radiation (Figure 4) [42]. In other words, the Cerenkov radiation is produced by the medium as reaction to the charged particle, not by the charged particle itself; it is a so-called secondary emission [43].…”

“…CLI images can be acquired by detecting the Cerenkov light from PET tracers using sensitive optical cameras such as electron-multiplying charge-coupled device (emC-CD) cameras, one of these devices is shown in Figure 4 [42]. CLI and PET are directly correlated, as both techniques measure photons produced by positron-emitting radiopharmaceuticals; PET measures the annihilation photons, and CLI measures the Cerenkov photons.…”

“…F-FDG is sensitive enough to detect oral carcinoma, however, lacks specificity, which is needed for CLI imaging. Zirconium-89 ( 89 Zr) labelled anti-bodies [42,43] can be an option as well as the Cerenkov yield of 89 Zr is comparable to that of 18 F [44]. The first steps regarding the use of CLI in pulmonary and hepatic metastasectomy using 18 F-FDG and 68 Ga-DOTATOC respectively, have recently been undertaken [45].…”