Imaging Efficacy of [18F]CTT1057 PET for the Detection of PSMA-Positive Tumors Using Histopathology as Standard of Truth: Results from the GuideView Phase 2/3 Prospective Multicenter Study

Abstract

[¹⁸F]CTT1057 is a highly selective prostate-specific membrane antigen (PSMA)-targeted PET radiotracer for prostate cancer (PCa) detection. This prospective study (GuideView, NCT04838626) evaluates the imaging efficacy of [¹⁸F]CTT1057 PET to detect PSMA-positive lesions against histopathology in patients with newly diagnosed, untreated, high-risk PCa. Methods: Between September 7, 2021, and October 26, 2023, 201 patients planned for radical prostatectomy were screened and 195 patients were enrolled. Of these, 184 patients received a median of 355 MBq (range, 195-400 MBq) of [¹⁸F]CTT1057 and underwent PET/CT 90 min (±30 min) later. Three masked central independent readers evaluated the images. Coprimary endpoints were patient-level sensitivity (including primary tumor and pelvic lymph nodes) and region-level specificity (including pelvic lymph nodes only) for detection of PSMA-positive lesions, using histopathology as the standard of truth. The lower-bound 95% CI needed to surpass 50% for patient-level sensitivity and 70% for region-level specificity. Success was defined as at least 2 of 3 central readers meeting these criteria. Secondary endpoints included the patient-level and region-level positive predictive value and accuracy, region-level sensitivity, inter- and intrareader variability, detection rate of distant metastasis, pharmacokinetics, and safety and tolerability assessments. Results: Of the 184 patients who received [¹⁸F]CTT1057, 172 patients were evaluable for efficacy. Among these, a median of 19 lymph nodes (interquartile range, 13.0-28.5 lymph nodes) were dissected per patient. Both coprimary endpoints were met, with lower bounds of 95% CIs surpassing the success criteria for all 3 readers for both patient-level sensitivity (range, 86.8%-90.0%; lower-bound 95% CI, 80.7%-84.5%) and region-level specificity (97.1%; lower-bound 95% CI, 92.7%). Interreader variability Fleiss κ was 63.9%; intrareader reproducibility Cohen κ was 89.4%-100%. [¹⁸F]CTT1057 had a favorable safety profile. Conclusion: GuideView confirmed the imaging efficacy of [¹⁸F]CTT1057 for the detection of PSMA-positive lesions, with high patient-level sensitivity and region-level specificity. Substantial interreader variability and almost perfect intrareader reproducibility suggest that [¹⁸F]CTT1057 findings are robust and reliable. [¹⁸F]CTT1057 will contribute to expanding access to PSMA PET imaging to properly diagnose and treat patients with PCa.

Keywords: PET; [18F]CTT1057; high-risk prostate cancer; molecular imaging; prostate-specific membrane antigen.

Graphical abstract

FIGURE 1.

Representative [¹⁸F]CTT1057 PET/CT scan cases showing true-positive lesions in PT among patients with different Gleason scores (arrows), with SUV_max ranges for each across 3 readers. Axial slices (left to right) show fused PET/CT scan, PET scan, and CT scan. (A) A 48-y-old patient (cT3a) with right prostate lesion (SUV_max, 10.1–12.8). (B) A 63-y-old patient (cT3a) with multiple prostate lesions (SUV_max, 6.8–10.6). (C) A 69-y-old patient (cT2a) showing left prostate lesion (SUV_max, 9.6–46.4; top row) with extension to left seminal vesicle (bottom row). (D) A 63-y-old patient (cT3) with left prostate lesion (SUV_max, 8.7–14). (E) A 77-y-old patient (cT2c) with right prostate lesion (SUV_max, 12.5–12.7). cT = clinical stage for PT; HU = Hounsfield units; PSA = prostate-specific antigen.

FIGURE 2.

Representative [¹⁸F]CTT1057 PET/CT scan case showing true-positive lesions in PT and PLN metastases in 63-y-old patient (PT clinical stage 3; Gleason score, 9 [4 + 5]; PSA, 14.2 ng/mL). Axial slices (left to right) show fused PET/CT scan, PET scan, and CT scan. (A) True-positive lesions in left prostate gland (SUV_max, 14; blue arrows). (B–E) True-positive lesions were seen in several PLNs (red arrows). (B) Right external iliac (SUV_max, 4.7). (C) Right internal iliac (SUV_max, 6.9) and left external iliac (SUV_max, 11.4). (D) Left external iliac (SUV_max, 10.2). (E) Presacral (SUV_max, 3.6). HU = Hounsfield units.