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This study developed a CD70-targeted theranostic pair: the immuno-positron emission tomography tracer [\n                      <jats:sup>89<\/jats:sup>\n                      Zr]Zr-DFO-ABDB6 and the therapeutic agent [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-DOTA-ABDB6, aiming to combine imaging and radiotherapy for MM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:sup>89<\/jats:sup>\n                      Zr or\n                      <jats:sup>177<\/jats:sup>\n                      Lu. 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>89<\/jats:sup>\n                      Zr]Zr-DFO-ABDB6 showed high tumor uptake (7.81\u00b10.79%\u2009ID\/g at 72 hours) and tumor-to-muscle ratios up to 10.63\u00b15.71 in an MM model. [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-DOTA-ABDB6 treatment at a therapeutic dose of 40\u201380\u2009\u00b5Ci suppressed tumor growth and extended median survival to 61\u201369 days (vs 35\u201336 days in the control group). [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-DOTA-ABDB6 treatment at higher doses (300\u2013600\u2009\u00b5Ci) caused transient hematotoxicity and organ stress, which resolved by 28 days. Tumor relapse occurred after single-dose treatment, indicating the need for regimen optimization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The CD70-targeted theranostic pair allows precise imaging and effective radiotherapy in MM models. Low-dose [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-DOTA-ABDB6 treatment (40\u201380 \u00b5Ci) is safe and effective, supporting clinical translation. Future studies should explore repeated dosing or the use of alpha-emitters (eg,\n                      <jats:sup>225<\/jats:sup>\n                      Ac) to improve durability. [\n                      <jats:sup>89<\/jats:sup>\n                      Zr]Zr-DFO-ABDB6\/[\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-DOTA-ABDB6 theranostic pair provides a novel management strategy for CD70-positive MMs.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014058","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:55:20Z","timestamp":1780919720000},"page":"e014058","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["CD70-targeted platform for diagnosing and treating multiple myeloma"],"prefix":"10.1136","volume":"14","author":[{"given":"Jun","family":"Li","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 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