Preliminary application of 125I–nivolumab to detect PD-1 expression in colon cancer via SPECT

Li, Danni; Wang, Cheng; Zhang, Dakuan; Ye, Peng; Ren, Shengnan; Li, Xiao; Zuo, Chao

doi:10.1007/s10967-018-6124-6

Cited by 8 publications

(8 citation statements)

References 25 publications

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“…In our previous work, we evaluated the pharmacokinetic properties of I-125 labeled nivolumab using the nude mouse xenograft model of colorectal carcinoma. Since only the B and NK cells were used, we could prove PD-1 targeting partially ( Li et al, 2018 ). In this study, the tumor growth and angiogenesis of in situ tumor models were almost achieved in the humanized mouse cancer model, and therefore, the results obtained for systemic uptake of antibodies-based tracers were more convincing.…”

Section: Discussionmentioning

confidence: 99%

“…Splenocytes were isolated from the spleens obtained from humanized PD-1 over-expressing mice following standard protocol. Referring to our previous labeling protocol ( Li et al, 2018 ), 125 I labeled Nivolumab and Nivolumab-DTPA, respectively. To perform co-culture, 125 I-Nivolumab and 125 I-Nivolumab-DTPA (0.37 MBq/µg) were added to the freshly isolated splenocytes (1×10 6 cells) grown in 6-well plates, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Nivolumab-DTPA-Based PD-1 Imaging Reveals Structural and Pathological Changes in Colorectal Carcinoma

Yang

et al. 2022

Front. Bioeng. Biotechnol.

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Programmed cell death protein 1 (PD-1) expression is considered a prognostic marker of tumor response to the immuno-blocking therapy. In this study, nivolumab was conjugated with diethylenetriamine pentaacetate (DTPA) via condensation reaction between amidogen and p-SCN-Bn-DTPA, which provided labeling sites for 99mTc4+ or Gd3+ ions. SPECT and magnetic resonance T1 weighted imaging (T1WI) analyses were performed on mouse models of colorectal carcinoma expressing humanized PD-1 antigen. Furthermore, PD-1 expression in intestinal tracks was assessed by immunohistochemistry, and then compared with the imageological findings. Nivolumab-DTPA was synthesized with varying molar ratios and was labeled with Gd or 99mTc with a chemical purity of 96.28 ± 1.16% and good stability. In SPECT images, lesions with high 99mTc-DTPA-nivolumab uptake and relatively clear background were shown at 6 h. Thereafter, the suspected intestinal thickening in Gd-free T1WI was observed at 2 h after the addition of Gd-DTPA-nivolumab. Notably, the results of both SPECT and T1WI analyses were consistent with the postmortem examination and immunohistochemistry results (for linear correlation with target to non-target ratios, R2 = 0.8038, p < 0.05). In conclusion, nivolumab-DTPA could act as a probe precursor for identifying PD-1-positive lesions, not only through integrating the advantages of immunohistochemistry and molecular imaging but also by providing a noninvasive method for monitoring systemic changes.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Nivolumab-DTPA-Based PD-1 Imaging Reveals Structural and Pathological Changes in Colorectal Carcinoma

Yang

et al. 2022

Front. Bioeng. Biotechnol.

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“…In terms of PD-1/PD-L1 molecular imaging, the targeting ability and metabolic pathway of the probes play a key role. Objective issues such as poor penetration of intact antibodies in solid tumor tissue, low stability, restricted routes of drug delivery and difficulty to control pharmacokinetics limit their use in clinics [10].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of 68Ga-labeled TPP-1: A Targeted PD-L1 Probe for PET Imaging of Colorectal Cancer

Wang¹,

Li²,

Li³

et al. 2021

GMR

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Although PD-1/PD-L1 immuno-blocking therapy (IBT) has improved the prognosis of patients with gastrointestinal tumors to some extent, not all patients respond to IBT. Recent studies have shown that PD-L1 antigen expression in tumors is prognostic marker of response to PD-1/PD-L1 IBT. Here, 68 Ga-TPP-1 was developed for specific and non-invasive imaging of PD-L1 expression in mouse models of colorectal cancer. Positron emission tomography (PET) and immunohistochemistry (IHC) results confirmed the highly specific targeting of 68 Ga-TPP-1 in PD-L1 expressing colorectal cancer mice.

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“…125 Ilabeled nivolumab, another U.S. Food and Drug Administration-approved antihuman PD-1 antibody, was used to image PD-1 expression via single-photon emission computed tomography in a colon cancer xenograft model. 17 However, PD-1-targeted imaging does not directly visualize the primary tumor; rather, it visualizes the trafficking of PD-1-expressing immune cells. In contrast, PD-L1-targeted imaging visualizes tumor cells and other stromal cells.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Although 89 Zr-labeled antibodies in general yield an excellent tumor-to-background ratio due to clearance of radiotracers from normal organs at delayed times (72–168 h post-injection), the long half-life of 89 Zr raises concern over increased radiation exposure and potential radiotoxicity. 125 I-labeled nivolumab, another U.S. Food and Drug Administration-approved antihuman PD-1 antibody, was used to image PD-1 expression via single-photon emission computed tomography in a colon cancer xenograft model . However, PD-1-targeted imaging does not directly visualize the primary tumor; rather, it visualizes the trafficking of PD-1-expressing immune cells.…”

Section: Introductionmentioning

confidence: 99%

Concurrent Injection of Unlabeled Antibodies Allows Positron Emission Tomography Imaging of Programmed Cell Death Ligand 1 Expression in an Orthotopic Pancreatic Tumor Model

Zhao¹,

Wen²,

Li³

et al. 2020

ACS Omega

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Among the treatment options for pancreatic ductal adenocarcinoma (PDAC) are antibodies against the programmed cell death receptor 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway. Positron emission tomography (PET) has been successfully used to assess PD-1/PD-L1 signaling in subcutaneous tumor models, but orthotopic tumor models are increasingly being recognized as a better option to accurately recapitulate human disease. However, when PET radiotracers have high uptake in the liver and spleen, it can obscure signals from the adjacent pancreas, making visualization of the response in orthotopic pancreatic tumors technically challenging. In this study, we first investigated the impact of radioisotope chelators on the biodistribution of 64 Cu-labeled anti-PD-1 and anti-PD-L1 antibodies and compared the distribution profiles of anti-PD-1 and anti-PD-L1 antibodies. We then tested the hypothesis that co-injection of unlabeled antibodies reduces uptake of 64 Cu-labeled anti-PD-L1 antibodies in the spleen and thereby permits accurate delineation of orthotopic pancreatic tumors in mice. Procedures: We established subcutaneous and orthotopic mouse models of PDAC using KRAS* murine pancreatic cancer cells with a doxycycline-inducible mutation of KRAS G12D . We then (1) compared the biodistribution of 64 Cu-labeled anti-PD-1 with 2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA) and 2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) used as the chelators in the orthotopic model; (2) compared the biodistribution of [ 64 Cu]Cu-NOTA-anti-PD-1 and [ 64 Cu]Cu-NOTA-anti-PD-L1 in the orthotopic model; and (3) imaged subcutaneous and orthotopic KRAS* tumors with [ 64 Cu]Cu-NOTA-anti-PD-L1 with and without co-injection of unlabeled anti-PD-L1 as the blocking agent. Results: [ 64 Cu]Cu-NOTA-anti-PD-L1 was a promising imaging probe. By co-injection of an excess of unlabeled anti-PD-L1, background signals of [ 64 Cu]Cu-NOTA-anti-PD-L1 from the spleen were significantly reduced, leading to a clear delineation of orthotopic pancreatic tumors. Conclusions: Co-injection with unlabeled anti-PD-L1 is a useful method for PET imaging of PD-L1 expression in orthotopic pancreatic cancer models.

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Preliminary application of 125I–nivolumab to detect PD-1 expression in colon cancer via SPECT

Cited by 8 publications

References 25 publications

Nivolumab-DTPA-Based PD-1 Imaging Reveals Structural and Pathological Changes in Colorectal Carcinoma

Nivolumab-DTPA-Based PD-1 Imaging Reveals Structural and Pathological Changes in Colorectal Carcinoma

Evaluation of 68Ga-labeled TPP-1: A Targeted PD-L1 Probe for PET Imaging of Colorectal Cancer

Concurrent Injection of Unlabeled Antibodies Allows Positron Emission Tomography Imaging of Programmed Cell Death Ligand 1 Expression in an Orthotopic Pancreatic Tumor Model

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