Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
Design, Preclinical Evaluation, and Clinical Translation of [68Ga]Ga/[177Lu]Lu-JH120061, a Novel Radiopharmaceutical Targeting CXCR4.
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Wang Guochang, Kang Tianrui, Peng Yumeng, Chen Shaohao, Chen Xingting, Lin Xiuting, Lai Yuxin, Zhan Jian, Yu Yaoming, Li Ruihong, Yu Haihua, Wang Eric, He Jinqiu, Ke Chunlin, Zang Jie, Xu Ning, Miao Weibing
Аннотация
PURPOSE: We designed and synthesized a novel compound targeting C-X-C motif chemokine receptor 4 (CXCR4), JH120061. Using clinically established Pentixafor and Pentixather as references, we evaluated the potential of [68Ga]Ga/[177Lu]Lu-JH120061 in a series of preclinical and clinical studies.
PATIENTS AND METHODS: Preclinical studies of [68Ga]Ga/[177Lu]Lu-JH120061 were conducted on CXCR4-expressing cell lines (HT1080-hCXCR4) and HT1080-hCXCR4 tumor-bearing mice. A head-to-head comparison of [68Ga]Ga-JH120061 with [68Ga]Ga-Pentixafor for PET/CT was conducted in patients with multiple myeloma (n = 5) and renal masses (n = 5). An expanded cohort of 53 patients with renal masses underwent [68Ga]Ga-JH120061 PET/CT to assess its performance in identifying renal malignancy.
RESULTS: Preclinical studies revealed that JH120061 demonstrated high binding affinity for CXCR4, promising cellular uptake and retention. In a clinical study, [68Ga]Ga-JH120061 PET/CT detected more malignant lesions than [68Ga]Ga-Pentixafor (94 vs. 81, P = 0.031) and showed significantly higher tumor uptake [maximum standardized uptake value (SUVmax) 22.3 ± 12.9 vs. 9.4 ± 6.5, P < 0.001, at 60 minutes]. Furthermore, [68Ga]Ga-JH120061 PET/CT exhibited excellent detectability for clear-cell renal cell carcinoma (ccRCC); its tumor uptake was significantly higher than that in non-ccRCC (SUVmax 28.9 ± 11.7 vs. 7.3 ± 2.4, P < 0.001).
CONCLUSIONS: This study demonstrated that JH120061 may have excellent affinity for CXCR4. Notably, [68Ga]Ga-JH120061 PET/CT demonstrated a remarkable capability for detecting ccRCC. Future studies should further explore the potential of [68Ga]Ga/[177Lu]Lu-JH120061 in precision theranostics of CXCR4-positive tumors.
PATIENTS AND METHODS: Preclinical studies of [68Ga]Ga/[177Lu]Lu-JH120061 were conducted on CXCR4-expressing cell lines (HT1080-hCXCR4) and HT1080-hCXCR4 tumor-bearing mice. A head-to-head comparison of [68Ga]Ga-JH120061 with [68Ga]Ga-Pentixafor for PET/CT was conducted in patients with multiple myeloma (n = 5) and renal masses (n = 5). An expanded cohort of 53 patients with renal masses underwent [68Ga]Ga-JH120061 PET/CT to assess its performance in identifying renal malignancy.
RESULTS: Preclinical studies revealed that JH120061 demonstrated high binding affinity for CXCR4, promising cellular uptake and retention. In a clinical study, [68Ga]Ga-JH120061 PET/CT detected more malignant lesions than [68Ga]Ga-Pentixafor (94 vs. 81, P = 0.031) and showed significantly higher tumor uptake [maximum standardized uptake value (SUVmax) 22.3 ± 12.9 vs. 9.4 ± 6.5, P < 0.001, at 60 minutes]. Furthermore, [68Ga]Ga-JH120061 PET/CT exhibited excellent detectability for clear-cell renal cell carcinoma (ccRCC); its tumor uptake was significantly higher than that in non-ccRCC (SUVmax 28.9 ± 11.7 vs. 7.3 ± 2.4, P < 0.001).
CONCLUSIONS: This study demonstrated that JH120061 may have excellent affinity for CXCR4. Notably, [68Ga]Ga-JH120061 PET/CT demonstrated a remarkable capability for detecting ccRCC. Future studies should further explore the potential of [68Ga]Ga/[177Lu]Lu-JH120061 in precision theranostics of CXCR4-positive tumors.