TY - JOUR
T1 - Positron Emission Tomography/Computed Tomography with Gallium-68–labeled Prostate-specific Membrane Antigen Detects Relapse After Vascular-targeted Photodynamic Therapy in a Prostate Cancer Model
AU - Alvim, Ricardo
AU - Nagar, Karan
AU - Das, Sudeep
AU - Lebdai, Souhil
AU - Wong, Nathan
AU - Somma, Alexander
AU - Hughes, Christopher
AU - Thomas, Jasmine
AU - Monette, Sébastien
AU - Scherz, Avigdor
AU - Kim, Kwanghee
AU - Grimm, Jan
AU - Coleman, Jonathan A.
PY - 2021/3/30
Y1 - 2021/3/30
N2 - Background: Evaluating the efficacy of focal therapy for prostate cancer is limited by current approaches and may be improved with biological imaging techniques. Objective: We assessed whether positron emission tomography/computed tomography with gallium-68–labeled prostate-specific membrane antigen (68Ga-PSMA PET/CT) can be used to predict relapse after vascular-targeted photodynamic therapy (VTP). Design, setting, and participants: A total of 1 × 106 LNCaP cells were grafted subcutaneously in the flanks of 6–8–wk-old SCID mice. Of 24 mice with measurable tumors 6 wk after tumor implantation, 20 were treated with VTP (150 mW/cm2) to ablate the tumors. Blood prostate-specific antigen (PSA) levels were assessed, and ⁶⁸Ga-PSMA PET/CT images were performed 1 d before VTP and 1 and 4 wk after. Outcome measurements and statistical analysis: Local tumor relapse was evaluated by histology, and tumors were analyzed by prostate-specific membrane antigen (PSMA) and PSA immunohistochemistry. T tests and Kruskal-Wallis tests were used to determine significance. Results and limitations: Four weeks after VTP, 11 (65%) mice had complete responses and six (35%) had tumor relapses confirmed by histology (hematoxylin and eosin, and PSMA immunohistochemistry). All mice with local relapse had positive 68Ga-PSMA PET/CT findings 4 wk after VTP; all complete responders did not. One week after VTP, the relapse detection sensitivity of 68Ga-PSMA PET/CT was 75%, whereas the sensitivity of PSA was only 33%. Compared with controls, relapsed tumors had a three-fold reduction in the number of cells with strong PSA staining by immunohistochemistry (1.5% vs 4.5%; p = 0.01). Conclusions: In a preclinical prostate cancer model, we show that 68Ga-PSMA PET/CT can identify and predict relapse earlier than blood PSA level. These findings support further testing in clinical trials. Patient summary: Positron emission tomography/computed tomography with gallium-68–labeled prostate-specific membrane antigen may be used to follow and evaluate treatment outcomes in men who receive focal therapy for prostate cancer.
AB - Background: Evaluating the efficacy of focal therapy for prostate cancer is limited by current approaches and may be improved with biological imaging techniques. Objective: We assessed whether positron emission tomography/computed tomography with gallium-68–labeled prostate-specific membrane antigen (68Ga-PSMA PET/CT) can be used to predict relapse after vascular-targeted photodynamic therapy (VTP). Design, setting, and participants: A total of 1 × 106 LNCaP cells were grafted subcutaneously in the flanks of 6–8–wk-old SCID mice. Of 24 mice with measurable tumors 6 wk after tumor implantation, 20 were treated with VTP (150 mW/cm2) to ablate the tumors. Blood prostate-specific antigen (PSA) levels were assessed, and ⁶⁸Ga-PSMA PET/CT images were performed 1 d before VTP and 1 and 4 wk after. Outcome measurements and statistical analysis: Local tumor relapse was evaluated by histology, and tumors were analyzed by prostate-specific membrane antigen (PSMA) and PSA immunohistochemistry. T tests and Kruskal-Wallis tests were used to determine significance. Results and limitations: Four weeks after VTP, 11 (65%) mice had complete responses and six (35%) had tumor relapses confirmed by histology (hematoxylin and eosin, and PSMA immunohistochemistry). All mice with local relapse had positive 68Ga-PSMA PET/CT findings 4 wk after VTP; all complete responders did not. One week after VTP, the relapse detection sensitivity of 68Ga-PSMA PET/CT was 75%, whereas the sensitivity of PSA was only 33%. Compared with controls, relapsed tumors had a three-fold reduction in the number of cells with strong PSA staining by immunohistochemistry (1.5% vs 4.5%; p = 0.01). Conclusions: In a preclinical prostate cancer model, we show that 68Ga-PSMA PET/CT can identify and predict relapse earlier than blood PSA level. These findings support further testing in clinical trials. Patient summary: Positron emission tomography/computed tomography with gallium-68–labeled prostate-specific membrane antigen may be used to follow and evaluate treatment outcomes in men who receive focal therapy for prostate cancer.
UR - http://www.scopus.com/inward/record.url?scp=85067285203&partnerID=8YFLogxK
U2 - 10.1016/j.euf.2019.06.008
DO - 10.1016/j.euf.2019.06.008
M3 - Article
C2 - 31227464
AN - SCOPUS:85067285203
SN - 2405-4569
VL - 7
SP - 472
EP - 478
JO - European Urology Focus
JF - European Urology Focus
IS - 2
ER -