Advertisement

The AAPS Journal

, 20:43 | Cite as

Receptor Occupancy Imaging Studies in Oncology Drug Development

  • Ingrid J. G. Burvenich
  • Sagun Parakh
  • Adam C. Parslow
  • Sze Ting Lee
  • Hui K. Gan
  • Andrew M. Scott
Review Article Theme: Advances and Applications of In Vivo Medical Imaging in Drug Development and Regulation
Part of the following topical collections:
  1. Theme: Advances and Applications of In Vivo Medical Imaging in Drug Development and Regulation

Abstract

The selection of therapeutic dose for the most effective treatment of tumours is an intricate interplay of factors. Molecular imaging with positron emission tomography (PET) or single–photon emission computed tomography (SPECT) can address questions central to this selection: Does the drug reach its target? Does the drug engage with the target of interest? Is the drug dose sufficient to elicit the desired pharmacological effect? Does the dose saturate available target sites? Combining functional PET and SPECT imaging with anatomical imaging technologies such as magnetic resonance imaging (MRI) or computed tomography (CT) allows drug occupancy at the target to be related directly to anatomical or physiological changes in a tissue resulting from therapy. In vivo competition studies, using a tracer amount of radioligand that binds to the tumour receptor with high specificity, enable direct assessment of the relationship between drug plasma concentration and target occupancy. Including imaging studies in early drug development can aid with dose selection and suggest improvements for patient stratification to obtain higher effective utility from a drug after approval. In this review, the potential value of including translational receptor occupancy studies and molecular imaging strategies early on in drug development is addressed.

KEY WORDS

drug development positron emission tomography (PET) receptor imaging receptor occupancy single–photon emission tomography (SPECT) 

References

  1. 1.
    de Vries EG, de Jong S, Gietema JA. Molecular imaging as a tool for drug development and trial design. J Clin Oncol. 2015;33(24):2585–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Gurfinkel M, Ke S, Wang W, Li C, Sevick-Muraca EM. Quantifying molecular specificity of alphavbeta3 integrin-targeted optical contrast agents with dynamic optical imaging. J Biomed Opt. 2005;10(3):034019.PubMedCrossRefGoogle Scholar
  3. 3.
    Ardeshirpour Y, Chernomordik V, Hassan M, Zielinski R, Capala J, Gandjbakhche A. In vivo fluorescence lifetime imaging for monitoring the efficacy of the cancer treatment. Clin Cancer Res. 2014;20(13):3531–9.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Tichauer KM, Samkoe KS, Sexton KJ, Hextrum SK, Yang HH, Klubben WS, et al. In vivo quantification of tumor receptor binding potential with dual-reporter molecular imaging. Mol Imaging Biol. 2012;14(5):584–92.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Venema CM, Mammatas LH, Schroder CP, van Kruchten M, Apollonio G, Glaudemans A, et al. Androgen and estrogen receptor imaging in metastatic breast cancer patients as a surrogate for tissue biopsies. J Nucl Med. 2017;58(12):1906–12.PubMedCrossRefGoogle Scholar
  6. 6.
    Gambhir SS. Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer. 2002;2(9):683–93.PubMedCrossRefGoogle Scholar
  7. 7.
    Khalil MM, Tremoleda JL, Bayomy TB, Gsell W. Molecular SPECT imaging: an overview. Int J Mol Imaging. 2011;2011:796025.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev. 2003;17(5):545–80.PubMedCrossRefGoogle Scholar
  9. 9.
    Mlynarik V. Introduction to nuclear magnetic resonance. Anal Biochem. 2017;529:4–9.PubMedCrossRefGoogle Scholar
  10. 10.
    O'Donoghue JA, Smith-Jones PM, Humm JL, Ruan S, Pryma DA, Jungbluth AA, et al. 124I-huA33 antibody uptake is driven by A33 antigen concentration in tissues from colorectal cancer patients imaged by immuno-PET. J Nucl Med. 2011;52(12):1878–85.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Carrasquillo JA, Pandit-Taskar N, O'Donoghue JA, Humm JL, Zanzonico P, Smith-Jones PM, et al. (124)I-huA33 antibody PET of colorectal cancer. J Nucl Med. 2011;52(8):1173–80.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Larson SM, Morris M, Gunther I, Beattie B, Humm JL, Akhurst TA, et al. Tumor localization of 16beta-18F-fluoro-5alpha-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer. J Nucl Med. 2004;45(3):366–73.PubMedGoogle Scholar
  13. 13.
    Vargas HA, Wassberg C, Fox JJ, Wibmer A, Goldman DA, Kuk D, 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(1):220–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Zhang J, Niu G, Lang L, Li F, Fan X, Yan X, et al. Clinical translation of a dual integrin alphavbeta3- and gastrin-releasing peptide receptor-targeting PET radiotracer, 68Ga-BBN-RGD. J Nucl Med. 2017;58(2):228–34.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Liu Z, Yan Y, Liu S, Wang F, Chen X. (18)F, (64)Cu, and (68)Ga labeled RGD-bombesin heterodimeric peptides for PET imaging of breast cancer. Bioconjug Chem. 2009;20(5):1016–25.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Liu Z, Niu G, Wang F, Chen X. (68)Ga-labeled NOTA-RGD-BBN peptide for dual integrin and GRPR-targeted tumor imaging. Eur J Nucl Med Mol Imaging. 2009;36(9):1483–94.PubMedCrossRefGoogle Scholar
  17. 17.
    Knetsch PA, Petrik M, Griessinger CM, Rangger C, Fani M, Kesenheimer C, et al. [68Ga]NODAGA-RGD for imaging alphavbeta3 integrin expression. Eur J Nucl Med Mol Imaging. 2011;38(7):1303–12.PubMedCrossRefGoogle Scholar
  18. 18.
    Mirfeizi L, Walsh J, Kolb H, Campbell-Verduyn L, Dierckx RA, Feringa BL, et al. Synthesis of [18F]RGD-K5 by catalyzed [3 + 2] cycloaddition for imaging integrin alphavbeta3 expression in vivo. Nucl Med Biol. 2013;40(5):710–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Chen SH, Wang HM, Lin CY, Chang JT, Hsieh CH, Liao CT, et al. RGD-K5 PET/CT in patients with advanced head and neck cancer treated with concurrent chemoradiotherapy: results from a pilot study. Eur J Nucl Med Mol Imaging. 2016;43(9):1621–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Li D, Zhao X, Zhang L, Li F, Ji N, Gao Z, et al. (68)Ga-PRGD2 PET/CT in the evaluation of glioma: a prospective study. Mol Pharm. 2014;11(11):3923–9.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Zheng K, Liang N, Zhang J, Lang L, Zhang W, Li S, et al. 68Ga-NOTA-PRGD2 PET/CT for integrin imaging in patients with lung cancer. J Nucl Med. 2015;56(12):1823–7.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Guo N, Lang L, Li W, Kiesewetter DO, Gao H, Niu G, et al. Quantitative analysis and comparison study of [18F]AlF-NOTA-PRGD2, [18F]FPPRGD2 and [68Ga]Ga-NOTA-PRGD2 using a reference tissue model. PLoS One. 2012;7(5):e37506.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Gao S, Wu H, Li W, Zhao S, Teng X, Lu H, et al. A pilot study imaging integrin alphavbeta3 with RGD PET/CT in suspected lung cancer patients. Eur J Nucl Med Mol Imaging. 2015;42(13):2029–37.PubMedCrossRefGoogle Scholar
  24. 24.
    Zhang H, Liu N, Gao S, Hu X, Zhao W, Tao R, et al. Can an (1)(8)F-ALF-NOTA-PRGD2 PET/CT scan predict treatment sensitivity to concurrent Chemoradiotherapy in patients with newly diagnosed glioblastoma? J Nucl Med. 2016;57(4):524–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Minamimoto R, Jamali M, Barkhodari A, Mosci C, Mittra E, Shen B, et al. Biodistribution of the (1)(8)F-FPPRGD(2) PET radiopharmaceutical in cancer patients: an atlas of SUV measurements. Eur J Nucl Med Mol Imaging. 2015;42(12):1850–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Ilovich O, Natarajan A, Hori S, Sathirachinda A, Kimura R, Srinivasan A, et al. Development and validation of an Immuno-PET tracer as a companion diagnostic agent for antibody-drug conjugate therapy to target the CA6 epitope. Radiology. 2015;276(1):191–8.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Hekman M, Rijpkema M, Oosterwijk E, Langenhuijsen H, Boerman O, Oyen W, et al. Intraoperative dual-modality imaging in clear cell renal cell carcinoma using Indium-111-DOTA-girentuximab-IRDye800CW [abstract]. Eur Urol Suppl. 2017;16(3):e1831.CrossRefGoogle Scholar
  28. 28.
    Hekman MC, Boerman OC, de Weijert M, Bos DL, Oosterwijk E, Langenhuijsen JF, et al. Targeted dual-modality imaging in renal cell carcinoma: an ex vivo kidney perfusion study. Clin Cancer Res. 2016;22(18):4634–42.PubMedCrossRefGoogle Scholar
  29. 29.
    Divgi CR, Pandit-Taskar N, Jungbluth AA, Reuter VE, Gonen M, Ruan S, 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(4):304–10.PubMedCrossRefGoogle Scholar
  30. 30.
    Pawlak D, Rangger C, Kolenc Peitl P, Garnuszek P, Maurin M, Ihli L, et al. From preclinical development to clinical application: kit formulation for radiolabelling the minigastrin analogue CP04 with In-111 for a first-in-human clinical trial. Eur J Pharm Sci. 2016;85:1–9.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Rossi EA, Goldenberg DM, Cardillo TM, McBride WJ, Sharkey RM, Chang CH. Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targeting. Proc Natl Acad Sci U S A. 2006;103(18):6841–6.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Bodet-Milin C, Faivre-Chauvet A, Carlier T, Rauscher A, Bourgeois M, Cerato E, et al. Immuno-PET using anticarcinoembryonic antigen bispecific antibody and 68Ga-labeled peptide in metastatic medullary thyroid carcinoma: clinical optimization of the pretargeting parameters in a first-in-human trial. J Nucl Med. 2016;57(10):1505–11.PubMedCrossRefGoogle Scholar
  33. 33.
    Schoffelen R, Boerman OC, Goldenberg DM, Sharkey RM, van Herpen CM, Franssen GM, et al. Development of an imaging-guided CEA-pretargeted radionuclide treatment of advanced colorectal cancer: first clinical results. Br J Cancer. 2013;109(4):934–42.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Meller B, Rave-Franck M, Breunig C, Schirmer M, Baehre M, Nadrowitz R, et al. Novel carcinoembryonic-antigen-(CEA)-specific pretargeting system to assess tumor cell viability after irradiation of colorectal cancer cells. Strahlenther Onkol. 2011;187(2):120–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Reilly EB, Phillips AC, Buchanan FG, Kingsbury G, Zhang Y, Meulbroek JA, et al. Characterization of ABT-806, a humanized tumor-specific anti-EGFR monoclonal antibody. Mol Cancer Ther. 2015;14(5):1141–51.PubMedCrossRefGoogle Scholar
  36. 36.
    Scott AM, Lee FT, Tebbutt N, Herbertson R, Gill SS, Liu Z, et al. A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors. Proc Natl Acad Sci U S A. 2007;104(10):4071–6.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Genne P, Berthet C, Raguin O, Chalon S, Tizon X, Serriere S, et al. Preclinical proof of concept for the first Nanocyclix TKI-PET radiotracer targeting activated EGFR positive lung tumors [abstract]. Cancer Res. 2017;77(13 Suppl):1875A.CrossRefGoogle Scholar
  38. 38.
    Xiao Z, Song Y, Kai W, Sun X, Shen B. Evaluation of 99mTc-HYNIC-MPG as a novel SPECT radiotracer to detect EGFR-activating mutations in NSCLC. Oncotarget. 2017;8(25):40732–40.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Xiao Z, Song Y, Wang K, Sun X, Shen B. One-step radiosynthesis of 18F-IRS: a novel radiotracer targeting mutant EGFR in NSCLC for PET/CT imaging. Bioorg Med Chem Lett. 2016;26(24):5985–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Song Y, Xiao Z, Wang K, Wang X, Zhang C, Fang F, et al. Development and evaluation of 18F-IRS for molecular imaging mutant EGF receptors in NSCLC. Sci Rep. 2017;7(1):3121.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Lindenberg L, Adler S, Turkbey IB, Mertan F, Ton A, Do K, et al. Dosimetry and first human experience with 89Zr-panitumumab. Am J Nucl Med Mol Imaging. 2017;7(4):195–203.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Chang AJ, De Silva RA, Development LSE. Characterization of 89Zr-labeled panitumumab for immuno-positron emission tomographic imaging of the epidermal growth factor receptor. Mol Imaging. 2013;12(1):17–27.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Menke-van der Houven van Oordt CW, Gootjes EC, Huisman MC, Vugts DJ, Roth C, Luik AM, et al. 89Zr-cetuximab PET imaging in patients with advanced colorectal cancer. Oncotarget. 2015;6(30):30384–93.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Su X, Cheng K, Jeon J, Shen B, Venturin GT, Hu X, et al. Comparison of two site-specifically (18)F-labeled affibodies for PET imaging of EGFR positive tumors. Mol Pharm. 2014;11(11):3947–56.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Wang Y, Ayres K, Goldman DA, Dickler MN, Bardia A, Mayer IA, et al. 18F-fluoroestradiol PET/CT measurement of estrogen receptor suppression during a phase I trial of the novel estrogen receptor-targeted therapeutic GDC-0810. Clin Cancer Res. 2017;23(12):3053–60.PubMedCrossRefGoogle Scholar
  46. 46.
    Liao GJ, Clark AS, Schubert EK, Mankoff DA. 18F-Fluoroestradiol PET: current status and potential future clinical applications. J Nucl Med. 2016;57(8):1269–75.PubMedCrossRefGoogle Scholar
  47. 47.
    Venema C, de Vries E, Glaudemans A, Poppema B, Hospers G, Schroder C. 18F-FES PET has added value in staging and therapy decision making in patients with disseminated lobular breast cancer. Clin Nucl Med. 2017;42(8):612–4.PubMedGoogle Scholar
  48. 48.
    Paquette M, Ouellet R, Archambault M, Croteau E, Lecomte R, Benard F. [18F]-fluoroestradiol quantitative PET imaging to differentiate ER+ and ERalpha-knockdown breast tumors in mice. Nucl Med Biol. 2012;39(1):57–64.PubMedCrossRefGoogle Scholar
  49. 49.
    Burvenich IJ, Parakh S, Gan HK, Lee FT, Guo N, Rigopoulos A, et al. Molecular imaging and quantitation of EphA2 expression in xenograft models with 89Zr-DS-8895a. J Nucl Med. 2016;57(6):974–80.PubMedCrossRefGoogle Scholar
  50. 50.
    Wieser G, Popp I, Christian Rischke H, Drendel V, Grosu AL, Bartholoma M, et al. 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. 2017;44(9):1463–72.PubMedCrossRefGoogle Scholar
  51. 51.
    Minamimoto R, Hancock S, Schneider B, Chin FT, Jamali M, Loening A, et al. 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. 2016;57(4):557–62.PubMedCrossRefGoogle Scholar
  52. 52.
    Zhang J, Li D, Lang L, Zhu Z, Wang L, Wu P, et al. 68Ga-NOTA-Aca-BBN(7-14) PET/CT in healthy volunteers and glioma patients. J Nucl Med. 2016;57(1):9–14.PubMedCrossRefGoogle Scholar
  53. 53.
    Gebhart G, Lamberts LE, Wimana Z, Garcia C, Emonts P, Ameye L, et al. Molecular imaging as a tool to investigate heterogeneity of advanced HER2-positive breast cancer and to predict patient outcome under trastuzumab emtansine (T-DM1): the ZEPHIR trial. Ann Oncol. 2016;27(4):619–24.PubMedCrossRefGoogle Scholar
  54. 54.
    Laforest R, Lapi SE, Oyama R, Bose R, Tabchy A, Marquez-Nostra BV, et al. [89Zr]Trastuzumab: evaluation of radiation dosimetry, safety, and optimal imaging parameters in women with HER2-positive breast cancer. Mol Imaging Biol. 2016;18(6):952–9.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    O'Donoghue JA, Lewis JS, Pandit-Taskar N, Fleming SE, Schoder H, Larson SM, et al. Pharmacokinetics, biodistribution, and radiation dosimetry for 89Zr-trastuzumab in patients with esophagogastric cancer. J Nucl Med. 2018;59(1):161–6.PubMedCrossRefGoogle Scholar
  56. 56.
    Ulaner GA, Hyman DM, Ross DS, Corben A, Chandarlapaty S, Goldfarb S, et al. Detection of HER2-positive metastases in patients with HER2-negative primary breast cancer using 89Zr-trastuzumab PET/CT. J Nucl Med. 2016;57(10):1523–8.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Ulaner GA, Hyman DM, Lyashchenko SK, Lewis JS, Carrasquillo JA. 89Zr-Trastuzumab PET/CT for detection of human epidermal growth factor receptor 2-positive metastases in patients with human epidermal growth factor receptor 2-negative primary breast cancer. Clin Nucl Med. 2017;42(12):912–7.PubMedCrossRefGoogle Scholar
  58. 58.
    Mortimer JE, Bading JR, Park JM, Frankel PH, Carroll MI, Tran TT, et al. Tumor uptake of 64Cu-DOTA-trastuzumab in patients with metastatic breast cancer. J Nucl Med. 2018;59(1):38–43.PubMedCrossRefGoogle Scholar
  59. 59.
    Mortimer JE, Bading JR, Colcher DM, Conti PS, Frankel PH, Carroll MI, et al. Functional imaging of human epidermal growth factor receptor 2-positive metastatic breast cancer using (64)Cu-DOTA-trastuzumab PET. J Nucl Med. 2014;55(1):23–9.PubMedCrossRefGoogle Scholar
  60. 60.
    D'Huyvetter M, De Vos J, Xavier C, Pruszynski M, Sterckx YGJ, Massa S, et al. 131I-labeled anti-HER2 Camelid sdAb as a theranostic tool in cancer treatment. Clin Cancer Res. 2017;23(21):6616–28.PubMedCrossRefGoogle Scholar
  61. 61.
    Marquez BV, Ikotun OF, Zheleznyak A, Wright B, Hari-Raj A, Pierce RA, et al. Evaluation of (89)Zr-pertuzumab in breast cancer xenografts. Mol Pharm. 2014;11(11):3988–95.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    England CG, Ehlerding EB, Hernandez R, Rekoske BT, Graves SA, Sun H, et al. Preclinical pharmacokinetics and biodistribution studies of 89Zr-labeled pembrolizumab. J Nucl Med. 2017;58(1):162–8.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Niemeijer A-LN, Smit EF, GaMSv D, Windhorst AD, Huisman MC, Hendrikse NH, et al. Whole body PD-1 and PD-L1 PET with 89Zr-nivolumab and 18F- BMS-986192 in pts with NSCLC. J Clin Oncol. 2017;35(15_suppl):e20047-e.Google Scholar
  64. 64.
    Eiber M, Weirich G, Holzapfel K, Souvatzoglou M, Haller B, Rauscher I, et al. Simultaneous 68Ga-PSMA HBED-CC PET/MRI improves the localization of primary prostate cancer. Eur Urol. 2016;70(5):829–36.PubMedCrossRefGoogle Scholar
  65. 65.
    Afshar-Oromieh A, Haberkorn U, Schlemmer HP, Fenchel M, Eder M, Eisenhut M, et al. Comparison of PET/CT and PET/MRI hybrid systems using a 68Ga-labelled PSMA ligand for the diagnosis of recurrent prostate cancer: initial experience. Eur J Nucl Med Mol Imaging. 2014;41(5):887–97.PubMedCrossRefGoogle Scholar
  66. 66.
    Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, et al. Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging. 2017;44(8):1258–68.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, 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. J Urol. 2016;195(5):1436–43.PubMedCrossRefGoogle Scholar
  68. 68.
    Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of hybrid (6)(8)Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56(5):668–74.PubMedCrossRefGoogle Scholar
  69. 69.
    Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, et al. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42(2):197–209.PubMedCrossRefGoogle Scholar
  70. 70.
    Eder M, Neels O, Muller M, Bauder-Wust U, Remde Y, Schafer M, et al. Novel preclinical and radiopharmaceutical aspects of [68Ga]Ga-PSMA-HBED-CC: a new PET tracer for imaging of prostate cancer. Pharmaceuticals (Basel). 2014;7(7):779–96.CrossRefGoogle Scholar
  71. 71.
    Szabo Z, Mena E, Rowe SP, Plyku D, Nidal R, Eisenberger MA, et al. Initial evaluation of [(18)F]DCFPyL for prostate-specific membrane antigen (PSMA)-targeted PET imaging of prostate cancer. Mol Imaging Biol. 2015;17(4):565–74.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Gorin MA, Rowe SP, Patel HD, Vidal I, Mana-Ay M, Javadi MS, et al. Prostate specific membrane antigen targeted 18F-DCFPyL positron emission tomography/computerized tomography in the preoperative staging of men with high risk prostate cancer: results of a prospective, phase II, single center study. J Urol. 2018;199(1):126–32.PubMedCrossRefGoogle Scholar
  73. 73.
    Rowe SP, Gorin MA, Pomper MG. Imaging of prostate-specific membrane antigen using [18F]DCFPyL. PET Clin. 2017;12(3):289–96.PubMedCrossRefGoogle Scholar
  74. 74.
    Chen Y, Pullambhatla M, Foss CA, Byun Y, Nimmagadda S, Senthamizhchelvan S, et al. 2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pen tanedioic acid, [18F]DCFPyL, a PSMA-based PET imaging agent for prostate cancer. Clin Cancer Res. 2011;17(24):7645–53.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Rowe SP, Gorin MA, Hammers HJ, Som Javadi M, Hawasli H, Szabo Z, et al. Imaging of metastatic clear cell renal cell carcinoma with PSMA-targeted 18F-DCFPyL PET/CT. Ann Nucl Med. 2015;29(10):877–82.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Turkbey B, Mena E, Lindenberg L, Adler S, Bednarova S, Berman R, et al. 18F-DCFBC prostate-specific membrane antigen-targeted PET/CT imaging in localized prostate cancer: correlation with multiparametric MRI and histopathology. Clin Nucl Med. 2017;42(10):735–40.PubMedCrossRefGoogle Scholar
  77. 77.
    Mena E, Lindenberg ML, Shih JH, Adler S, Harmon S, Bergvall E, et al. Clinical impact of PSMA-based 18F-DCFBC PET/CT imaging in patients with biochemically recurrent prostate cancer after primary local therapy. Eur J Nucl Med Mol Imaging. 2017;Google Scholar
  78. 78.
    Cho SY, Gage KL, Mease RC, Senthamizhchelvan S, Holt DP, Jeffrey-Kwanisai A, et al. Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer. J Nucl Med. 2012;53(12):1883–91.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Pandit-Taskar N, O'Donoghue JA, Durack JC, Lyashchenko SK, Cheal SM, Beylergil V, et al. A phase I/II study for analytic validation of 89Zr-J591 ImmunoPET as a molecular imaging agent for metastatic prostate cancer. Clin Cancer Res. 2015;21(23):5277–85.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Fung EK, Cheal SM, Fareedy SB, Punzalan B, Beylergil V, Amir J, et al. Targeting of radiolabeled J591 antibody to PSMA-expressing tumors: optimization of imaging and therapy based on non-linear compartmental modeling. EJNMMI Res. 2016;6(1):7.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Kroiss A, Putzer D, Decristoforo C, Uprimny C, Warwitz B, Nilica B, et al. 68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT. Eur J Nucl Med Mol Imaging. 2013;40(4):514–23.PubMedCrossRefGoogle Scholar
  82. 82.
    Kunikowska J, Krolicki L, Pawlak D, Zerizer I, Mikolajczak R. Semiquantitative analysis and characterization of physiological biodistribution of (68)Ga-DOTA-TATE PET/CT. Clin Nucl Med. 2012;37(11):1052–7.PubMedCrossRefGoogle Scholar
  83. 83.
    Prasad V, Baum RP. Biodistribution of the Ga-68 labeled somatostatin analogue DOTA-NOC in patients with neuroendocrine tumors: characterization of uptake in normal organs and tumor lesions. Q J Nucl Med Mol Imaging. 2010;54(1):61–7.PubMedGoogle Scholar
  84. 84.
    Naswa N, Sharma P, Kumar A, Nazar AH, Kumar R, Chumber S, et al. Gallium-68-DOTA-NOC PET/CT of patients with gastroenteropancreatic neuroendocrine tumors: a prospective single-center study. AJR Am J Roentgenol. 2011;197(5):1221–8.PubMedCrossRefGoogle Scholar
  85. 85.
    Naswa N, Sharma P, Nazar AH, Agarwal KK, Kumar R, Ammini AC, et al. Prospective evaluation of 68Ga-DOTA-NOC PET-CT in phaeochromocytoma and paraganglioma: preliminary results from a single centre study. Eur Radiol. 2012;22(3):710–9.PubMedCrossRefGoogle Scholar
  86. 86.
    Henry KE, Ulaner GA, Lewis JS. Human epidermal growth factor receptor 2-targeted PET/single- photon emission computed tomography imaging of breast cancer: noninvasive measurement of a biomarker integral to tumor treatment and prognosis. PET Clin. 2017;12(3):269–88.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Behr TM, Behe M, Trastuzumab WB. Breast cancer. N Engl J Med. 2001;345(13):995–6.PubMedCrossRefGoogle Scholar
  88. 88.
    Dijkers EC, Oude Munnink TH, Kosterink JG, Brouwers AH, Jager PL, de Jong JR, et al. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther. 2010;87(5):586–92.PubMedCrossRefGoogle Scholar
  89. 89.
    Paik S, Kim C, Wolmark N. HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med. 2008;358(13):1409–11.PubMedCrossRefGoogle Scholar
  90. 90.
    Blankenberg FG, Katsikis PD, Tait JF, Davis RE, Naumovski L, Ohtsuki K, et al. In vivo detection and imaging of phosphatidylserine expression during programmed cell death. Proc Natl Acad Sci U S A. 1998;95(11):6349–54.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Takei T, Kuge Y, Zhao S, Sato M, Strauss HW, Blankenberg FG, et al. Time course of apoptotic tumor response after a single dose of chemotherapy: comparison with 99mTc-annexin V uptake and histologic findings in an experimental model. J Nucl Med. 2004;45(12):2083–7.PubMedGoogle Scholar
  92. 92.
    Belhocine T, Steinmetz N, Hustinx R, Bartsch P, Jerusalem G, Seidel L, et al. Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis. Clin Cancer Res. 2002;8(9):2766–74.PubMedGoogle Scholar
  93. 93.
    Yang TJ, Haimovitz-Friedman A, Verheij M. Anticancer therapy and apoptosis imaging. Exp Oncol. 2012;34(3):269–76.PubMedGoogle Scholar
  94. 94.
    Reddy S, Shaller CC, Doss M, Shchaveleva I, Marks JD, Yu JQ, et al. Evaluation of the anti-HER2 C6.5 diabody as a PET radiotracer to monitor HER2 status and predict response to trastuzumab treatment. Clin Cancer Res. 2011;17(6):1509–20.PubMedCrossRefGoogle Scholar
  95. 95.
    Wright GL Jr, Grob BM, Haley C, Grossman K, Newhall K, Petrylak D, et al. Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology. 1996;48(2):326–34.PubMedCrossRefGoogle Scholar
  96. 96.
    Evans MJ, Smith-Jones PM, Wongvipat J, Navarro V, Kim S, Bander NH, et al. Noninvasive measurement of androgen receptor signaling with a positron-emitting radiopharmaceutical that targets prostate-specific membrane antigen. Proc Natl Acad Sci U S A. 2011;108(23):9578–82.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Pool M, Kol A, de Jong S, de Vries EGE, Lub-de Hooge MN, Terwisscha van Scheltinga AGT. 89Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment. MAbs. 2017:1–9.Google Scholar
  98. 98.
    Scott AM, Wiseman G, Welt S, Adjei A, Lee FT, Hopkins W, et al. A phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer. Clin Cancer Res. 2003;9(5):1639–47.PubMedGoogle Scholar
  99. 99.
    Herbertson RA, Tebbutt NC, Lee FT, MacFarlane DJ, Chappell B, Micallef N, et al. Phase I biodistribution and pharmacokinetic study of Lewis Y-targeting immunoconjugate CMD-193 in patients with advanced epithelial cancers. Clin Cancer Res. 2009;15(21):6709–15.PubMedCrossRefGoogle Scholar
  100. 100.
    Dewaraja YK, Schipper MJ, Roberson PL, Wilderman SJ, Amro H, Regan DD, et al. 131I-tositumomab radioimmunotherapy: initial tumor dose-response results using 3-dimensional dosimetry including radiobiologic modeling. J Nucl Med. 2010;51(7):1155–62.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Zanzonico P, Carrasquillo JA, Pandit-Taskar N, O'Donoghue JA, Humm JL, Smith-Jones P, et al. PET-based compartmental modeling of (124)I-A33 antibody: quantitative characterization of patient-specific tumor targeting in colorectal cancer. Eur J Nucl Med Mol Imaging. 2015;42(11):1700–6.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Al-Ahmadie HA, Alden D, Qin LX, Olgac S, Fine SW, Gopalan A, et al. Carbonic anhydrase IX expression in clear cell renal cell carcinoma: an immunohistochemical study comparing 2 antibodies. Am J Surg Pathol. 2008;32(3):377–82.PubMedCrossRefGoogle Scholar
  103. 103.
    Divgi CR, Uzzo RG, Gatsonis C, Bartz R, Treutner S, Yu JQ, et al. Positron emission tomography/computed tomography identification of clear cell renal cell carcinoma: results from the REDECT trial. J Clin Oncol. 2013;31(2):187–94.PubMedCrossRefGoogle Scholar
  104. 104.
    Tomblyn M. Radioimmunotherapy for B-cell non-hodgkin lymphomas. Cancer Control. 2012;19(3):196–203.PubMedCrossRefGoogle Scholar
  105. 105.
    Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125–35.PubMedCrossRefGoogle Scholar
  106. 106.
    Tichauer KM, Wang Y, Pogue BW, Liu JT. Quantitative in vivo cell-surface receptor imaging in oncology: kinetic modeling and paired-agent principles from nuclear medicine and optical imaging. Phys Med Biol. 2015;60(14):R239–69.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Zhang Y, Fox GB. PET imaging for receptor occupancy: meditations on calculation and simplification. J Biomed Res. 2012;26(2):69–76.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Orcutt KD, Adams GP, Wu AM, Silva MD, Harwell C, Hoppin J, et al. Molecular simulation of receptor occupancy and tumor penetration of an antibody and smaller scaffolds: application to molecular imaging. Mol Imaging Biol. 2017;19(5):656–64.PubMedCrossRefGoogle Scholar
  109. 109.
    Mortimer JE, Dehdashti F, Siegel BA, Trinkaus K, Katzenellenbogen JA, Welch MJ. Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol. 2001;19(11):2797–803.PubMedCrossRefGoogle Scholar
  110. 110.
    Peterson LM, Kurland BF, Schubert EK, Link JM, Gadi VK, Specht JM, et al. A phase 2 study of 16α-[18F]-fluoro-17β-estradiol positron emission tomography (FES-PET) as a marker of hormone sensitivity in metastatic breast cancer (MBC). Mol Imaging Biol. 2014;16(3):431–40.PubMedCrossRefGoogle Scholar
  111. 111.
    Dehdashti F, Mortimer JE, Trinkaus K, Naughton MJ, Ellis M, Katzenellenbogen JA, et al. PET-based estradiol challenge as a predictive biomarker of response to endocrine therapy in women with estrogen-receptor-positive breast cancer. Breast Cancer Res Treat. 2009;113(3):509–17.PubMedCrossRefGoogle Scholar
  112. 112.
    Kurland BF, Peterson LM, Lee JH, Schubert EK, Currin ER, Link JM, et al. Estrogen receptor binding (18F-FES PET) and glycolytic activity (18F-FDG PET) predict progression-free survival on endocrine therapy in patients with ER+ breast cancer. Clin Cancer Res. 2017;23(2):407–15.PubMedCrossRefGoogle Scholar
  113. 113.
    Scher HI, Beer TM, Higano CS, Anand A, Taplin M-E, Efstathiou E, et al. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1–2 study. Lancet. 2010;375(9724):1437–46.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Dehdashti F, Picus J, Michalski JM, Dence CS, Siegel BA, Katzenellenbogen JA, et al. Positron tomographic assessment of androgen receptors in prostatic carcinoma. Eur J Nucl Med Mol Imaging. 2005;32(3):344–50.PubMedCrossRefGoogle Scholar
  115. 115.
    Rathkopf DE, Morris MJ, Fox JJ, Danila DC, Slovin SF, Hager JH, et al. Phase I study of ARN-509, a novel antiandrogen, in the treatment of castration-resistant prostate cancer. J Clin Oncol. 2013;31(28):3525–30.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Bonasera TA, O'Neil JP, Xu M, Dobkin JA, Cutler PD, Lich LL, et al. Preclinical evaluation of fluorine-18-labeled androgen receptor ligands in baboons. J Nucl Med. 1996;37(6):1009–15.PubMedGoogle Scholar
  117. 117.
    Vollenweider-Zerargui L, Barrelet L, Wong Y, Lemarchand-Beraud T, Gomez F. The predictive value of estrogen and progesterone receptors’ concentrations on the clinical behavior of breast cancer in women. Clinical correlation on 547 patients. Cancer. 1986;57(6):1171–80.PubMedCrossRefGoogle Scholar
  118. 118.
    Mintun M, Welch M, Siegel B, Mathias C, Brodack J, McGuire A, et al. Breast cancer: PET imaging of estrogen receptors. Radiology. 1988;169(1):45–8.PubMedCrossRefGoogle Scholar
  119. 119.
    Peterson LM, Mankoff DA, Lawton T, Yagle K, Schubert EK, Stekhova S, et al. Quantitative imaging of estrogen receptor expression in breast cancer with PET and 18F-fluoroestradiol. J Nucl Med. 2008;49(3):367–74.PubMedCrossRefGoogle Scholar
  120. 120.
    McGuire AH, Dehdashti F, Siegel BA, Lyss AP, Brodack JW, Mathias CJ, et al. Positron tomographic assessment of 16a-[18F] fluoro-17b-estradiol uptake in metastatic breast carcinoma. J Nucl Med. 1991;32(8):1526–31.PubMedGoogle Scholar
  121. 121.
    Sundararajan L, Linden HM, Link JM, Krohn KA, Mankoff DA. 18F-Fluoroestradiol. Semin Nucl Med. 2007;37(6):470–6.PubMedCrossRefGoogle Scholar
  122. 122.
    Kiesewetter DO, Kilbourn MR, Landvatter SW, Heiman DF, Katzenellenbogen JA, Welch MJ. Preparation of four fluorine-18-labeled estrogens and their selective uptakes in target tissues of immature rats. J Nucl Med. 1984;25(11):1212–21.PubMedGoogle Scholar
  123. 123.
    Pomper MG, VanBrocklin H, Thieme AM, Thomas RD, Kiesewetter DO, Carlson KE, et al. 11 Beta-methoxy-, 11 beta-ethyl- and 17 alpha-ethynyl-substituted 16 alpha-fluoroestradiols: receptor-based imaging agents with enhanced uptake efficiency and selectivity. J Med Chem. 1990;33(12):3143–55.PubMedCrossRefGoogle Scholar
  124. 124.
    Gemignani ML, Patil S, Seshan VE, Sampson M, Humm JL, Lewis JS, et al. Feasibility and predictability of perioperative PET and estrogen receptor ligand in patients with invasive breast cancer. J Nucl Med. 2013;54(10):1697–702.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Heidari P, Deng F, Esfahani SA, Leece AK, Shoup TM, Vasdev N, et al. Pharmacodynamic imaging guides dosing of a selective estrogen receptor degrader. Clin Cancer Res. 2015;21(6):1340–7.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Linden HM, Kurland BF, Peterson LM, Schubert EK, Gralow JR, Specht JM, et al. Fluoroestradiol positron emission tomography reveals differences in pharmacodynamics of aromatase inhibitors, tamoxifen, and fulvestrant in patients with metastatic breast cancer. Clin Cancer Res. 2011;17(14):4799–805.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    van Kruchten M, de Vries EG, Glaudemans AW, van Lanschot MC, van Faassen M, Kema IP, et al. Measuring residual estrogen receptor availability during fulvestrant therapy in patients with metastatic breast cancer. Cancer Discov. 2015;5(1):72–81.PubMedCrossRefGoogle Scholar
  128. 128.
    Linden HM, Stekhova SA, Link JM, Gralow JR, Livingston RB, Ellis GK, et al. Quantitative fluoroestradiol positron emission tomography imaging predicts response to endocrine treatment in breast cancer. J Clin Oncol. 2006;24(18):2793–9.PubMedCrossRefGoogle Scholar
  129. 129.
    Marqus S, Pirogova E, Piva TJ. Evaluation of the use of therapeutic peptides for cancer treatment. J Biomed Sci. 2017;24(1):21.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Heidari P, Wehrenberg-Klee E, Habibollahi P, Yokell D, Kulke M, Mahmood U. Free somatostatin receptor fraction predicts the antiproliferative effect of octreotide in a neuroendocrine tumor model: implications for dose optimization. Cancer Res. 2013;73(23):6865–73.PubMedCrossRefGoogle Scholar
  131. 131.
    Kratochwil C, Stefanova M, Mavriopoulou E, Holland-Letz T, Dimitrakopoulou-Strauss A, Afshar-Oromieh A, et al. SUV of [68Ga]DOTATOC-PET/CT predicts response probability of PRRT in neuroendocrine tumors. Mol Imaging Biol. 2015;17(3):313–8.PubMedCrossRefGoogle Scholar
  132. 132.
    Andrulis IL, Bull SB, Blackstein ME, Sutherland D, Mak C, Sidlofsky S, et al. neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group. J Clin Oncol. 1998;16(4):1340–9.PubMedCrossRefGoogle Scholar
  133. 133.
    Berchuck A, Kamel A, Whitaker R, Kerns B, Olt G, Kinney R, et al. Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res. 1990;50(13):4087–91.PubMedGoogle Scholar
  134. 134.
    Hofmann M, Stoss O, Gaiser T, Kneitz H, Heinmoller P, Gutjahr T, et al. Central HER2 IHC and FISH analysis in a trastuzumab (Herceptin) phase II monotherapy study: assessment of test sensitivity and impact of chromosome 17 polysomy. J Clin Pathol. 2008;61(1):89–94.PubMedCrossRefGoogle Scholar
  135. 135.
    Capala J, Bouchelouche K. Molecular imaging of HER2-positive breast cancer: a step toward an individualized ‘image and treat’ strategy. Curr Opin Oncol. 2010;22(6):559–66.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Tamura K, Kurihara H, Yonemori K, Tsuda H, Suzuki J, Kono Y, et al. 64Cu-DOTA-trastuzumab PET imaging in patients with HER2-positive breast cancer. J Nucl Med. 2013;54(11):1869–75.PubMedCrossRefGoogle Scholar
  137. 137.
    Kurihara H, Hamada A, Yoshida M, Shimma S, Hashimoto J, Yonemori K, et al. (64)Cu-DOTA-trastuzumab PET imaging and HER2 specificity of brain metastases in HER2-positive breast cancer patients. EJNMMI Res. 2015;5:8.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    de Vries EG, Gietema JA, de Jong S. Tumor necrosis factor-related apoptosis-inducing ligand pathway and its therapeutic implications. Clin Cancer Res. 2006;12(8):2390–3.PubMedCrossRefGoogle Scholar
  139. 139.
    Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, et al. TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J. 1997;16(17):5386–97.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Burvenich IJ, Lee FT, Cartwright GA, O'Keefe GJ, Makris D, Cao D, et al. Molecular imaging of death receptor 5 occupancy and saturation kinetics in vivo by humanized monoclonal antibody CS-1008. Clin Cancer Res. 2013;19(21):5984–93.PubMedCrossRefGoogle Scholar
  141. 141.
    Ciprotti M, Tebbutt NC, Lee F-T, Lee S-T, Gan HK, McKee DC, et al. Phase I imaging and pharmacodynamic trial of CS-1008 in patients with metastatic colorectal cancer. J Clin Oncol. 2015;33(24):2609–16.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Gan HK, Burgess AW, Clayton AH, Scott AM. Targeting of a conformationally exposed, tumor-specific epitope of EGFR as a strategy for cancer therapy. Cancer Res. 2012;72(12):2924–30.PubMedCrossRefGoogle Scholar
  143. 143.
    Garrett TP, Burgess AW, Gan HK, Luwor RB, Cartwright G, Walker F, et al. Antibodies specifically targeting a locally misfolded region of tumor associated EGFR. Proc Natl Acad Sci U S A. 2009;106(13):5082–7.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Johns TG, Stockert E, Ritter G, Jungbluth AA, Huang HJS, Cavenee WK, et al. Novel monoclonal antibody specific for the de2-7 epidermal growth factor receptor (EGFR) that also recognizes the EGFR expressed in cells containing amplification of the EGFR gene. Int J Cancer. 2002;98(3):398–408.PubMedCrossRefGoogle Scholar
  145. 145.
    Gan HK, Burge ME, Solomon BJ, Holen KD, Zhang Y, Ciprotti M, et al. A phase I and biodistribution study of ABT-806i, an 111indium-labeled conjugate of the tumor-specific anti-EGFR antibody ABT-806 [abstract]. J Clin Oncol. 2013;31 (suppl; abstr 2520).Google Scholar
  146. 146.
    Azoury SC, Straughan DM, Shukla V. Immune checkpoint inhibitors for cancer therapy: clinical efficacy and safety. Curr Cancer Drug Targets. 2015;15(6):452–62.PubMedCrossRefGoogle Scholar
  147. 147.
    Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14(4):847–56.PubMedCrossRefGoogle Scholar
  148. 148.
    Katz SC, Pillarisetty V, Bamboat ZM, Shia J, Hedvat C, Gonen M, et al. T cell infiltrate predicts long-term survival following resection of colorectal cancer liver metastases. Ann Surg Oncol. 2009;16(9):2524–30.PubMedCrossRefGoogle Scholar
  149. 149.
    Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28(19):3167–75.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Brahmer JR, Tykodi SS, Chow LQ, Hwu W-J, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–65.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Heery CR, O'Sullivan Coyne GH, Marte JL, Singh H, Cordes LM, Madan RA, et al. Pharmacokinetic profile and receptor occupancy of avelumab (MSB0010718C), an anti-PD-L1 monoclonal antibody, in a phase I, open-label, dose escalation trial in patients with advanced solid tumors [abstract]. J Clin Oncol. 2015;33 (suppl; abstr 3055).Google Scholar
  153. 153.
    Agrawal S, Feng Y, Roy A, Kollia G, Lestini B. Nivolumab dose selection: challenges, opportunities, and lessons learned for cancer immunotherapy. J Immunother Cancer. 2016;4(1):72.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Natarajan A, Mayer AT, Xu L, Reeves RE, Gano J, Gambhir SS. Novel radiotracer for immunoPET imaging of PD-1 checkpoint expression on tumor infiltrating lymphocytes. Bioconjug Chem. 2015;26(10):2062–9.PubMedCrossRefGoogle Scholar
  155. 155.
    Hettich M, Braun F, Bartholomä MD, Schirmbeck R, Niedermann G. High-resolution PET imaging with therapeutic antibody-based PD-1/PD-L1 checkpoint tracers. Theranostics. 2016;6(10):1629–40.PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    England CG, Jiang D, Ehlerding EB, Rekoske BT, Ellison PA, Hernandez R, et al. 89Zr-labeled nivolumab for imaging of T-cell infiltration in a humanized murine model of lung cancer. Eur J Nucl Med Mol Imaging. 2018;45(1):110–20.PubMedCrossRefGoogle Scholar
  157. 157.
    Cole EL, Kim J, Donnelly DJ, Smith RA, Cohen D, Lafont V, et al. Radiosynthesis and preclinical PET evaluation of 89Zr-nivolumab (BMS-936558) in healthy non-human primates. Bioorg Med Chem. 2017;25(20):5407–14.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Ingrid J. G. Burvenich
    • 1
    • 2
  • Sagun Parakh
    • 1
    • 2
    • 3
  • Adam C. Parslow
    • 1
    • 2
  • Sze Ting Lee
    • 2
    • 4
  • Hui K. Gan
    • 1
    • 2
    • 3
  • Andrew M. Scott
    • 1
    • 2
    • 3
    • 4
    • 5
    • 6
  1. 1.Tumour Targeting LaboratoryOlivia Newton-John Cancer Research InstituteMelbourneAustralia
  2. 2.School of Cancer MedicineLa Trobe UniversityMelbourneAustralia
  3. 3.Department of Medical OncologyAustin HealthMelbourneAustralia
  4. 4.Department of Molecular Imaging and TherapyAustin HealthMelbourneAustralia
  5. 5.Department of MedicineUniversity of MelbourneMelbourneAustralia
  6. 6.Tumour Targeting LaboratoryOlivia Newton-John Cancer Research InstituteHeidelbergAustralia

Personalised recommendations