Research ArticleFEATURED CLINICAL INVESTIGATION ARTICLE
Open Access

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

Changsong Qi, Rui Guo, Yan Chen, Chenzhen Li, Chang Liu, Miao Zhang, Cheng Zhang, Xiaotian Zhang, Xingguo Hou, Bo Chen, Bing Jia, Zhi Yang, Lin Shen and Hua Zhu
Journal of Nuclear Medicine June 2024, 65 (6) 856-863; DOI: https://doi.org/10.2967/jnumed.123.267110

Article Figures & Data

Figures

  • Figure
  • FIGURE 1.
    FIGURE 1.

    68Ga-NC-BCH PET images of mice bearing AGSCLDN18.2 and AGS tumors. Block = incubation with 1 mg of TST001 in mice bearing AGSCLDN18.2 xenografted 24 h in advance.

  • FIGURE 2.
    FIGURE 2.

    (A) Dynamic changes in SUVmean of selected organs at 0–42 min (n = 5). (B) Rank ordering of 68Ga-NC-BCH uptake in different organs indicated by SUVmean at 42 min (n = 5). (C) Pilot translational study on dynamic total-body PET/CT imaging of 68Ga-NC-BCH illustrating time distribution of radiotracers within tumors to optimize imaging window.

  • FIGURE 3.
    FIGURE 3.

    (A) Tumor uptake of 68Ga-NC-BCH in different metastatic lesions. (B) Comparison of tumor-to-liver ratio between 68Ga-NC-BCH and 18F-FDG. (C) Comparison of tumor-to-nontumor ratio between 68Ga-NC-BCH and 18F-FDG in different metastatic lesions. *P < 0.05. **P < 0.01. ns = not statistically significant.

  • FIGURE 4.
    FIGURE 4.

    (A) Box plot of 68Ga-NC-BCH SUVmax and 18F-FDG SUVmax for all lesions in 11 patients with CLDN18.2 +++ and CLDN18.2 ++ by immunohistochemistry staining. (B) Box plot of 68Ga-NC-BCH for all lesions in 11 patients with CLDN18.2-targeted therapy and without CLDN18.2-targeted therapy. Data are mean ± SD.***P < 0.001. ns = not statistically significant.

  • FIGURE 5.
    FIGURE 5.

    (A) Muscle metastases in right lower abdominal wall with mild elevated uptake. (B–D) Multiple lymph node metastasis showing CLDN18.2 expression degree from low (B) to high (D) (left) and imaging of 68Ga-NC-BCH of patient (right).

  • FIGURE 6.
    FIGURE 6.

    (A) Patient 9 was woman with advanced gastric cancer whose CLDN18.2 expression level was 40%, 2+. Left pleural metastatic nodule (blue arrow) and thickened peritoneum (white arrow) did not show obvious uptake on 18F-FDG PET/CT, whereas 68Ga-NC-BCH PET/CT showed high uptake (SUVmax, 3.1 [red arrow] and 5.7 [green arrow]). (B) Patient 4 was man with colon cancer whose CLDN18.2 expression level was 40%, 3+. On 18F-FDG PET/CT, abdominal metastatic lymph node (white arrow) showed mild uptake, whereas same lymph nodes on 68Ga-NC-BCH PET/CT (blue arrow) showed high uptake (SUVmax, 1.4 vs. 5.6).

  • FIGURE 7.
    FIGURE 7.

    Graphs of survival time. (Top) Green depicts group above—and dark yellow, group below—mean CLDN18.2 expression of 40%. (Middle) Green depicts clinical stage of 4, and dark yellow depicts clinical stage < 4. (Bottom) Green depicts group below—and dark yellow, group above—mean SUVmax of 2.5. HR = hazard ratio.

Tables

  • TABLE 1.

    Patient Characteristics

    Patient no.Age (y)SexWeight (kg)Clinical stageCLDN18.2-targeted therapy before PET
    160M61cT4aN+M1No
    230F54cT3N3M1No
    368F58cT4bN2M1No
    440M69cT4N2M1No
    551F52T3N2M0No
    637M59pT2N1MxYes
    741M60cT4bNxM1Yes
    831F41pT4aN3aNo
    928F47T4aN3aM1Yes
    1031F43pT3N1M1Yes
    1137F55cT4aN2M0Yes
  • TABLE 2.

    Comparison of SUVmax of 68Ga-NC-BCH with 18F-FDG in Metastases

    Patient no.Tumor typeCLDN18.2 expressionTime between prior anti-CLDN18.2 therapy and experiment (mo)Prior therapy linesGastrectomyMetastatic lesion68Ga-NC-BCH18F-FDG
    1Gastric cancer90%, 3+—3YesPeritoneum54.7
    Bone9.719.8
    Liver7.618.9
    Lymph node7.110.9
    2Gastric cancer80%, 3+—3NoLymph nodeNegative8.9
    3Gastric cancer40%, 2+—3NoPeritoneum2.52
    Lymph node18.64.7
    4Colorectal cancer40%, 3+—3NoPeritoneum3.12.1
    Lymph node5.11.7
    5Gastric cancer90%, 3+—3No—NegativeNegative
    6Gastric cancer50%, 2+10.53YesAnastomosis4.27.7
    Lymph node2.29.1
    Peritoneum2.110.1
    Subcutaneous tissue1.55.7
    7Gastric cancer90%, 3+33NoLymph node6.5Negative
    Abdominal wall2.31.7
    Peritoneum4.11.7
    8Gastric cancer90%, 3+—3NoPeritoneum4.2Negative
    Bone2.38
    Ovary2.01.8
    9Gastric cancer40%, 2+5.53YesPeritoneum4.91
    Subcutaneous tissue6.62.1
    Pleura3.2Negative
    10Gastric cancer90%, 3+152YesPeritoneum4.71.8
    Lymph node10.11.6
    Muscle2.0Negative
    11Gastric cancer60%, 2+6.53NoPeritoneum33
    Lymph node2.11.9

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