[203/212Pb]Pb-VMT-α-NET as a novel theranostic agent for targeted alpha radiotherapy—first clinical experience

Abstract

Abstract Purpose 203/212 Pb is a promising theranostic isotope pair for targeted alpha therapy (TAT) of neuroendocrine tumors (NET). VMT-α-NET is a novel SSTR2 targeting peptide that can be labeled with both isotopes. The aim of this work was to perform first clinical investigations of [ 203/212 Pb]Pb-VMT-α-NET regarding imaging, biokinetics, tolerability and response. Methods 12 patients (9 m/3 w; mean age 71, range 60–84) with progressive metastatic GEP-NET grade 1–3 received diagnostic imaging with [ 203 Pb]Pb-VMT-α-NET (4.9 MBq/kg bw) up to 24 h p.i. (whole body & SPECT/CT) and, if eligible, a single dose of [ 212 Pb]Pb-VMT-α-NET therapy (1.2 MBq/kg bw) after exhaustion of all current therapies (including [ 177 Lu]Lu- & [ 225 Ac]Ac-DOTATATE), and post-treatment imaging with [ 212 Pb]Pb-VMT-α-NET up to 24 h p.i. (whole body & SPECT/CT). Clinical and laboratory parameters were monitored. A visual and quantitative comparison was made with [ 68 Ga]Ga-DOTATATE PET scans before and 3 months after therapy. Results No high-grade adverse effects were observed in all patients evaluated with [ 203 Pb]Pb-VMT-α-NET. All patients showed an initial high, but lesion-dependent heterogeneous intratumoral accumulation, comparable to [ 68 Ga]Ga-DOTATATE PET. Treatment with [ 212 Pb]Pb-VMT-α-NET was also well tolerated by all patients without high-grade or serious adverse side effects. Post-therapeutic PET scans and tumor marker controls showed stable findings in all patients up to 3 months after treatment. Conclusion Imaging with [ 203 Pb]Pb-VMT-α-NET followed by a single dose of [ 212 Pb]Pb-VMT-α-NET appears to be well tolerated with promising efficacy, even in a heterogenous and heavily pretreated patient population. Further studies are warranted to examine tolerability and efficacy over multiple treatment cycles in larger patient populations.

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