Dose Optimization and Diagnostic Performance in Prostate Cancer (SPARROW [Staging Prostate Cancer With Advanced RM2 Radiotracer Oncologic Workup])

Phase 2 Dose Optimization Period During the Phase 2 period, participants will receive 5 (±1) mCi (148 to 222 MBq) of \[68Ga\]-LNTH-2401 for PET/CT imaging with the primary objectives of determining the optimal administered activity, imaging parameters and tissue dosimetry. Up to 12 participants with GRPR-positive lesion(s) will undergo serial PET/CT scans at multiple time points during the first imaging visit to assess dosimetry and biodistribution. Data from 6 eligible participants with GRPR-positive lesion(s) will be used to determine the optimal administered activity and imaging time window for Phase 3, with the possibility of enrolling additional participants if warranted. Dosimetry will be estimated from imaging data collected during the dose optimization period and analyzed using standard, validated methodologies appropriate for PET radiopharmaceuticals. Dosimetry calculations will be performed using Organ Level Internal Dose Assessment (OLINDA). Image quality evaluation will include qualitative assessment by qualified image readers and quantitative assessment of tumor-to-background characteristics for lesions identified on PET/CT. Lesion(s) demonstrating uptake consistent with GRPR expression may be evaluated to support assessment of lesion conspicuity, contrast, and interpretability across evaluated imaging parameters. These exploratory evaluations will be used solely to support selection of the optimized administered activity and imaging time window. Phase 2 dosimetry, biodistribution, and image quality assessment data will not contribute to the Phase 3 primary diagnostic performance analyses. Phase 3 Diagnostic Performance Period The Phase 3 Diagnostic Performance Period is designed to evaluate the diagnostic accuracy of\[68Ga\]-LNTH-2401 PET/CT for detecting prostate cancer in pelvic lymph nodes (primary; compared to histopathology) and in other anatomic regions, as defined by study endpoints. All Phase 3 participants will undergo \[68Ga\]-LNTH-2401 PET/CT imaging using the optimized administered activity and imaging time window selected in Phase 2. Diagnostic accuracy will be assessed using local histopathological evaluation of surgically removed pelvic lymph nodes, or other anatomic regions (as applicable) as the primary standard of truth (SOT). The primary diagnostic performance endpoints are participant-level sensitivity and participant-level specificity of \[68Ga\]-LNTH-2401 PET/CT for detection of prostate cancer in pelvic lymph nodes, derived from pelvic lymph node region-level classifications compared with region-matched histopathology. Secondary diagnostic performance assessments will use a composite standard of truth (CSOT) incorporating histopathology and, where applicable, anatomic correlation with conventional imaging modalities and/or PSMA PET imaging. All imaging data will be reviewed by 3 blinded central readers, and the CSOT will be established by an Independent Committee in accordance with a predefined charter. Additionally, safety and tolerability will be evaluated following administration of \[⁶⁸Ga\]-LNTH-2401 using the Phase 2-selected imaging parameters. Regional detection performance across anatomic sites and assessment of the impact of \[68Ga\]-LNTH-2401 PET/CT imaging on intended clinical management will also be explored in the Phase 3 portion of the study.