Initial Experience with Volumetric 68Ga-PSMA I&T PET/CT for Assessment of Whole-Body Tumor Burden as a Quantitative Imaging Biomarker in Patients with Prostate Cancer

A quantitative imaging biomarker is desirable to provide a comprehensive measure of whole-body tumor burden in patients with metastatic prostate cancer, and to standardize the evaluation of treatment-related changes. Therefore, we evaluated whether prostate-specific membrane antigen (PSMA) ligand PET/CT may be applied to provide PSMA-derived volumetric parameters for quantification of whole-body tumor burden. Methods: One hundred one patients who underwent 68Ga-PSMA I&T PET/CT because of increasing prostate-specific antigen (PSA) levels after radical prostatectomy were included in this retrospective analysis. Tracer uptake was quantified using SUVs. Volumetric parameters, that is, PSMA-derived tumor volume (PSMA-TV) and total lesion PSMA (TL-PSMA), were calculated for each patient using a 3-dimensional segmentation and computerized volumetry technique and compared with serum PSA levels. In a group of 10 patients, volumetric parameters were applied for treatment monitoring. Results: Volumetric parameters, that is, whole-body PSMA-TV and whole-body TL-PSMA, demonstrated a statistically significant correlation with PSA levels (P < 0.0001) as a surrogate marker of tumor burden, whereas SUVmax (P = 0.22) or SUVmean (P = 0.45) did not. Treatment response and treatment failure were paralleled by concordant changes in both whole-body PSMA-TV and whole-body TL-PSMA (P = 0.02), whereas neither the change in SUVmax (P = 1.0) nor the change in SUVmean (P = 1.0) concordantly paralleled changes in PSA levels. Conclusion: PSMA-derived volumetric parameters provide a quantitative imaging biomarker for whole-body tumor burden, capable of standardizing quantitative changes in PET imaging of patients with metastatic prostate cancer and of facilitating therapy monitoring.

[1]  L. Schwartz,et al.  New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). , 2009, European journal of cancer.

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

[3]  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.

[4]  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.

[5]  Rosalie Nolley,et al.  The prostate specific antigen era in the United States is over for prostate cancer: what happened in the last 20 years? , 2004, The Journal of urology.

[6]  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.

[7]  Tobias L Ross,et al.  Multiple Time-Point 68Ga-PSMA I&T PET/CT for Characterization of Primary Prostate Cancer: Value of Early Dynamic and Delayed Imaging , 2017, Clinical nuclear medicine.

[8]  A. Drzezga,et al.  PSA-Stratified Performance of 18F- and 68Ga-PSMA PET in Patients with Biochemical Recurrence of Prostate Cancer , 2017, The Journal of Nuclear Medicine.

[9]  S. Barrington,et al.  Combination of baseline metabolic tumour volume and early response on PET/CT improves progression-free survival prediction in DLBCL , 2016, European Journal of Nuclear Medicine and Molecular Imaging.

[10]  Eva Forssell-Aronsson,et al.  Modelling of metastatic cure after radionuclide therapy: influence of tumor distribution, cross-irradiation, and variable activity concentration. , 2004, Medical physics.

[11]  L. Edenbrandt,et al.  Bone Scan Index predicts outcome in patients with metastatic hormone‐sensitive prostate cancer , 2016, BJU international.

[12]  Mattias Ohlsson,et al.  A novel automated platform for quantifying the extent of skeletal tumour involvement in prostate cancer patients using the Bone Scan Index. , 2012, European urology.

[13]  T. Derlin,et al.  Comparison of standard and delayed imaging to improve the detection rate of [68Ga]PSMA I&T PET/CT in patients with biochemical recurrence or prostate-specific antigen persistence after primary therapy for prostate cancer , 2017, European Journal of Nuclear Medicine and Molecular Imaging.

[14]  Donna L Berry,et al.  Intermittent versus continuous androgen deprivation in prostate cancer. , 2013, The New England journal of medicine.

[15]  I. Apostolova,et al.  Nerve Sheath Tumors in Neurofibromatosis Type 1: Assessment of Whole-Body Metabolic Tumor Burden Using F-18-FDG PET/CT , 2015, PloS one.

[16]  M. Schwaiger,et al.  Simultaneous 68Ga-PSMA HBED-CC PET/MRI Improves the Localization of Primary Prostate Cancer. , 2016, European urology.

[17]  D. Fried,et al.  The value of 18F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma , 2016, European Journal of Nuclear Medicine and Molecular Imaging.

[18]  M. Biermann,et al.  Metabolic Tumor Volume on 18F-FDG PET/CT Improves Preoperative Identification of High-Risk Endometrial Carcinoma Patients , 2015, The Journal of Nuclear Medicine.

[19]  A. Haese*,et al.  High level PSMA expression is associated with early psa recurrence in surgically treated prostate cancer , 2011, The Prostate.

[20]  M. Schwaiger,et al.  Value of 68Ga-PSMA HBED-CC PET for the Assessment of Lymph Node Metastases in Prostate Cancer Patients with Biochemical Recurrence: Comparison with Histopathology After Salvage Lymphadenectomy , 2016, The Journal of Nuclear Medicine.

[21]  R. Boellaard,et al.  Repeatability of Quantitative 18F-Fluoromethylcholine PET/CT Studies in Prostate Cancer , 2016, The Journal of Nuclear Medicine.

[22]  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.

[23]  M. Picchio,et al.  Radiation Treatment of Lymph Node Recurrence from Prostate Cancer: Is 11C-Choline PET/CT Predictive of Survival Outcomes? , 2015, The Journal of Nuclear Medicine.

[24]  David F Jarrard,et al.  Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. , 2015, The New England journal of medicine.

[25]  E. Varenhorst,et al.  The impact of prostate‐specific antigen level at diagnosis on the relative survival of 28,531 men with localized carcinoma of the prostate , 2008, Cancer.

[26]  J. Oesterling,et al.  Prostate specific antigen in the staging of localized prostate cancer: influence of tumor differentiation, tumor volume and benign hyperplasia. , 1990, The Journal of urology.

[27]  T. Derlin,et al.  68Ga-PSMA I&T PET/CT for assessment of prostate cancer: evaluation of image quality after forced diuresis and delayed imaging , 2016, European Radiology.

[28]  D. Beyersdorff,et al.  Detection rate of PET/CT in patients with biochemical relapse of prostate cancer using [68Ga]PSMA I&T and comparison with published data of [68Ga]PSMA HBED-CC , 2017, European Journal of Nuclear Medicine and Molecular Imaging.

[29]  H. Grönberg,et al.  Comparison Between the Four-kallikrein Panel and Prostate Health Index for Predicting Prostate Cancer. , 2015, European urology.