CD70-targeted platform for diagnosing and treating multiple myeloma.

CD70 was overexpressed in 66.7% of patient multiple myeloma samples and confirmed in RPMI-8226 xenografts.

• CD70 positivity rate in patient MM samples was 66.7%
• CD70 expression was also confirmed in RPMI-8226 xenograft tumor models used for subsequent experiments
• This confirmed CD70 as a viable theranostic target in MM

[89Zr]Zr-DFO-ABDB6 demonstrated high tumor uptake and favorable tumor-to-muscle ratios in an MM model.

• Tumor uptake was 7.81±0.79% ID/g at 72 hours post-injection
• Tumor-to-muscle ratios reached up to 10.63±5.71
• The tracer was evaluated using immuno-positron emission tomography (immuno-PET)
• Pharmacokinetics and biodistribution were evaluated in NCG and nude mice

[177Lu]Lu-DOTA-ABDB6 at therapeutic doses of 40–80 µCi suppressed tumor growth and significantly extended median survival in MM tumor-bearing mice.

• Median survival was extended to 61–69 days in treated groups versus 35–36 days in control groups
• Tumor volume measurement and survival analysis were used to assess therapeutic efficacy
• Experiments were conducted in RPMI-8226 tumor-bearing mice
• The dose range of 40–80 µCi was identified as both safe and effective

Higher doses of [177Lu]Lu-DOTA-ABDB6 (300–600 µCi) caused transient hematotoxicity and organ stress that resolved by 28 days.

• Hematotoxicity and organ stress were observed at doses of 300–600 µCi
• These adverse effects were transient and resolved by day 28
• Toxicity evaluation was performed in NCG and nude mice
• This finding established a safety boundary distinguishing low therapeutic doses from higher toxic doses

Tumor relapse occurred after single-dose [177Lu]Lu-DOTA-ABDB6 treatment, indicating the need for regimen optimization.

• Tumor relapse was observed following single-dose treatment at the therapeutic dose range
• The authors concluded this indicates 'the need for regimen optimization'
• Future studies were recommended to explore repeated dosing or alpha-emitters such as 225Ac to improve durability

The nanobody derivative ABDB6 was successfully conjugated to chelators DFO and DOTA and radiolabeled with 89Zr and 177Lu, respectively, to form a matched theranostic pair.

• ABDB6 is described as a 'nanobody derivative' targeting CD70
• DFO conjugation enabled radiolabeling with 89Zr for PET imaging
• DOTA conjugation enabled radiolabeling with 177Lu for targeted radionuclide therapy
• The pair was designed to combine imaging and radiotherapy (theranostics) for MM management