Molecular Imaging and Biology

, Volume 20, Issue 4, pp 501–509 | Cite as

Prostate Cancer Theranostics Targeting Gastrin-Releasing Peptide Receptors

  • Lucia Baratto
  • Hossein JadvarEmail author
  • Andrei Iagaru
Review Article


Gastrin-releasing peptide receptors (GRPRs), part of the bombesin (BBN) family, are aberrantly overexpressed in many cancers, including those of the breast, prostate, pancreas, and lung, and therefore present an attractive target for cancer diagnosis and therapy. Different bombesin analogs have been radiolabeled and used for imaging diagnosis, staging, evaluation of biochemical recurrence, and assessment of metastatic disease in patients with prostate cancer. Recently, interest has shifted from BBN-like receptor agonists to antagonists, because the latter does not induce adverse effects and demonstrate superior in vivo pharmacokinetics. We review the preclinical and clinical literatures on the use of GRPRs as targets for imaging and therapy of prostate cancer, with a focus on the newer developments and theranostic potential of GRPR peptides.

Key words

Bombesin GRPR Prostate PET Theranostics 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Attard G, Parker C, Eeles RA, Schröder F, Tomlins SA, Tannock I, Drake CG, de Bono JS (2016) Prostate cancer. Lancet 387(10013):70–82. CrossRefPubMedGoogle Scholar
  2. 2.
    Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66(1):7–30. CrossRefPubMedGoogle Scholar
  3. 3.
    Han M, Partin AW, Zahurak M, Piantadosi S, Epstein JI, Walsh PC (2003) Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol 169(2):517–523. CrossRefPubMedGoogle Scholar
  4. 4.
    Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, Mason M, Matveev V, Wiegel T, Zattoni F, Mottet N, European Association of Urology (2014) EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol 65(1):124–137. CrossRefPubMedGoogle Scholar
  5. 5.
    Hovels AM, Heesakkers RA, Adang EM et al (2008) The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin Radiol 63(4):387–395. CrossRefPubMedGoogle Scholar
  6. 6.
    Jensen RT, Battey JF, Spindel ER, Benya RV (2008) International Union of Pharmacology. LXVIII. Mammalian bombesin receptors: nomenclature, distribution, pharmacology, signaling, and functions in normal and disease states. Pharmacol Rev 60(1):1–42. CrossRefPubMedGoogle Scholar
  7. 7.
    Mansi R, Fleischmann A, Macke HR, Reubi JC (2013) Targeting GRPR in urological cancers—from basic research to clinical application. Nat Rev Urol 10(4):235–244. CrossRefPubMedGoogle Scholar
  8. 8.
    Smith CJ, Volkert WA, Hoffman TJ (2003) Gastrin releasing peptide (GRP) receptor targeted radiopharmaceuticals: a concise update. Nucl Med Biol 30(8):861–868. CrossRefPubMedGoogle Scholar
  9. 9.
    Smith CJ, Volkert WA, Hoffman TJ (2005) Radiolabeled peptide conjugates for targeting of the bombesin receptor superfamily subtypes. Nucl Med Biol 32(7):733–740. CrossRefPubMedGoogle Scholar
  10. 10.
    Ferreira CA, Fuscaldi LL, Townsend DM, Rubello D, Barros ALB (2017) Radiolabeled bombesin derivatives for preclinical oncological imaging. Biomed Pharmacother 87:58–72. CrossRefPubMedGoogle Scholar
  11. 11.
    Lee LF, Guan J, Qiu Y, Kung HJ (2001) Neuropeptide-induced androgen independence in prostate cancer cells: roles of nonreceptor tyrosine kinases Etk/Bmx, Src, and focal adhesion kinase. Mol Cell Biol 21(24):8385–8397. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ischia J, Patel O, Bolton D, Shulkes A, Baldwin GS (2014) Expression and function of gastrin-releasing peptide (GRP) in normal and cancerous urological tissues. BJU Int 113(Suppl 2):40–47. CrossRefPubMedGoogle Scholar
  13. 13.
    Desai SJ, Ma AH, Tepper CG, Chen HW, Kung HJ (2006) Inappropriate activation of the androgen receptor by nonsteroids: involvement of the Src kinase pathway and its therapeutic implications. Cancer Res 66(21):10449–10459. CrossRefPubMedGoogle Scholar
  14. 14.
    Patel O, Dumesny C, Shulkes A, Baldwin GS (2007) C-terminal fragments of the gastrin-releasing peptide precursor stimulate cell proliferation via a novel receptor. Endocrinology 148(3):1330–1339. CrossRefPubMedGoogle Scholar
  15. 15.
    Shimoda J (1992) Effects of bombesin and its antibody on growth of human prostatic carcinoma cell lines. Nihon Hinyokika Gakkai Zasshi 83(9):1459–1468PubMedGoogle Scholar
  16. 16.
    Bologna M, Festuccia C, Muzi P, Biordi L, Ciomei M (1989) Bombesin stimulates growth of human prostatic cancer cells in vitro. Cancer 63(9):1714–1720CrossRefPubMedGoogle Scholar
  17. 17.
    Hoosein NM, Logothetis CJ, Chung LW (1993) Differential effects of peptide hormones bombesin, vasoactive intestinal polypeptide and somatostatin analog RC-160 on the invasive capacity of human prostatic carcinoma cells. J Urol 149(5):1209–1213. CrossRefPubMedGoogle Scholar
  18. 18.
    Aprikian AG, Tremblay L, Han K, Chevalier S (1997) Bombesin stimulates the motility of human prostate-carcinoma cells through tyrosine phosphorylation of focal adhesion kinase and of integrin-associated proteins. Int J Cancer 72(3):498–504.<498::AID-IJC19>3.0.CO;2-8 CrossRefPubMedGoogle Scholar
  19. 19.
    Sun B, Halmos G, Schally AV, Wang X, Martinez M (2000) Presence of receptors for bombesin/gastrin-releasing peptide and mRNA for three receptor subtypes in human prostate cancers. Prostate 42(4):295–303.<295::AID-PROS7>3.0.CO;2-B CrossRefPubMedGoogle Scholar
  20. 20.
    Markwalder R, Reubi JC (1999) Gastrin-releasing peptide receptors in the human prostate: relation to neoplastic transformation. Cancer Res 59(5):1152–1159PubMedGoogle Scholar
  21. 21.
    Weber HC (2009) Regulation and signaling of human bombesin receptors and their biological effects. Curr Opin Endocrinol Diabetes Obes 16(1):66–71. CrossRefPubMedGoogle Scholar
  22. 22.
    Bartholdi MF, Wu JM, Pu H, Troncoso P, Eden PA, Feldman RI (1998) In situ hybridization for gastrin-releasing peptide receptor (GRP receptor) expression in prostatic carcinoma. Int J Cancer 79(1):82–90.<82::AID-IJC16>3.0.CO;2-J CrossRefPubMedGoogle Scholar
  23. 23.
    Nagasaki S, Nakamura Y, Maekawa T et al (2012) Immunohistochemical analysis of gastrin-releasing peptide receptor (GRPR) and possible regulation by estrogen receptor betacx in human prostate carcinoma. Neoplasma 59(02):224–232. CrossRefPubMedGoogle Scholar
  24. 24.
    Beer M, Montani M, Gerhardt J, Wild PJ, Hany TF, Hermanns T, Müntener M, Kristiansen G (2012) Profiling gastrin-releasing peptide receptor in prostate tissues: clinical implications and molecular correlates. Prostate 72(3):318–325. CrossRefPubMedGoogle Scholar
  25. 25.
    Fleischmann A, Waser B, Reubi JC (2009) High expression of gastrin-releasing peptide receptors in the vascular bed of urinary tract cancers: promising candidates for vascular targeting applications. Endocr Relat Cancer 16(2):623–633. CrossRefPubMedGoogle Scholar
  26. 26.
    Ananias HJ, van den Heuvel MC, Helfrich W, de Jong IJ (2009) Expression of the gastrin-releasing peptide receptor, the prostate stem cell antigen and the prostate-specific membrane antigen in lymph node and bone metastases of prostate cancer. Prostate 69(10):1101–1108. CrossRefPubMedGoogle Scholar
  27. 27.
    Constantinides C, Lazaris AC, Haritopoulos KN, Pantazopoulos D, Chrisofos M, Giannopoulos A (2003) Immunohistochemical detection of gastrin releasing peptide in patients with prostate cancer. World J Urol 21(3):183–187. CrossRefPubMedGoogle Scholar
  28. 28.
    Dijkgraaf I, Franssen GM, McBride WJ, D'Souza CA, Laverman P, Smith CJ, Goldenberg DM, Oyen WJG, Boerman OC (2012) PET of tumors expressing gastrin-releasing peptide receptor with an 18F-labeled bombesin analog. J Nucl Med 53(6):947–952. CrossRefPubMedGoogle Scholar
  29. 29.
    Zhang H, Chen J, Waldherr C, Hinni K, Waser B, Reubi JC, Maecke HR (2004) Synthesis and evaluation of bombesin derivatives on the basis of pan-bombesin peptides labeled with indium-111, lutetium-177, and yttrium-90 for targeting bombesin receptor-expressing tumors. Cancer Res 64(18):6707–6715. CrossRefPubMedGoogle Scholar
  30. 30.
    Garcia Garayoa E, Schweinsberg C, Maes V et al (2007) New [99mTc]bombesin analogues with improved biodistribution for targeting gastrin releasing-peptide receptor-positive tumors. Q J Nucl Med Mol Imaging 51(1):42–50PubMedGoogle Scholar
  31. 31.
    Abiraj K, Mansi R, Tamma ML, Fani M, Forrer F, Nicolas G, Cescato R, Reubi JC, Maecke HR (2011) Bombesin antagonist-based radioligands for translational nuclear imaging of gastrin-releasing peptide receptor-positive tumors. J Nucl Med 52(12):1970–1978. CrossRefPubMedGoogle Scholar
  32. 32.
    Dapp S, Garcia Garayoa E, Maes V et al (2011) PEGylation of (99m)Tc-labeled bombesin analogues improves their pharmacokinetic properties. Nucl Med Biol 38(7):997–1009. CrossRefPubMedGoogle Scholar
  33. 33.
    Chatalic KL, Franssen GM, van Weerden WM et al (2014) Preclinical comparison of Al18F- and 68Ga-labeled gastrin-releasing peptide receptor antagonists for PET imaging of prostate cancer. J Nucl Med 55(12):2050–2056. CrossRefPubMedGoogle Scholar
  34. 34.
    Biddlecombe GB, Rogers BE, de Visser M, Parry JJ, de Jong M, Erion JL, Lewis JS (2007) Molecular imaging of gastrin-releasing peptide receptor-positive tumors in mice using 64Cu- and 86Y–DOTA-(Pro1,Tyr4)-bombesin(1–14). Bioconjug Chem 18(3):724–730. CrossRefPubMedGoogle Scholar
  35. 35.
    Dapp S, Muller C, Garayoa EG et al (2012) PEGylation, increasing specific activity and multiple dosing as strategies to improve the risk-benefit profile of targeted radionuclide therapy with 177Lu-DOTA-bombesin analogues. EJNMMI Res 2(1):24. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Wild D, Frischknecht M, Zhang H, Morgenstern A, Bruchertseifer F, Boisclair J, Provencher-Bolliger A, Reubi JC, Maecke HR (2011) Alpha- versus beta-particle radiopeptide therapy in a human prostate cancer model (213Bi-DOTA-PESIN and 213Bi-AMBA versus 177Lu-DOTA-PESIN). Cancer Res 71(3):1009–1018. CrossRefPubMedGoogle Scholar
  37. 37.
    Maina T, Nock B, Mather S (2006) Targeting prostate cancer with radiolabelled bombesins. Cancer Imaging 6(1):153–157. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Yu Z, Ananias HJ, Carlucci G et al (2013) An update of radiolabeled bombesin analogs for gastrin-releasing peptide receptor targeting. Curr Pharm Des 19(18):3329–3341. CrossRefPubMedGoogle Scholar
  39. 39.
    Maddalena ME, Fox J, Chen J, Feng W, Cagnolini A, Linder KE, Tweedle MF, Nunn AD, Lantry LE (2009) 177Lu-AMBA biodistribution, radiotherapeutic efficacy, imaging, and autoradiography in prostate cancer models with low GRP-R expression. J Nucl Med 50(12):2017–2024. CrossRefPubMedGoogle Scholar
  40. 40.
    Nock BA, Nikolopoulou A, Galanis A, Cordopatis P, Waser B, Reubi JC, Maina T (2005) Potent bombesin-like peptides for GRP-receptor targeting of tumors with 99mTc: a preclinical study. J Med Chem 48(1):100–110. CrossRefPubMedGoogle Scholar
  41. 41.
    Zhang H, Schuhmacher J, Waser B, Wild D, Eisenhut M, Reubi JC, Maecke HR (2007) DOTA-PESIN, a DOTA-conjugated bombesin derivative designed for the imaging and targeted radionuclide treatment of bombesin receptor-positive tumours. Eur J Nucl Med Mol Imaging 34(8):1198–1208. CrossRefPubMedGoogle Scholar
  42. 42.
    Baum R, Prasad V, Mutloka N, Frischknecht M, Maecke H, Reubi J (2007) Molecular imaging of bombesin receptors in various tumors by Ga-68 AMBA PET/CT: first results. J Nucl Med 48:79PGoogle Scholar
  43. 43.
    Mansi R, Wang X, Forrer F, Kneifel S, Tamma ML, Waser B, Cescato R, Reubi JC, Maecke HR (2009) Evaluation of a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated bombesin-based radioantagonist for the labeling with single-photon emission computed tomography, positron emission tomography, and therapeutic radionuclides. Clin Cancer Res 15(16):5240–5249. CrossRefPubMedGoogle Scholar
  44. 44.
    Carlucci G, Kuipers A, Ananias HJ et al (2015) GRPR-selective PET imaging of prostate cancer using [(18)F]-lanthionine-bombesin analogs. Peptides 67:45–54. CrossRefPubMedGoogle Scholar
  45. 45.
    Lane SR, Nanda P, Rold TL, Sieckman GL, Figueroa SD, Hoffman TJ, Jurisson SS, Smith CJ (2010) Optimization, biological evaluation and microPET imaging of copper-64-labeled bombesin agonists, [64Cu-NO2A-(X)-BBN(7-14)NH2], in a prostate tumor xenografted mouse model. Nucl Med Biol 37(7):751–761. CrossRefPubMedGoogle Scholar
  46. 46.
    Shokeen M, Anderson CJ (2009) Molecular imaging of cancer with copper-64 radiopharmaceuticals and positron emission tomography (PET). Acc Chem Res 42(7):832–841. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Garrison JC, Rold TL, Sieckman GL, Figueroa SD, Volkert WA, Jurisson SS, Hoffman TJ (2007) In vivo evaluation and small-animal PET/CT of a prostate cancer mouse model using 64Cu bombesin analogs: side-by-side comparison of the CB-TE2A and DOTA chelation systems. J Nucl Med 48(8):1327–1337. CrossRefPubMedGoogle Scholar
  48. 48.
    Van de Wiele C, Dumont F, Vanden Broecke R, Oosterlinck W, Cocquyt V, Serreyn R, Peers S, Thornback J, Slegers G, Dierckx RA (2000) Technetium-99m RP527, a GRP analogue for visualisation of GRP receptor-expressing malignancies: a feasibility study. Eur J Nucl Med 27(11):1694–1699. CrossRefPubMedGoogle Scholar
  49. 49.
    Scopinaro F, De Vincentis G, Varvarigou AD, Laurenti C, Iori F, Remediani S, Chiarini S, Stella S (2003) 99mTc-bombesin detects prostate cancer and invasion of pelvic lymph nodes. Eur J Nucl Med Mol Imaging 30(10):1378–1382. CrossRefPubMedGoogle Scholar
  50. 50.
    Maina TNB, Kulkarni H, Singh A, Baum RP (2017) Theranostic prospects of gastrin-releasing peptide receptor-radioantagonists in oncology. PET Clin 12(3):297–309. CrossRefPubMedGoogle Scholar
  51. 51.
    Ginj M, Zhang H, Waser B, Cescato R, Wild D, Wang X, Erchegyi J, Rivier J, Macke HR, Reubi JC (2006) Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors. Proc Natl Acad Sci U S A 103(44):16436–16441. CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Sonni I, Baratto L, Iagaru A (2017) Imaging of prostate cancer using gallium-68-labeled bombesin. PET Clin 12(2):159–171. CrossRefPubMedGoogle Scholar
  53. 53.
    Mansi R, Wang X, Forrer F, Waser B, Cescato R, Graham K, Borkowski S, Reubi JC, Maecke HR (2011) Development of a potent DOTA-conjugated bombesin antagonist for targeting GRPr-positive tumours. Eur J Nucl Med Mol Imaging 38(1):97–107. CrossRefPubMedGoogle Scholar
  54. 54.
    Gourni E, Mansi R, Jamous M, Waser B, Smerling C, Burian A, Buchegger F, Reubi JC, Maecke HR (2014) N-terminal modifications improve the receptor affinity and pharmacokinetics of radiolabeled peptidic gastrin-releasing peptide receptor antagonists: examples of 68Ga- and 64Cu-labeled peptides for PET imaging. J Nucl Med 55(10):1719–1725. CrossRefPubMedGoogle Scholar
  55. 55.
    Dalm SU, Bakker IL, de Blois E, Doeswijk GN, Konijnenberg MW, Orlandi F, Barbato D, Tedesco M, Maina T, Nock BA, de Jong M (2017) 68Ga/177Lu-NeoBOMB1, a novel radiolabeled GRPR antagonist for theranostic use in oncology. J Nucl Med 58(2):293–299. CrossRefPubMedGoogle Scholar
  56. 56.
    Nock BA, Kaloudi A, Lymperis E, Giarika A, Kulkarni HR, Klette I, Singh A, Krenning EP, de Jong M, Maina T, Baum RP (2017) Theranostic perspectives in prostate cancer with the gastrin-releasing peptide receptor antagonist NeoBOMB1: preclinical and first clinical results. J Nucl Med 58(1):75–80. CrossRefPubMedGoogle Scholar
  57. 57.
    Yang M, Gao H, Zhou Y, Ma Y, Quan Q, Lang L, Chen K, Niu G, Yan Y, Chen X (2011) F-labeled GRPR agonists and antagonists: a comparative study in prostate cancer imaging. Theranostics 1:220–229. CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Pan D, Yan Y, Yang R, Xu YP, Chen F, Wang L, Luo S, Yang M (2014) PET imaging of prostate tumors with 18F-Al-NOTA-MATBBN. Contrast Media Mol Imaging 9(5):342–348. CrossRefPubMedGoogle Scholar
  59. 59.
    Pan D, Xu YP, Yang RH et al (2014) A new (68)Ga-labeled BBN peptide with a hydrophilic linker for GRPR-targeted tumor imaging. Amino Acids 46(6):1481–1489. CrossRefPubMedGoogle Scholar
  60. 60.
    Gourni E, Del Pozzo L, Kheirallah E, Smerling C, Waser B, Reubi JC, Paterson BM, Donnelly PS, Meyer PT, Maecke HR (2015) Copper-64 labeled macrobicyclic sarcophagine coupled to a GRP receptor antagonist shows great promise for PET imaging of prostate cancer. Mol Pharm 12(8):2781–2790. CrossRefPubMedGoogle Scholar
  61. 61.
    Roivainen A, Kahkonen E, Luoto P, Borkowski S, Hofmann B, Jambor I, Lehtio K, Rantala T, Rottmann A, Sipila H, Sparks R, Suilamo S, Tolvanen T, Valencia R, Minn H (2013) Plasma pharmacokinetics, whole-body distribution, metabolism, and radiation dosimetry of 68Ga bombesin antagonist BAY 86-7548 in healthy men. J Nucl Med 54(6):867–872. CrossRefPubMedGoogle Scholar
  62. 62.
    Kahkonen E, Jambor I, Kemppainen J, Lehtio K, Gronroos TJ, Kuisma A, Luoto P, Sipila HJ, Tolvanen T, Alanen K, Silen J, Kallajoki M, Roivainen A, Schafer N, Schibli R, Dragic M, Johayem A, Valencia R, Borkowski S, Minn H (2013) In vivo imaging of prostate cancer using [68Ga]-labeled bombesin analog BAY86-7548. Clin Cancer Res 19(19):5434–5443. CrossRefPubMedGoogle Scholar
  63. 63.
    Zhang J, Niu G, Lang L, Li F, Fan X, Yan X, Yao S, Yan W, Huo L, Chen L, Li Z, Zhu Z, Chen X (2017) Clinical translation of a dual integrin alphavbeta3- and gastrin-releasing peptide receptor-targeting PET radiotracer, 68Ga-BBN-RGD. J Nucl Med 58(2):228–234. CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Li ZB, Wu Z, Chen K, Ryu EK, Chen X (2008) 18F-labeled BBN-RGD heterodimer for prostate cancer imaging. J Nucl Med 49(3):453–461. CrossRefPubMedGoogle Scholar
  65. 65.
    Iagaru AH (2017) Dual integrin αvβ3- and gastrin-releasing peptide receptor-targeting PET radiotracer (68Ga-BBN-RGD). J Nucl MedGoogle Scholar
  66. 66.
    Wieser G, Mansi R, Grosu AL, Schultze-Seemann W, Dumont-Walter RA, Meyer PT, Maecke HR, Reubi JC, Weber WA (2014) Positron emission tomography (PET) imaging of prostate cancer with a gastrin releasing peptide receptor antagonist—from mice to men. Theranostics 4(4):412–419. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Ananias HJ, Yu Z, Hoving HD et al (2013) Application of (99m)Technetium-HYNIC(tricine/TPPTS)-Aca-Bombesin(7-14) SPECT/CT in prostate cancer patients: a first-in-man study. Nucl Med Biol 40:933–938Google Scholar
  68. 68.
    Mather SJ, Nock BA, Maina T et al (2014) GRP receptor imaging of prostate cancer using [(99m)Tc]Demobesin 4: a first-in-man study. Mol Imaging Biol 16:888–895Google Scholar
  69. 69.
    Wieser G, Popp I, Christian Rischke H et al (2017) Diagnosis of recurrent prostate cancer with PET/CT imaging using the gastrin-releasing peptide receptor antagonist 68Ga-RM2: Preliminary results in patients with negative or inconclusive [18F]Fluoroethylcholine-PET/CT. Eur J Nucl Med Mol Imaging 44:1463–1472Google Scholar
  70. 70.
    Minamimoto R, Hancock S, Schneider B et al (2016) Pilot Comparison of (6)(8)Ga-RM2 PET and (6)(8)Ga-PSMA-11 PET in Patients with Biochemically Recurrent Prostate Cancer. J Nucl Med 57:557–562Google Scholar
  71. 71.
    Maina T, Bergsma H, Kulkarni HR et al (2016) Preclinical and first clinical experience with the gastrin-releasing peptide receptor-antagonist [(6)(8)Ga]SB3 and PET/CT. Eur J Nucl Med Mol Imaging 43:964–973Google Scholar
  72. 72.
    Minamimoto R, Sonni I, Hancock S et al (2017) Prospective evaluation of 68Ga-RM2 PET/MRI in patients with biochemical recurrence of prostate cancer and negative conventional imaging. J Nucl Med.

Copyright information

© World Molecular Imaging Society 2017

Authors and Affiliations

  1. 1.Department of RadiologyStanford UniversityStanfordUSA
  2. 2.Department of RadiologyUniversity of Southern CaliforniaLos AngelesUSA

Personalised recommendations