Review Article| Volume 50, ISSUE 1, P115-131, February 2023

Targeted Molecular Imaging as a Biomarker in Urologic Oncology

  • Arvin Haj-Mirzaian
    Department of Radiology, Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, 55 Fruit St, Wht 427, Boston, MA 02114, USA

    Center for Precision Imaging, Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 55 Fruit St, Wht 427, Boston, MA 02114, USA
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  • Umar Mahmood
    Corresponding author.
    Department of Radiology, Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, 55 Fruit St, Wht 427, Boston, MA 02114, USA

    Center for Precision Imaging, Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 55 Fruit St, Wht 427, Boston, MA 02114, USA
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  • Pedram Heidari
    Department of Radiology, Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, 55 Fruit St, Wht 427, Boston, MA 02114, USA

    Center for Precision Imaging, Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 55 Fruit St, Wht 427, Boston, MA 02114, USA
    Search for articles by this author


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        • Dy G.W.
        • Gore J.L.
        • Forouzanfar M.H.
        • et al.
        Global burden of urologic cancers, 1990–2013.
        Eur Urol. 2017; 71: 437-446
        • Savir-Baruch B.
        • Werner R.A.
        • Rowe S.P.
        • et al.
        PET imaging for prostate cancer.
        Radiologic Clin. 2021; 59: 801-811
        • Sharma S.
        • Zapatero-Rodriguez J.
        • O'Kennedy R.
        Prostate cancer diagnostics: Clinical challenges and the ongoing need for disruptive and effective diagnostic tools.
        Biotechnol Adv. 2017; 35: 135-149
        • Picchio M.
        • Mapelli P.
        • Panebianco V.
        • et al.
        Imaging biomarkers in prostate cancer: role of PET/CT and MRI.
        Eur J Nucl Med Mol Imaging. 2015; 42: 644-655
        • Wibmer A.G.
        • Burger I.A.
        • Sala E.
        • et al.
        Molecular imaging of prostate cancer.
        Radiographics. 2016; 36: 142
        • Mhawech-Fauceglia P.
        • Zhang S.
        • Terracciano L.
        • et al.
        Prostate-specific membrane antigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivity and specificity in prostate adenocarcinoma: an immunohistochemical study using multiple tumour tissue microarray technique.
        Histopathology. 2007; 50: 472-483
        • Ferreira G.
        • Iravani A.
        • Hofman M.S.
        • et al.
        Intra-individual comparison of 68 Ga-PSMA-11 and 18 F-DCFPyL normal-organ biodistribution.
        Cancer Imaging. 2019; 19: 1-10
        • von Eyben F.E.
        • Picchio M.
        • von Eyben R.
        • et al.
        68Ga-labeled prostate-specific membrane antigen ligand positron emission tomography/computed tomography for prostate cancer: a systematic review and meta-analysis.
        Eur Urol focus. 2018; 4: 686-693
        • Uprimny C.
        • Kroiss A.S.
        • Decristoforo C.
        • et al.
        68Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour.
        Eur J Nucl Med Mol Imaging. 2017; 44: 941-949
        • Peng L.
        • Li J.
        • Meng C.
        • et al.
        Can 68Ga-prostate specific membrane antigen positron emission tomography/computerized tomography provide an accurate lymph node staging for patients with medium/high risk prostate cancer? A diagnostic meta-analysis.
        Radiat Oncol. 2020; 15: 1-10
        • Zhao R.
        • Li Y.
        • Nie L.
        • et al.
        The meta-analysis of the effect of 68Ga-PSMA-PET/CT diagnosis of prostatic cancer compared with bone scan.
        Medicine. 2021; 100
        • Manafi-Farid R.
        • Ranjbar S.
        • Jamshidi Araghi Z.
        • et al.
        Molecular Imaging in Primary Staging of Prostate Cancer Patients: Current Aspects and Future Trends.
        Cancers. 2021; 13: 5360
        • Morris M.J.
        • Rowe S.P.
        • Gorin M.A.
        • et al.
        Diagnostic performance of 18F-DCFPyL-PET/CT in men with biochemically recurrent prostate cancer: Results from the CONDOR phase III, multicenter study.
        Clin Cancer Res. 2021; 27: 3674-3682
        • Pienta K.J.
        • Gorin M.A.
        • Rowe S.P.
        • et al.
        A phase 2/3 prospective multicenter study of the diagnostic accuracy of prostate specific membrane antigen PET/CT with 18F-DCFPyL in prostate cancer patients (OSPREY).
        J Urol. 2021; 206: 52-61
        • Sun J.
        • Lin Y.
        • Wei X.
        • et al.
        Performance of 18F-DCFPyL PET/CT Imaging in Early Detection of Biochemically Recurrent Prostate Cancer: A Systematic Review and Meta-Analysis.
        Front Oncol. 2021; 11: 649171
        • Awenat S.
        • Piccardo A.
        • Carvoeiras P.
        • et al.
        Diagnostic role of 18F-PSMA-1007 PET/CT in prostate cancer staging: a systematic review.
        Diagnostics. 2021; 11: 552
        • Giesel F.L.
        • Hadaschik B.
        • Cardinale J.
        • et al.
        F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients.
        Eur J Nucl Med Mol Imaging. 2017; 44: 678-688
        • Manyak M.J.
        • Hinkle G.H.
        • Olsen J.O.
        • et al.
        Immunoscintigraphy with indium-111-capromab pendetide: evaluation before definitive therapy in patients with prostate cancer.
        Urology. 1999; 54: 1058-1063
        • Morris M.J.
        • Pandit-Taskar N.
        • Carrasquillo J.A.
        • et al.
        Phase I trial of zirconium 89 (Zr89) radiolabeled J591 in metastatic castration-resistant prostate cancer (mCRPC).
        Journal of Clinical Oncology. 2013; 31: 31
        • Bratanovic I.J.
        • Zhang C.
        • Zhang Z.
        • et al.
        A Radiotracer for Molecular Imaging and Therapy of Gastrin-Releasing Peptide Receptor–Positive Prostate Cancer.
        J Nucl Med. 2022; 63: 424-430
        • Kähkönen E.
        • Jambor I.
        • Kemppainen J.
        • et al.
        In vivo imaging of prostate cancer using [68Ga]-labeled bombesin analog BAY86-7548.
        Clin Cancer Res. 2013; 19: 5434-5443
        • Touijer K.A.
        • Michaud L.
        • Alvarez H.A.V.
        • et al.
        Prospective study of the radiolabeled GRPR antagonist BAY86-7548 for positron emission tomography/computed tomography imaging of newly diagnosed prostate cancer.
        Eur Urol Oncol. 2019; 2: 166-173
        • Stephens A.
        • Loidl W.C.
        • Beheshti M.
        • et al.
        Detection of prostate cancer with the [68Ga]-labeled bombesin antagonist RM2 in patients undergoing radical prostatectomy.
        Journal of Clinical Oncology. 2016; 34: 80
        • Baratto L.
        • Song H.
        • Duan H.
        • et al.
        A prospective study of 68Ga-RM2 PET/MRI in patients with biochemically recurrent prostate cancer and negative conventional imaging.
        Journal of Clinical Oncology. 2020; 38: e17536
        • Parihar A.S.
        • Schmidt L.R.
        • Dehdashti F.
        • et al.
        Detection of additional primary neoplasms on 18F-Fluciclovine PET/CT in patients with primary prostate cancer.
        J Nucl Med. 2021; 63: 713-719
        • Laudicella R.
        • Albano D.
        • Alongi P.
        • et al.
        18F-Facbc in prostate cancer: a systematic review and meta-analysis.
        Cancers. 2019; 11: 1348
        • Gusman M.
        • Aminsharifi J.A.
        • Peacock J.G.
        • et al.
        Review of 18F-fluciclovine PET for detection of recurrent prostate cancer.
        Radiographics. 2019; 39: 822-841
        • Calais J.
        • Ceci F.
        • Eiber M.
        • et al.
        18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial.
        Lancet Oncol. 2019; 20: 1286-1294
        • Wallitt K.L.
        • Khan S.R.
        • Dubash S.
        • et al.
        Clinical PET imaging in prostate cancer.
        Radiographics. 2017; 37: 1512-1536
        • Jadvar H.
        Is There Use for FDG-PET in Prostate Cancer?.
        Semin Nucl Med. 2016; 46: 502-506
        • Bertagna F.
        • Sadeghi R.
        • Giovanella L.
        • et al.
        Incidental uptake of 18F-fluorodeoxyglucose in the prostate gland.
        Nuklearmedizin-NuclearMedicine. 2014; 53: 249-258
        • Shen K.
        • Liu B.
        • Zhou X.
        • et al.
        The evolving role of 18F-FDG PET/CT in diagnosis and prognosis prediction in progressive prostate cancer.
        Front Oncol. 2021; 11: 683793
        • Woitek R.
        • Gallagher F.A.
        The use of hyperpolarised 13C-MRI in clinical body imaging to probe cancer metabolism.
        Br J Cancer. 2021; 124: 1187-1198
        • Sushentsev N.
        • McLean M.A.
        • Warren A.Y.
        • et al.
        Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.
        Nat Commun. 2022; 13: 1-12
        • Chen H.-Y.
        • Aggarwal R.
        • Bok R.A.
        • et al.
        Hyperpolarized 13C-pyruvate MRI detects real-time metabolic flux in prostate cancer metastases to bone and liver: a clinical feasibility study.
        Prostate Cancer prostatic Dis. 2020; 23: 269-276
        • Jadvar H.
        Prostate cancer: PET with 18F-FDG, 18F-or 11C-acetate, and 18F-or 11C-choline.
        J Nucl Med. 2011; 52: 81-89
        • Evangelista L.
        • Cervino A.R.
        • Burei M.
        • et al.
        Comparative studies of radiolabeled choline positron emission tomography, histology of primary tumor and other imaging modalities in prostate cancer: a systematic review and meta-analysis.
        Clin Translational Imaging. 2013; 1: 99-109
        • Kato T.
        • Tsukamoto E.
        • Kuge Y.
        • et al.
        Accumulation of [11C] acetate in normal prostate and benign prostatic hyperplasia: comparison with prostate cancer.
        Eur J Nucl Med Mol Imaging. 2002; 29: 1492-1495
        • Mohsen B.
        • Giorgio T.
        • Rasoul Z.S.
        • et al.
        Application of C-11-acetate positron-emission tomography (PET) imaging in prostate cancer: systematic review and meta-analysis of the literature.
        BJU Int. 2013; 112: 1062-1072
        • Haseebuddin M.
        • Dehdashti F.
        • Siegel B.A.
        • et al.
        11C-acetate PET/CT before radical prostatectomy: nodal staging and treatment failure prediction.
        J Nucl Med. 2013; 54: 699-706
        • Strandberg S.
        • Karlsson C.T.
        • Ogren M.
        • et al.
        11C-acetate-PET/CT compared to 99mTc-HDP bone Scintigraphy in primary staging of high-risk prostate cancer.
        Anticancer Res. 2016; 36: 6475-6479
        • Beheshti M.
        • Rezaee A.
        • Geinitz H.
        • et al.
        Evaluation of prostate cancer bone metastases with 18F-NaF and 18F-fluorocholine PET/CT.
        J Nucl Med. 2016; 57: 55S-60S
        • Sheikhbahaei S.
        • Jones K.M.
        • Werner R.A.
        • et al.
        18F-NaF-PET/CT for the detection of bone metastasis in prostate cancer: a meta-analysis of diagnostic accuracy studies.
        Ann Nucl Med. 2019; 33: 351-361
        • Gauthé M.
        • Sargos P.
        • Barret E.
        • et al.
        Potential Targets Other Than PSMA for Prostate Cancer Theranostics: A Systematic Review.
        J Clin Med. 2021; 10: 4909
        • Vargas H.A.
        • Wassberg C.
        • Fox J.J.
        • et al.
        Bone metastases in castration-resistant prostate cancer: associations between morphologic CT patterns, glycolytic activity, and androgen receptor expression on PET and overall survival.
        Radiology. 2014; 271: 220-229
        • Larson S.M.
        • Morris M.
        • Gunther I.
        • et al.
        Tumor localization of 16β-18F-fluoro-5α-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer.
        J Nucl Med. 2004; 45: 366-373
        • Dehdashti F.
        • Picus J.
        • Michalski J.M.
        • et al.
        Positron tomographic assessment of androgen receptors in prostatic carcinoma.
        Eur J Nucl Med Mol Imaging. 2005; 32: 344-350
        • Persson M.
        • Skovgaard D.
        • Brandt-Larsen M.
        • et al.
        First-in-human uPAR PET: imaging of cancer aggressiveness.
        Theranostics. 2015; 5: 1303
        • Fosbøl M.Ø.
        • Kurbegovic S.
        • Johannesen H.H.
        • et al.
        Urokinase-type plasminogen activator receptor (uPAR) PET/MRI of prostate cancer for noninvasive evaluation of aggressiveness: comparison with Gleason score in a prospective phase 2 clinical trial.
        J Nucl Med. 2021; 62: 354-359
        • Zheng D.-Q.
        • Woodard A.S.
        • Fornaro M.
        • et al.
        Prostatic carcinoma cell migration via αvβ3integrin is modulated by a focal adhesion kinase pathway.
        Cancer Res. 1999; 59: 1655-1664
        • Beer A.J.
        • Schwarzenböck S.M.
        • Zantl N.
        • et al.
        Non-invasive assessment of inter-and intrapatient variability of integrin expression in metastasized prostate cancer by PET.
        Oncotarget. 2016; 7: 28151
        • Klinkhammer B.M.
        • Lammers T.
        • Mottaghy F.M.
        • et al.
        Non-invasive molecular imaging of kidney diseases.
        Nat Rev Nephrol. 2021; 17: 688-703
        • Stillebroer A.B.
        • Mulders P.F.
        • Boerman O.C.
        • et al.
        Carbonic anhydrase IX in renal cell carcinoma: implications for prognosis, diagnosis, and therapy.
        Eur Urol. 2010; 58: 75-83
        • van Oostenbrugge T.
        • Mulders P.
        Targeted PET/CT imaging for clear cell renal cell carcinoma with radiolabeled antibodies: recent developments using girentuximab.
        Curr Opin Urol. 2021; 31: 249-254
        • Divgi C.R.
        • Pandit-Taskar N.
        • Jungbluth A.A.
        • et al.
        Preoperative characterisation of clear-cell renal carcinoma using iodine-124-labelled antibody chimeric G250 (124I-cG250) and PET in patients with renal masses: a phase I trial.
        Lancet Oncol. 2007; 8: 304-310
        • van Oostenbrugge T.J.
        • Langenhuijsen J.F.
        • Oosterwijk E.
        • et al.
        Follow-up imaging after cryoablation of clear cell renal cell carcinoma is feasible using single photon emission computed tomography with 111In-girentuximab.
        Eur J Nucl Med Mol Imaging. 2020; 47: 1864-1870
        • Hekman M.C.
        • Rijpkema M.
        • Aarntzen E.H.
        • et al.
        Positron emission tomography/computed tomography with 89Zr-girentuximab can aid in diagnostic dilemmas of clear cell renal cell carcinoma suspicion.
        Eur Urol. 2018; 74: 257-260
        • Turkbey B.
        • Lindenberg M.L.
        • Adler S.
        • et al.
        PET/CT imaging of renal cell carcinoma with 18F-VM4-037: a phase II pilot study.
        Abdom Radiol. 2016; 41: 109-118
        • Tabei T.
        • Nakaigawa N.
        • Kaneta T.
        • et al.
        Early assessment with 18 F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography to predict short-term outcome in clear cell renal carcinoma treated with nivolumab.
        BMC cancer. 2019; 19: 1-9
        • Wang H.-Y.
        • Ding H.-J.
        • Chen J.-H.
        • et al.
        Meta-analysis of the diagnostic performance of [18F] FDG-PET and PET/CT in renal cell carcinoma.
        Cancer Imaging. 2012; 12: 464
        • Hwang S.H.
        • Cho A.
        • Yun M.
        • et al.
        Prognostic value of pretreatment metabolic tumor volume and total lesion glycolysis using 18F-FDG PET/CT in patients with metastatic renal cell carcinoma treated with anti–vascular endothelial growth factor–targeted agents.
        Clin Nucl Med. 2017; 42: e235-e241
        • Rowe S.P.
        • Gorin M.A.
        • Hammers H.J.
        • et al.
        Imaging of metastatic clear cell renal cell carcinoma with PSMA-targeted 18F-DCFPyL PET/CT.
        Ann Nucl Med. 2015; 29: 877-882
        • Yin Y.
        • Campbell S.P.
        • Markowski M.C.
        • et al.
        Inconsistent detection of sites of metastatic non-clear cell renal cell carcinoma with PSMA-targeted [18F] DCFPyL PET/CT.
        Mol Imaging Biol. 2019; 21: 567-573
        • Sawicki L.M.
        • Buchbender C.
        • Boos J.
        • et al.
        Diagnostic potential of PET/CT using a 68Ga-labelled prostate-specific membrane antigen ligand in whole-body staging of renal cell carcinoma: initial experience.
        Eur J Nucl Med Mol Imaging. 2017; 44: 102-107
        • Tang S.
        • Meng M.V.
        • Slater J.B.
        • et al.
        Metabolic imaging with hyperpolarized 13C pyruvate magnetic resonance imaging in patients with renal tumors—Initial experience.
        Cancer. 2021; 127: 2693-2704
        • Ursprung S.
        • Woitek R.
        • McLean M.A.
        • et al.
        Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma—A Proof of Principle Study.
        Cancers. 2022; 14: 335
        • Nakanishi Y.
        • Kitajima K.
        • Yamada Y.
        • et al.
        Diagnostic performance of 11C-choline PET/CT and FDG PET/CT for staging and restaging of renal cell cancer.
        Ann Nucl Med. 2018; 32: 658-668
        • Liu G.
        • Jeraj R.
        • Vanderhoek M.
        • et al.
        Pharmacodynamic study using FLT PET/CT in patients with renal cell cancer and other solid malignancies treated with sunitinib malate.
        Clin Cancer Res. 2011; 17: 7634-7644
        • Horn K.P.
        • Yap J.T.
        • Agarwal N.
        • et al.
        FDG and FLT-PET for early measurement of response to 37.5 mg daily sunitinib therapy in metastatic renal cell carcinoma.
        Cancer Imaging. 2015; 15: 1-10
        • Gerety E.
        • Lawrence E.
        • Wason J.
        • et al.
        Prospective study evaluating the relative sensitivity of 18F-NaF PET/CT for detecting skeletal metastases from renal cell carcinoma in comparison to multidetector CT and 99mTc-MDP bone scintigraphy, using an adaptive trial design.
        Ann Oncol. 2015; 26: 2113-2118
        • Desar I.M.
        • Stillebroer A.B.
        • Oosterwijk E.
        • et al.
        111In-bevacizumab imaging of renal cell cancer and evaluation of neoadjuvant treatment with the vascular endothelial growth factor receptor inhibitor sorafenib.
        J Nucl Med. 2010; 51: 1707-1715
        • van Es S.C.
        • Brouwers A.H.
        • Mahesh S.V.
        • et al.
        89Zr-bevacizumab PET: potential early indicator of everolimus efficacy in patients with metastatic renal cell carcinoma.
        J Nucl Med. 2017; 58: 905-910
        • Withofs N.
        • Signolle N.
        • Somja J.
        • et al.
        18F-FPRGD2 PET/CT imaging of integrin αvβ3 in renal carcinomas: correlation with histopathology.
        J Nucl Med. 2015; 56: 361-364
        • Mena E.
        • Owenius R.
        • Turkbey B.
        • et al.
        [18F] Fluciclatide in the in vivo evaluation of human melanoma and renal tumors expressing αvβ3 and αvβ5 integrins.
        Eur J Nucl Med Mol Imaging. 2014; 41: 1879-1888
        • Soubra A.
        • Hayward D.
        • Dahm P.
        • et al.
        The diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography and computed tomography in staging bladder cancer: a single-institution study and a systematic review with meta-analysis.
        World J Urol. 2016; 34: 1229-1237
        • Crozier J.
        • Papa N.
        • Perera M.
        • et al.
        Comparative sensitivity and specificity of imaging modalities in staging bladder cancer prior to radical cystectomy: a systematic review and meta-analysis.
        World J Urol. 2019; 37: 667-690
        • Ha H.K.
        • Koo P.J.
        • Kim S.-J.
        Diagnostic accuracy of F-18 FDG PET/CT for preoperative lymph node staging in newly diagnosed bladder cancer patients: a systematic review and meta-analysis.
        Oncology. 2018; 95: 31-38
        • Soubra A.
        • Gencturk M.
        • Froelich J.
        • et al.
        FDG-PET/CT for assessing the response to neoadjuvant chemotherapy in bladder cancer patients.
        Clin Genitourinary Cancer. 2018; 16: 360-364
        • Zattoni F.
        • Incerti E.
        • Colicchia M.
        • et al.
        Comparison between the diagnostic accuracies of 18F-fluorodeoxyglucose positron emission tomography/computed tomography and conventional imaging in recurrent urothelial carcinomas: a retrospective, multicenter study.
        Abdom Radiol. 2018; 43: 2391-2399
        • Kim S.-J.
        • Koo P.J.
        • Pak K.
        • et al.
        Diagnostic accuracy of C-11 choline and C-11 acetate for lymph node staging in patients with bladder cancer: a systematic review and meta-analysis.
        World J Urol. 2018; 36: 331-340
        • Schöder H.
        • Ong S.C.
        • Reuter V.E.
        • et al.
        Initial results with 11C-acetate positron emission tomography/computed tomography (PET/CT) in the staging of urinary bladder cancer.
        Mol Imaging Biol. 2012; 14: 245-251
        • Treglia G.
        • Sadeghi R.
        • Annunziata S.
        • et al.
        Diagnostic performance of fluorine-18-fluorodeoxyglucose positron emission tomography in the postchemotherapy management of patients with seminoma: systematic review and meta-analysis.
        Biomed Res Int. 2014; 2014: 852681
        • Asai S.
        • Fukumoto T.
        • Tanji N.
        • et al.
        Fluorodeoxyglucose positron emission tomography/computed tomography for diagnosis of upper urinary tract urothelial carcinoma.
        Int J Clin Oncol. 2015; 20: 1042-1047
        • Tanaka H.
        • Yoshida S.
        • Komai Y.
        • et al.
        Clinical value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in upper tract urothelial carcinoma: impact on detection of metastases and patient management.
        Urologia Internationalis. 2016; 96: 65-72