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 Journal Article


Authors: Alvim, R.; Nagar, K.; Das, S.; Lebdai, S.; Wong, N.; Somma, A.; Hughes, C.; Thomas, J.; Monette, S.; Scherz, A.; Kim, K.; Grimm, J.; Coleman, J. A.
Article Title: 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
Abstract: 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. © 2019 Positron emission tomography/computed tomography with gallium-68–labeled prostate-specific membrane antigen can predict tumor relapse after ablation by vascular-targeted photodynamic therapy earlier than blood prostate-specific antigen levels. This imaging technology may be a useful method to monitor patients with prostate cancer after they receive focal therapy. © 2019
Keywords: immunohistochemistry; treatment outcome; unclassified drug; histopathology; cancer recurrence; nonhuman; positron emission tomography; sensitivity and specificity; animal cell; mouse; animal tissue; animal experiment; animal model; prediction; prostate cancer; staining; radiopharmaceutical agent; eosin; hematoxylin; photodynamic therapy; scid mouse; predictive value; cancer transplantation; focal therapy; prostate-specific membrane antigen; male; article; lncap cell line; prostate ablation; vascular-targeted photodynamic therapy; positron emission tomography-computed tomography; padeliporfin; positron emission tomography/computed tomography with gallium-68–labeled prostate-specific membrane antigen; tookad; prostate specific membrane antigen gallium ga 68
Journal Title: European Urology Focus
Volume: 7
Issue: 2
ISSN: 2405-4569
Publisher: Elsevier B.V.  
Date Published: 2021-03-01
Start Page: 472
End Page: 478
Language: English
DOI: 10.1016/j.euf.2019.06.008
PUBMED: 31227464
PROVIDER: scopus
PMCID: PMC7032651
DOI/URL:
Notes: Article -- Export Date: 3 May 2021 -- Source: Scopus
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MSK Authors
  1. Jonathan Coleman
    341 Coleman
  2. Sebastien Monette
    148 Monette
  3. Jan Grimm
    93 Grimm
  4. Sudeep Das
    7 Das
  5. Kwanghee   Kim
    43 Kim
  6. Alexander Joseph Somma
    10 Somma
  7. Souhil Lebdai
    5 Lebdai
  8. Ricardo Goncalves Alvim
    25 Alvim
  9. Karan K Nagar
    13 Nagar
  10. Christopher Hughes
    4 Hughes
  11. Nathan Colin Wong
    25 Wong
  12. Jasmine Thomas
    11 Thomas