Optimal imaging timepoint for diagnostic performance of 203Pb-VMT-α-NET SPECT/CT in neuroendocrine tumors

Introduction: Patients with metastatic neuroendocrine tumors who have progressed or relapsed following treatment with [177Lu] -DOTATATE currently have very limited treatment options to delay progression and prolong life. Alpha-emitting SSTR ligand therapy appears promising as a potential treatment option in this clinical setting. A reliable imaging method for better assessment of tumor distribution and dosimetry along with normal organ dosimetry is crucial to implement optimal development of alpha particle therapy for this purpose. This abstract focuses on determination of preferred imaging timepoint(s) for diagnostic/dosimetric performance of [²⁰³Pb]-VMT-α-NET in neuroendocrine tumors.

Methods: A phase 0 imaging trial of [²⁰³Pb] VMT-α-NET (also referred to as [²⁰³Pb] PSC-PEG2-TOC) was conducted between January and December of 2023 (NCT05111509). Inclusion criteria included established NETs (grade 1 or 2); at least one primary metastatic lesion that was positive on SSTR2 PET imaging within 12 months of consent and measurable soft tissue tumor size of ≥ 2.0 cm in any dimension on computed tomography (CT) or magnetic resonance (MR) imaging; progressed at any time on or following therapy with [¹⁷⁷Lu] Lu-DOTATATE; age ≥ 18 years. SPECT/CT imaging was performed at 1h, 4h, 24h and 48h after intravenous infusion of ~185 MBq [²⁰³Pb] VMT-α-NET. Imaging was performed using a 20% energy window about the 279 keV photopeak with 10% upper and lower scatter windows. Images were reconstructed and analyzed in MIM Software using 3DOSEM, 8 iterations, 12 subsets, 5 mm Gaussian filter, with collimator detector response modeling included. For each lesion identified, an anatomic contour was created using the CT scan, followed by morphologic expansion of 10 mm to create a functional contour (thereby encompassing partial volume effects). An additional hollow-shell "ring" contour was created beyond the functional contour to determine local background concentration and estimate noise quality. A 5 cm sphere was placed in normal liver to evaluate liver uptake. Tumor uptake, tumor-to-liver ratio, estimated signal-to-noise ratio (eSNR), and estimated contrast-to-noise ratio (eCNR) were calculated to assess the optimal imaging timepoint.

Results: Forty-eight lesions were analysed in nine patients. Tumor uptake (total imaging counts in functional contour) was rapid, reaching a maximum at ~4 hours p.i., and falling thereafter (98% of max at 1h; 31% of max at 24h; 16% of max at 48h). Tumor-to-liver concentration ratio increased steadily over time, with values of 15.5, 17.5, 32.9, and 45.9 at 1h, 4h, 24h, and 48h, respectively. Lesion detectability, as measured by eSNR and eCNR, reached a maximum at 4 hours, average eSNR values of 224, 236, 142, and 80, eCNR values of 151, 168, 107, and 54, at 1h, 4h, 24h, and 48h, respectively.

Conclusions: Imaging with [²⁰³Pb] VMT-α-NET at 4 hours post-injection has the best overall diagnostic performance , followed closely by imaging at 1 hour. Although, the tumor-to-liver ratio continues to increase at later timepoints (24 h, 48 h), the noise penalty of lower count-rates reduces the SNR and CNR, and thereby, lesion detectability beyond the first day. In patients with low-contrast liver lesions, and a negative 4-hour ²⁰³Pb imaging study, repeat imaging at 24 hours post-injection may provide additional diagnostic information.