First-in-human evaluation of [<sup>18</sup>F]-AlF-NOTA-neurotensin for NTSR1-targeted imaging of prostate cancer: a head-to-head comparison with [<sup>68</sup>Ga]Ga-PSMA-617.
[<sup>68</sup>Ga]Ga-PSMA-617 is the preferred imaging agent for treatment-naïve prostate cancer, while [<sup>18</sup>F]-AlF-NOTA-neurotensin may be useful for enhancing detection after androgen-deprivation therapy.
Where it sits
this study against the rest of the leuprorelin corpusSummary and findings
This study evaluated the NTSR1-directed radiotracer [<sup>18</sup>F]-AlF-NOTA-neurotensin in comparison to [<sup>68</sup>Ga]Ga-PSMA-617 for imaging prostate cancer in 23 men. The findings indicated that [<sup>68</sup>Ga]Ga-PSMA-617 had superior sensitivity and specificity in treatment-naïve patients, while [<sup>18</sup>F]-AlF-NOTA-neurotensin showed improved sensitivity after short-term androgen-deprivation therapy.
Abstract
<h4>Background</h4>Neurotensin receptor-1 (NTSR1) is a promising target for prostate cancer imaging. This study evaluates the first-in-human NTSR1-directed radiotracer [<sup>18</sup>F]-AlF-NOTA-neurotensin and compares it with [<sup>68</sup>Ga]Ga-PSMA-617.<h4>Methods</h4>In a single-centre, prospective study, 23 men with biopsy-verified prostate cancer were enrolled at Xiangya Hospital (June 2020-June 2024). Within 7 days before radical prostatectomy, whole-body PET/CT was performed after sequential administration of [<sup>68</sup>Ga]Ga-PSMA-617 and [<sup>18</sup>F]-AlF-NOTA-neurotensin. Imaging metrics were assessed against histopathology. Immunohistochemistry (IHC) for PSMA and NTSR1 was conducted to correlate tracer uptake with receptor expression.<h4>Results</h4>The median age was 71 years (IQR 66-75); 14 were treatment-naïve and 9 had prior androgen-deprivation therapy (ADT). In untreated patients, [<sup>68</sup>Ga]Ga-PSMA-617 showed superior sensitivity (92.9%), specificity (100%), PPV (100%), and NPV (93.3%) compared to [<sup>18</sup>F]-AlF-NOTA-neurotensin . At the lesion level, [<sup>68</sup>Ga]Ga-PSMA-617 localized 36 of 38 foci (94.7%), while [<sup>18</sup>F]-AlF-NOTA-neurotensin identified none (0%; <i>p</i> < 0.05). After short-term ADT, [<sup>68</sup>Ga]Ga-PSMA-617 sensitivity dropped to 33.3%, while [<sup>18</sup>F]-AlF-NOTA-neurotensin sensitivity rose to 77.8% (<i>p</i> < 0.05). Lesion-based detection rates were 36% and 64%, respectively, and there were no significant differences in specificity, PPV, or NPV. IHC revealed a significant decrease in PSMA H-score from 9 (IQR 6.5-12) to 7 (IQR 1.3-8.8; <i>p</i> = 0.034) and an increase in NTSR1 H-score from 1 (IQR 0.25-2) to 6 (IQR 3-8; <i>p</i> = 0.003).<h4>Conclusion</h4>[<sup>68</sup>Ga]Ga-PSMA-617 remains the gold standard for treatment-naïve prostate cancer, whereas [<sup>18</sup>F]-AlF-NOTA-neurotensin provides complementary-diagnostic value by enhancing lesion detection after ADT. Our findings support a stage-adapted, receptor-driven imaging strategy that addresses tumor phenotypic heterogeneity, enabling more precise management throughout the disease course.
Background
The study addresses the evaluation of neurotensin receptor-1 (NTSR1) as a target for imaging prostate cancer, which is significant given the limitations of current imaging techniques. Prior knowledge indicated that [<sup>68</sup>Ga]Ga-PSMA-617 is the gold standard for prostate cancer imaging, but the potential role of NTSR1 in enhancing imaging after androgen-deprivation therapy (ADT) warranted investigation. This study aims to provide insights into the comparative effectiveness of these two radiotracers.
Methods
This was a single-center, prospective study involving 23 men with biopsy-verified prostate cancer, conducted from June 2020 to June 2024. Whole-body PET/CT imaging was performed within 7 days prior to radical prostatectomy after the administration of both radiotracers. The primary outcome measures included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) assessed against histopathology.
Results
The primary endpoint indicated that in treatment-naïve patients, [<sup>68</sup>Ga]Ga-PSMA-617 had a sensitivity of 92.9% and specificity of 100%. In contrast, [<sup>18</sup>F]-AlF-NOTA-neurotensin showed no detection of lesions (0%; p < 0.05). After ADT, the sensitivity of [<sup>68</sup>Ga]Ga-PSMA-617 decreased to 33.3%, while [<sup>18</sup>F]-AlF-NOTA-neurotensin's sensitivity increased to 77.8% (p < 0.05).
Interpretation
These findings suggest that while [<sup>68</sup>Ga]Ga-PSMA-617 remains superior for treatment-naïve patients, [<sup>18</sup>F]-AlF-NOTA-neurotensin may provide additional diagnostic value post-ADT. The significant drop in sensitivity for [<sup>68</sup>Ga]Ga-PSMA-617 after ADT raises questions about its reliability in this context. However, the small sample size and single-center design limit the robustness of these conclusions.
Key findings
- In untreated patients, [<sup>68</sup>Ga]Ga-PSMA-617 sensitivity was 92.9%, specificity was 100%, PPV was 100%, and NPV was 93.3%.
- [<sup>68</sup>Ga]Ga-PSMA-617 localized 36 of 38 foci (94.7%), while [<sup>18</sup>F]-AlF-NOTA-neurotensin identified none (0%; p < 0.05).
- After short-term ADT, [<sup>68</sup>Ga]Ga-PSMA-617 sensitivity dropped to 33.3%, while [<sup>18</sup>F]-AlF-NOTA-neurotensin sensitivity rose to 77.8% (p < 0.05).
- Lesion-based detection rates were 36% for [<sup>68</sup>Ga]Ga-PSMA-617 and 64% for [<sup>18</sup>F]-AlF-NOTA-neurotensin.
- The PSMA H-score decreased from 9 (IQR 6.5-12) to 7 (IQR 1.3-8.8; p = 0.034), while the NTSR1 H-score increased from 1 (IQR 0.25-2) to 6 (IQR 3-8; p = 0.003).
Limitations
- Single-center study limits generalizability.
- Small sample size of 23 men.
- Short follow-up period before radical prostatectomy.
- No blinding reported in the imaging assessment.