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A Phase 0 Imaging Trial of [ 203 Pb]Pb-VMT-α-NET to Enable Dosimetry and Treatment Planning for Refractory or Relapsed Metastatic Neuroendocrine Tumors with [ 212 Pb]Pb-VMT-α-NET
Journal article   Peer reviewed

A Phase 0 Imaging Trial of [ 203 Pb]Pb-VMT-α-NET to Enable Dosimetry and Treatment Planning for Refractory or Relapsed Metastatic Neuroendocrine Tumors with [ 212 Pb]Pb-VMT-α-NET

Stephen A Graves, David L Bushnell, Michael K Schultz, Sanchay Jain, Kellie L Bodeker and Yusuf Menda
The Journal of nuclear medicine (1978)
02/05/2026
DOI: 10.2967/jnumed.125.270083
PMCID: PMC13041586
PMID: 41644295

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Abstract

Peptide receptor radionuclide therapy (PRRT) using α-particle emitters has potential to provide improved patient outcomes over those achieved with β-particle PRRT. A promising candidate radiopharmaceutical pair, PSC-PEG -TOC (VMT-α-NET) conjugated to Pb for SPECT/CT imaging or Pb for α-PRRT, is currently in early-phase clinical trials for patients with neuroendocrine tumors (NETs). Here, we present the imaging and dosimetry characteristics of this theranostic approach. A phase 0 imaging trial of [ Pb]Pb-VMT-α-NET was conducted between January and December of 2023. Ten participants with somatostatin receptor type 2 (SSTR2)-positive NETs underwent SPECT/CT and blood sampling at 1, 4, 24, and 48 h after intravenous infusion of approximately 185 MBq of [ Pb]Pb-VMT-α-NET. The diagnostic performance of [ Pb]Pb-VMT-α-NET was evaluated through lesion-by-lesion comparison against baseline SSTR2 PET/CT. A subset of lesions was further analyzed for signal-to-noise ratio to determine the optimal diagnostic imaging time point after [ Pb]Pb-VMT-α-NET administration. Patient-specific dosimetry of [ Pb]Pb-VMT-α-NET was derived from Pb imaging and performed assuming local α- and β-particle energy deposition in tumors and normal organs. Effects of daughter ion relocation were considered using a whole-body pharmacokinetic model on the basis of parameters published by the International Commission on Radiological Protection. Of the 162 total lesions identified on SSTR2 PET/CT scans, only 97 were detected on [ Pb]Pb-VMT-α-NET SPECT/CT. The highest signal-to-noise ratio for lesions occurred 4 h after [ Pb]Pb-VMT-α-NET administration. Sensitivity was 94% for lesions larger than 1 cm versus 35% for lesions no larger than 1 cm or nonmeasurable lesions. The effective dose associated with [ Pb]Pb-VMT-α-NET administration was 0.038 mSv/MBq (1.40 mSv/mCi). Estimated dosimetry for [ Pb]Pb-VMT-α-NET (mean ± SD, not adjusted for relative biologic effectiveness) based on [ Pb]Pb-VMT-α-NET SPECT/CT was 15 ± 4.7 mGy/MBq for the kidneys, 8.4 ± 4.1 mGy/MBq for the spleen, 2.5 ± 0.8 mGy/MBq for the liver, 0.324 ± 0.108 mGy/MBq for the blood, 0.270 ± 0.081 mGy/MBq for the whole body, and 29.6 ± 25.8 mGy/MBq for tumors. Renal absorbed dose projections for Pb were estimated to carry an overall standard uncertainty ( = 1) of 15.3%. [ Pb]Pb-VMT-α-NET appears to be a safe and effective SPECT/CT tracer for imaging NETs larger than 1 cm and for normal organ and tumor radiation dosimetry. The chemically matched / Pb theranostic pair offers the potential for a dosimetry-driven personalized treatment paradigm.
 α-PRRT [212Pb]Pb-VMT-α-NET radiopharmaceutical therapy [203Pb]Pb-VMT-α-NET neuroendocrine tumors

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