Multiple Time-Point 68Ga-PSMA I&T PET/CT for Characterization of Primary Prostate Cancer: Value of Early Dynamic and Delayed Imaging

Purpose The aims of this study were to gain mechanistic insights into prostate cancer biology using dynamic imaging and to evaluate the usefulness of multiple time-point 68Ga–prostate-specific membrane antigen (PSMA) I&T PET/CT for the assessment of primary prostate cancer before prostatectomy. Methods Twenty patients with prostate cancer underwent 68Ga-PSMA I&T PET/CT before prostatectomy. The PET protocol consisted of early dynamic pelvic imaging, followed by static scans at 60 and 180 minutes postinjection (p.i.). SUVs, time-activity curves, quantitative analysis based on a 2-tissue compartment model, Patlak analysis, histopathology, and Gleason grading were compared between prostate cancer and benign prostate gland. Results Primary tumors were identified on both early dynamic and delayed imaging in 95% of patients. Tracer uptake was significantly higher in prostate cancer compared with benign prostate tissue at any time point (P ⩽ 0.0003) and increased over time. Consequently, the tumor-to-nontumor ratio within the prostate gland improved over time (2.8 at 10 minutes vs 17.1 at 180 minutes p.i.). Tracer uptake at both 60 and 180 minutes p.i. was significantly higher in patients with higher Gleason scores (P < 0.01). The influx rate (Ki) was higher in prostate cancer than in reference prostate gland (0.055 [r = 0.998] vs 0.017 [r = 0.996]). Conclusions Primary prostate cancer is readily identified on early dynamic and static delayed 68Ga-PSMA ligand PET images. The tumor-to-nontumor ratio in the prostate gland improves over time, supporting a role of delayed imaging for optimal visualization of prostate cancer.

[1]  B. Hadaschik,et al.  68Ga-PSMA-11 dynamic PET/CT imaging in biochemical relapse of prostate cancer , 2016, European Journal of Nuclear Medicine and Molecular Imaging.

[2]  C. Zamboglou,et al.  68Ga-HBED-CC-PSMA PET/CT Versus Histopathology in Primary Localized Prostate Cancer: A Voxel-Wise Comparison , 2016, Theranostics.

[3]  Michael Lassmann,et al.  68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies , 2015, The Journal of Nuclear Medicine.

[4]  B. Hadaschik,et al.  68Ga-PSMA-11 Dynamic PET/CT Imaging in Primary Prostate Cancer , 2016, Clinical nuclear medicine.

[5]  S. Koochekpour,et al.  Therapeutic Rationales, Progresses, Failures, and Future Directions for Advanced Prostate Cancer , 2016, International journal of biological sciences.

[6]  M. Schwaiger,et al.  Evaluation of Hybrid 68Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy , 2015, The Journal of Nuclear Medicine.

[7]  H. Wester,et al.  Cationic eluate pretreatment for automated synthesis of [⁶⁸Ga]CPCR4.2. , 2014, Nuclear medicine and biology.

[8]  C. Stief,et al.  68Ga-PSMA PET/CT Detects the Location and Extent of Primary Prostate Cancer , 2016, The Journal of Nuclear Medicine.

[9]  A. Buck,et al.  Biodistribution and Radiation Dosimetry for a Probe Targeting Prostate-Specific Membrane Antigen for Imaging and Therapy , 2015, The Journal of Nuclear Medicine.

[10]  V. Reuter,et al.  Prostate-specific membrane antigen is produced in tumor-associated neovasculature. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[11]  V. Lowe,et al.  Early detection of prostate cancer relapse by biochemistry and diagnostic imaging. , 2015, The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of....

[12]  C. Patlak,et al.  Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data. Generalizations , 1985, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[13]  U. Haberkorn,et al.  PSMA as a target for radiolabelled small molecules , 2013, European Journal of Nuclear Medicine and Molecular Imaging.

[14]  T. Holland-Letz,et al.  PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions , 2013, European Journal of Nuclear Medicine and Molecular Imaging.

[15]  E. Demirci,et al.  Evaluation of PSMA PET/CT imaging using a 68Ga-HBED-CC ligand in patients with prostate cancer and the value of early pelvic imaging , 2015, Nuclear medicine communications.

[16]  T. Momose,et al.  Noninvasive method to obtain input function for measuring tissue glucose utilization of thoracic and abdominal organs. , 1991, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[17]  Yuka Yamamoto,et al.  Dual-time-point 18F-FDG PET for the evaluation of gallbladder carcinoma. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[18]  M. Schwaiger,et al.  Diagnostic Efficacy of (68)Gallium-PSMA Positron Emission Tomography Compared to Conventional Imaging for Lymph Node Staging of 130 Consecutive Patients with Intermediate to High Risk Prostate Cancer. , 2016, The Journal of urology.

[19]  J. Ferlay,et al.  Prostate cancer incidence and mortality trends in 37 European countries: an overview. , 2010, European journal of cancer.

[20]  J. Quian,et al.  Expression of prostate specific membrane antigen (PSMA) in prostatic adenocarcinoma and prostatic intraepithelial neoplasia. , 2004, Histology and histopathology.

[21]  J. Bowie,et al.  A novel cytoplasmic tail MXXXL motif mediates the internalization of prostate-specific membrane antigen. , 2003, Molecular biology of the cell.

[22]  T. Holland-Letz,et al.  The diagnostic value of PET/CT imaging with the 68Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer , 2014, European Journal of Nuclear Medicine and Molecular Imaging.