Journal article
[ 203/212 Pb]Pb-VMT-α-NET as a novel theranostic agent for targeted alpha radiotherapy-first clinical experience
European journal of nuclear medicine and molecular imaging, Vol.52(11), pp.4171-4183
09/2025
DOI: 10.1007/s00259-025-07269-0
PMCID: PMC12397198
PMID: 40202686
Abstract
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 [
Pb]Pb-VMT-α-NET regarding imaging, biokinetics, tolerability and response.
12 patients (9 m/3 w; mean age 71, range 60-84) with progressive metastatic GEP-NET grade 1-3 received diagnostic imaging with [
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 [
Pb]Pb-VMT-α-NET therapy (1.2 MBq/kg bw) after exhaustion of all current therapies (including [
Lu]Lu- & [
Ac]Ac-DOTATATE), and post-treatment imaging with [
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 [
Ga]Ga-DOTATATE PET scans before and 3 months after therapy.
No high-grade adverse effects were observed in all patients evaluated with [
Pb]Pb-VMT-α-NET. All patients showed an initial high, but lesion-dependent heterogeneous intratumoral accumulation, comparable to [
Ga]Ga-DOTATATE PET. Treatment with [
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.
Imaging with [
Pb]Pb-VMT-α-NET followed by a single dose of [
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.
Details
- Title: Subtitle
- [ 203/212 Pb]Pb-VMT-α-NET as a novel theranostic agent for targeted alpha radiotherapy-first clinical experience
- Creators
- Enrico Michler - University Hospital Carl Gustav CarusDavid Kästner - University Hospital Carl Gustav CarusMarc Pretze - University Hospital Carl Gustav CarusHolger Hartmann - University Hospital Carl Gustav CarusRobert Freudenberg - University Hospital Carl Gustav CarusMichael K Schultz - Perspective Therapeutics Inc., Coralville, IA, USARalph A Bundschuh - University Hospital Carl Gustav CarusJörg Kotzerke - University Hospital Carl Gustav CarusClaudia Brogsitter - University Hospital Carl Gustav Carus
- Resource Type
- Journal article
- Publication Details
- European journal of nuclear medicine and molecular imaging, Vol.52(11), pp.4171-4183
- DOI
- 10.1007/s00259-025-07269-0
- PMID
- 40202686
- PMCID
- PMC12397198
- NLM abbreviation
- Eur J Nucl Med Mol Imaging
- ISSN
- 1619-7070
- eISSN
- 1619-7089
- Publisher
- SPRINGER
- Grant note
- Universittsklinikum Carl Gustav Carus Dresden an der Technischen Universitt Dresden (8944)
The authors would like to thank Perspective Therapeutics, Inc. for supplying the VMT-alpha-NET precursor, 203Pb radionuclides and 212Pb isotope generators for the production of the radiopharmaceuticals used in this work
- Language
- English
- Electronic publication date
- 04/09/2025
- Date published
- 09/2025
- Academic Unit
- Radiology; Radiation Oncology
- Record Identifier
- 9984808285202771
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