Evaluation of 177Lu-PSMA-617 SPECT/CT Quantitation as a Response Biomarker Within a Prospective 177Lu-PSMA-617 and NOX66 Combination Trial (LuPIN)
Journal Title
Journal of Nuclear Medicine
Publication Type
Research article
Abstract
(177)Lu-PSMA-617 is an effective and novel treatment in metastatic castration-resistant prostate cancer (mCRPC). Our ability to assess response rates and therefore efficacy may be improved using predictive tools. This study investigated the predictive value of serial (177)Lu-PSMA-617 SPECT/CT ((177)Lu SPECT) imaging in monitoring treatment response. Methods: Fifty-six men with progressive mCRPC previously treated with chemotherapy and novel androgen signaling inhibitor were enrolled into the LuPIN trial and received up to 6 doses of (177)Lu-PSMA-617 and a radiation sensitizer (3-(4-hydroxyphenyl)-2H-1-benzopyran-7-ol [NOX66]). (68)Ga-PSMA-11 and (18)F-FDG PET/CT were performed at study entry and exit, and (177)Lu SPECT from vertex to mid thighs was performed 24 h after each treatment. SPECT quantitative analysis was undertaken at cycles 1 (baseline) and 3 (week 12) of treatment. Results: Thirty-two of the 56 men had analyzable serial (177)Lu SPECT imaging at both cycle 1 and cycle 3. In this subgroup, median prostate-specific antigen (PSA) progression-free survival (PFS) was 6.3 mo (95% CI, 5-10 mo) and median overall survival was 12.3 mo (95% CI, 12-24 mo). The PSA 50% response rate was 63% (20/32). (177)Lu SPECT total tumor volume (SPECT TTV) was reduced in 68% (22/32; median, -0.20 m(3) [95% CI, -1.4 to -0.001]) and increased in 31% (10/32; median, 0.36 [95% CI, 0.1-1.4]). Any increase in SPECT TTV was associated with shorter PSA PFS (hazard ratio, 4.1 [95% CI, 1.5-11.2]; P = 0.006). An increase of 30% or more in SPECT TTV was also associated with a shorter PSA PFS (hazard ratio, 3.3 [95% CI, 1.3-8.6]; P =0.02). Tumoral SUV(max) was reduced in 91% (29/32) and SUV(mean) in 84% (27/32); neither was associated with PSA PFS or overall survival outcomes. PSA progression by week 12 was also associated with a shorter PSA PFS (hazard ratio, 26.5 [95% CI, 5.4-131]). In the patients with SPECT TTV progression at week 12, 50% (5/10) had no concurrent PSA progression (median PSA PFS, 4.5 mo [95% CI, 2.8-5.6 mo]), and 5 of 10 men had both PSA and SPECT TTV progression at week 12 (median PSA PFS, 2.8 mo [95% CI, 1.8-3.7 mo]). Conclusion: Increasing SPECT TTV on quantitative (177)Lu SPECT predicts a short PFS and may play a future role as an imaging response biomarker.
Publisher
Society of Nuclear Medicine and Molecular Imaging
Keywords
Male; Humans; *Prostate-Specific Antigen; Treatment Outcome; Positron Emission Tomography Computed Tomography; *Prostatic Neoplasms, Castration-Resistant/diagnostic imaging/radiotherapy/drug; therapy; Prospective Studies; Radiopharmaceuticals/therapeutic use; Dipeptides/therapeutic use; Heterocyclic Compounds, 1-Ring/therapeutic use; Single Photon Emission Computed Tomography Computed Tomography; Lutetium/therapeutic use
Department(s)
Cancer Imaging
PubMed ID
36008120
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Refer to copyright notice on published article.


Creation Date: 2023-06-13 07:55:10
Last Modified: 2023-06-13 07:56:08

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