{
  "abstract": "Background CD70, overexpressed in multiple myeloma (MM), is a promising target for theranostics. This study developed a CD70-targeted theranostic pair: the immuno-positron emission tomography tracer [ 89Zr]Zr-DFO-ABDB6 and the therapeutic agent [177Lu]Lu-DOTA-ABDB6, aiming to combine imaging and radiotherapy for MM.Methods CD70 expression was confirmed in patients with MM samples (positivity rate, 66.7%) and RPMI-8226 xenografts. The nanobody derivative ABDB6 was conjugated to DFO or DOTA and radiolabeled with 89Zr or 177Lu. Pharmacokinetics, biodistribution, and toxicity were evaluated in NCG and nude mice. Therapeutic efficacy was assessed in RPMI-8226 tumor-bearing mice via tumor volume measurement and survival analysis.Results [ 89Zr]Zr-DFO-ABDB6 showed high tumor uptake (7.81±0.79% ID/g at 72 hours) and tumor-to-muscle ratios up to 10.63±5.71 in an MM model. [177Lu]Lu-DOTA-ABDB6 treatment at a therapeutic dose of 40–80 µCi suppressed tumor growth and extended median survival to 61–69 days (vs 35–36 days in the control group). [177Lu]Lu-DOTA-ABDB6 treatment at higher doses (300–600 µCi) caused transient hematotoxicity and organ stress, which resolved by 28 days. Tumor relapse occurred after single-dose treatment, indicating the need for regimen optimization.Conclusions The CD70-targeted theranostic pair allows precise imaging and effective radiotherapy in MM models. Low-dose [ 177Lu]Lu-DOTA-ABDB6 treatment (40–80 µCi) is safe and effective, supporting clinical translation. Future studies should explore repeated dosing or the use of alpha-emitters (eg, 225Ac) to improve durability. [89Zr]Zr-DFO-ABDB6/[177Lu]Lu-DOTA-ABDB6 theranostic pair provides a novel management strategy for CD70-positive MMs.",
  "authors": [
    {
      "affiliations": [
        "Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"
      ],
      "name": "Jun Li"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"
      ],
      "name": "Haoyi Yan"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"
      ],
      "name": "Xiaoyan Wang"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "You Zhang"
    },
    {
      "affiliations": [
        "Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"
      ],
      "name": "Ping Chen"
    },
    {
      "affiliations": [
        "Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"
      ],
      "name": "Jia Feng"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"
      ],
      "name": "Rui Zhang"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"
      ],
      "name": "Zhan Li"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"
      ],
      "name": "Zixuan Huang"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"
      ],
      "name": "Chuanmian Xu"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"
      ],
      "name": "Ning Ma"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"
      ],
      "name": "Xiaohua Lin"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China",
        "Department of Cell Therapy, The Seventh Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China"
      ],
      "name": "Minyi Zhao"
    },
    {
      "affiliations": [
        "Institute of Biomedical Engineering, Shenzhen Bay Lab, Shenzhen, Guangdong, China"
      ],
      "name": "Wenjing Zhu"
    },
    {
      "affiliations": [
        "Institute of Biomedical Engineering, Shenzhen Bay Lab, Shenzhen, Guangdong, China"
      ],
      "name": "Qiyu Peng"
    },
    {
      "affiliations": [
        "Institute of Biomedical Engineering, Shenzhen Bay Lab, Shenzhen, Guangdong, China"
      ],
      "name": "Siwei Xie"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Weijun Wei"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China"
      ],
      "name": "Mengjie Dong"
    }
  ],
  "title": "CD70-targeted platform for diagnosing and treating multiple myeloma",
  "uid": "d6cdd4a6-2097-5599-9bd5-e8c80d39665a"
}