Abstract
[212Pb]Pb-VMT-a-NET dosimetry in patients with advanced SSTR2-positive tumors in the VMT-a-NET-T101 trial
The Journal of nuclear medicine (1978), Vol.66(Suppl 1), p.1
06/01/2025
Abstract
Introduction: [212Pb]Pb-VMT-a-NET is a novel alpha-emitting radiopharmaceutical therapy (RPT) developed for the treatment of somatostatin receptor subtype 2 expressing (SSTR2) tumors. VMT-a-NET-T101 (NCT05636618) is a multi-center, phase I/IIa, first-in-human trial of [212Pb]Pb-VMT-a-NET in PRRT-na ve patients with unresectable or metastatic SSTR2+ neuroendocrine tumors. As part of this investigation, a subset of patients were enrolled in a dosimetry sub-study utilizing pre-treatment SPECT imaging of [203Pb]Pb-VMT-a-NET. Here we present preliminary dosimetry analysis for [212Pb]Pb-VMT-a-NET based on theranostic imaging studies of [203Pb]Pb-VMT-a-NET. Methods: Participants of the VMT-a-NET-T101 trial receive four administrations of [212Pb]Pb-VMT-a-NET at 8-week intervals in cohorts of escalating dose with the objective to evaluate the tolerability of [212Pb]Pb-VMT-a-NET, characterize blood and urine pharmacokinetics, and determine the recommended phase 2 dose. Patient eligibility for VMT-a-NET-T101 was based on DOTATATE PET imaging. Prior to receiving therapy, patients included in the dosimetry sub-study received 6 mCi (222 MBq) of [203Pb]Pb-VMT-a-NET with concurrent amino acid infusion followed by quantitative SPECT/CT imaging at 1, 4, and 24 hours. 203Pb SPECT images were reconstructed using the 279 keV photopeak projection data, using CT-based attenuation correction and window-based scatter correction methods. Regions of interest were delineated for the kidneys, liver, spleen, and tumors based on anatomic and functional imaging. Partial-volume corrected time-activity curves were generated for [212Pb]Pb-VMT-a-NET, accounting for the differences in physical decay between 203Pb (51.9 hours) and 212Pb (10.6 hours). Bone marrow dosimetry was estimated based on blood PK measurements of [203Pb]Pb-VMT-a-NET. Dosimetry calculations were performed based on the MIRD methodology using OLINDA 2.2.3. Results: As of the data cutoff (Oct 31, 2024), six patients enrolled in the trial had completed the dosimetry sub-study. The time interval between SPECT imaging of [203Pb]Pb-VMT-a-NET and administration of [212Pb]Pb-VMT-a-NET was 9 5 days. Predicted time activity curves for [212Pb]Pb-VMT-a-NET showed that the tumor-to-kidney ratio of uptake (%IA/L) peaked at 2.8 1.3 at 4 hours and remained robust through 24 hours post administration. Tumor absorbed dose (n = 16 tumors) showed greater variability than organ absorbed dose among patients, with tumor doses ranging to as high as 14.1 Gy (RBE=1) per 5 mCi (185 MBq) of [212Pb]Pb-VMT-a-NET. Additional imaging and dosimetry studies in VMT-a-NET-T101 are ongoing. Conclusions: Theranostic investigations with [203Pb]Pb-VMT-a-NET provide an accurate and reliable means to predict dosimetry for alpha-particle RPT with [212Pb]Pb-VMT-a-NET. Dosimetric analysis of VMT-a-NET-T101 multi-timepoint imaging with [203Pb]Pb-VMT-a-NET in the screening stage of the trial demonstrates that [212Pb]Pb-VMT-a-NET has a favorable ratio of absorbed dose in tumors relative to kidneys. Additional comprehensive dosimetry analyses for sub-study patients will be presented at the congress.
Details
- Title: Subtitle
- [212Pb]Pb-VMT-a-NET dosimetry in patients with advanced SSTR2-positive tumors in the VMT-a-NET-T101 trial
- Creators
- Stephen GravesThorvardur HalfdanarsonRichard WahlLowell AnthonyLilja SolnesSam MehrIan MarshLucia BarattoStephen KeefeMarkus PuhlmannVikas Prasad - Washington University in St. Louis
- Resource Type
- Abstract
- Publication Details
- The Journal of nuclear medicine (1978), Vol.66(Suppl 1), p.1
- ISSN
- 0161-5505
- eISSN
- 1535-5667
- Publisher
- Society of Nuclear Medicine
- Language
- English
- Date published
- 06/01/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Radiation Oncology
- Record Identifier
- 9984927079602771
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