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Advances in PET Diagnostics for Guiding Targeted Cancer Therapy and Studying In Vivo Cancer Biology

  • Update on Technological Innovations for Cancer Detection and Treatment (T Dickherber, Section Editor)
  • Published:
Current Pathobiology Reports

Abstract

Purpose of Review

We present an overview of recent advances in positron emission tomography (PET) diagnostics as applied to the study of cancer, specifically as a tool to study in vivo cancer biology and to direct targeted cancer therapy. The review is directed to translational and clinical cancer investigators who may not be familiar with these applications of PET cancer diagnostics, but whose research might benefit from these advancing tools.

Recent Findings

We highlight recent advances in 3 areas: (1) the translation of PET imaging cancer biomarkers to clinical trials; (2) methods for measuring cancer metabolism in vivo in patients; and (3) advances in PET instrumentation, including total-body PET, that enable new methodologies. We emphasize approaches that have been translated to human studies.

Summary

PET imaging methodology enables unique in vivo cancer diagnostics that go beyond cancer detection and staging, providing an improved ability to guide cancer treatment and an increased understanding of in vivo human cancer biology.

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References

  1. Friedman AA, Letai A, Fisher DE, Flaherty KT. Precision medicine for cancer with next-generation functional diagnostics. Nat Rev Cancer. 2015;15(12):747–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mankoff DA. A definition of molecular imaging. J Nucl Med. 2007;48(6):18N 21N.

    PubMed  Google Scholar 

  3. Farwell MD, Clark AS, Mankoff DA. How imaging biomarkers can inform clinical trials and clinical practice in the era of targeted cancer therapy. JAMA Oncol. 2015;1(4):421–2.

    Article  PubMed  Google Scholar 

  4. Pantel AR, Mankoff DA. Molecular imaging to guide systemic cancer therapy: illustrative examples of PET imaging cancer biomarkers. Cancer Lett. 2017;387:25–31.

    Article  CAS  PubMed  Google Scholar 

  5. Subramaniam RM, Shields AF, Sachedina A, Hanna L, Duan F, Siegel BA, et al. Impact on patient management of [18F]-fluorodeoxyglucose-positron emission tomography (PET) used for cancer diagnosis: analysis of data from the National Oncologic PET Registry. Oncologist. 2016;21(9):1079–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Van Poznak C, Somerfield MR, Bast RC, Cristofanilli M, Goetz MP, Gonzalez-Angulo AM, et al. Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2015;33(24):2695–704.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Chudgar AV, Mankoff DA. Molecular imaging and precision medicine in breast cancer. PET Clin. 2017;12(1):39–51.

    Article  PubMed  Google Scholar 

  8. Mankoff DA, Eary JF, Link JM, Muzi M, Rajendran JG, Spence AM, et al. Tumor-specific positron emission tomography imaging in patients: [18F] fluorodeoxyglucose and beyond. Clin Cancer Res. 2007;13(12):3460–9.

    Article  CAS  PubMed  Google Scholar 

  9. Aboagye EO, Kraeber-Bodere F. Highlights lecture EANM 2016: "Embracing molecular imaging and multi-modal imaging: a smart move for nuclear medicine towards personalized medicine". Eur J Nucl Med Mol Imaging. 2017;44(9):1559–74.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Mankoff DA. Imaging studies in anticancer drug development. In: Hidalo H, Eckhardt SG, Garrett-Meyer E, Clendeninn N, editors. Principles of anticancer drug development. New York: Springer; 2011. p. 275–304.

    Chapter  Google Scholar 

  11. Weber WA. Positron emission tomography as an imaging biomarker. J Clin Oncol. 2006;24(20):3282–92.

    Article  CAS  PubMed  Google Scholar 

  12. Patton JA, Townsend DW, Hutton BF. Hybrid imaging technology: from dreams and vision to clinical devices. Semin Nucl Med. 2009;39(4):247–63.

    Article  PubMed  Google Scholar 

  13. Hartwell L, Mankoff D, Paulovich A, Ramsey S, Swisher E. Cancer biomarkers: a systems approach. Nat Biotechnol. 2006;24(8):905–8.

    Article  CAS  PubMed  Google Scholar 

  14. Henry NL, Hayes DF. Cancer biomarkers. Mol Oncol. 2012;6(2):140–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Schmidt KT, Chau CH, Price DK, Figg WD. Precision oncology medicine: the clinical relevance of patient-specific biomarkers used to optimize cancer treatment. J Clin Pharmacol. 2016;56(12):1484–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jaffee EM, Dang CV, Agus DB, Alexander BM, Anderson KC, Ashworth A, et al. Future cancer research priorities in the USA: a lancet oncology commission. Lancet Oncol. 2017;18(11):e653–706.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Mankoff DA, Farwell MD, Clark AS, Pryma DA. Making molecular imaging a clinical tool for precision oncology: a review. JAMA Oncol. 2017;3(5):695–701.

    Article  PubMed  Google Scholar 

  18. O’Connor JP, Aboagye EO, Adams JE, Aerts HJ, Barrington SF, Beer AJ, et al. Imaging biomarker roadmap for cancer studies. Nat Rev Clin Oncol. 2017;14(3):169–86.

    Article  CAS  PubMed  Google Scholar 

  19. O’Connor JP, Rose CJ, Waterton JC, Carano RA, Parker GJ, Jackson A. Imaging intratumor heterogeneity: role in therapy response, resistance, and clinical outcome. Clin Cancer Res. 2015;21(2):249–57.

    Article  CAS  PubMed  Google Scholar 

  20. Shankar LK. The clinical evaluation of novel imaging methods for cancer management. Nat Rev Clin Oncol. 2012;9(12):738–44.

    Article  CAS  PubMed  Google Scholar 

  21. Moon EJ, Brizel DM, Chi JT, Dewhirst MW. The potential role of intrinsic hypoxia markers as prognostic variables in cancer. Antioxid Redox Signal. 2007;9(8):1237–94.

    Article  CAS  PubMed  Google Scholar 

  22. Rajendran JG, Krohn KA. F-18 fluoromisonidazole for imaging tumor hypoxia: imaging the microenvironment for personalized cancer therapy. Semin Nucl Med. 2015;45(2):151–62.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ling CC, Humm J, Larson S, Amols H, Fuks Z, Leibel S, et al. Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality. Int J Radiat Oncol Biol Phys. 2000;47(3):551–60.

    Article  CAS  PubMed  Google Scholar 

  24. Xu Z, Li XF, Zou H, Sun X, Shen B. (18)F-Fluoromisonidazole in tumor hypoxia imaging. Oncotarget. 2017;8(55):94969–79.

    PubMed  PubMed Central  Google Scholar 

  25. Quartuccio N, Asselin MC. The validation path of hypoxia PET imaging: focus on brain tumours. Curr Med Chem. 2018;25(26):3074–95.

    Article  CAS  PubMed  Google Scholar 

  26. Bekaert L, Valable S, Lechapt-Zalcman E, Ponte K, Collet S, Constans JM, et al. [18F]-FMISO PET study of hypoxia in gliomas before surgery: correlation with molecular markers of hypoxia and angiogenesis. Eur J Nucl Med Mol Imaging. 2017;44(8):1383–92.

    Article  CAS  PubMed  Google Scholar 

  27. Chakhoyan A, Guillamo JS, Collet S, Kauffmann F, Delcroix N, Lechapt-Zalcman E, et al. FMISO-PET-derived brain oxygen tension maps: application to glioblastoma and less aggressive gliomas. Sci Rep. 2017;7(1):10210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Spence AM, Muzi M, Swanson KR, O’Sullivan F, Rockhill JK, Rajendran JG, et al. Regional hypoxia in glioblastoma multiforme quantified with [18F]fluoromisonidazole positron emission tomography before radiotherapy: correlation with time to progression and survival. Clin Cancer Res. 2008;14(9):2623–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gerstner ER, Zhang Z, Fink JR, Muzi M, Hanna L, Greco E, et al. ACRIN 6684: assessment of tumor hypoxia in newly diagnosed glioblastoma using 18F-FMISO PET and MRI. Clin Cancer Res. 2016;22(20):5079–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lonning PE, Haynes BP, Straume AH, Dunbier A, Helle H, Knappskog S, et al. Exploring breast cancer estrogen disposition: the basis for endocrine manipulation. Clin Cancer Res. 2011;17(15):4948–58.

    Article  CAS  PubMed  Google Scholar 

  31. 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.

    Article  CAS  PubMed  Google Scholar 

  32. van Kruchten M, de Vries EGE, Brown M, de Vries EFJ, Glaudemans A, Dierckx R, et al. PET imaging of oestrogen receptors in patients with breast cancer. Lancet Oncol. 2013;14(11):e465–e75.

    Article  CAS  PubMed  Google Scholar 

  33. Chae SY, Ahn SH, Kim SB, Han S, Lee SH, Oh SJ, et al. Diagnostic accuracy and safety of 16alpha-[(18)F]fluoro-17beta-oestradiol PET-CT for the assessment of oestrogen receptor status in recurrent or metastatic lesions in patients with breast cancer: a prospective cohort study. Lancet Oncol. 2019;20(4):546–55.

    Article  CAS  PubMed  Google Scholar 

  34. Mintun MA, Welch MJ, Siegel BA, Mathias CJ, Brodack JW, McGuire AH, et al. Breast cancer: PET imaging of estrogen receptors. Radiology. 1988;169(1):45–8.

    Article  CAS  PubMed  Google Scholar 

  35. 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.

    Article  PubMed  Google Scholar 

  36. Evangelista L, Guarneri V, Conte PF. 18F-Fluoroestradiol positron emission tomography in breast cancer patients: Systematic review of the literature & meta-analysis. Curr Radiopharm. 2016;9(3):244–257.

  37. Fowler AM, Clark AS, Katzenellenbogen JA, Linden HM, Dehdashti F. Imaging diagnostic and therapeutic targets: steroid receptors in breast cancer. J Nucl Med. 2016;57(Suppl 1):75S–80S.

    Article  CAS  PubMed  Google Scholar 

  38. Salem K, Kumar M, Yan Y, Jeffery JJ, Kloepping KC, Michel CJ, et al. Sensitivity and isoform specificity of (18)F-fluorofuranylnorprogesterone for measuring progesterone receptor protein response to estradiol challenge in breast cancer. J Nucl Med 2018.

  39. 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.

    Article  CAS  PubMed  Google Scholar 

  40. 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.

    Article  CAS  PubMed  Google Scholar 

  41. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ulaner GA, Lyashchenko SK, Riedl C, Ruan S, Zanzonico PB, Lake D, et al. First-in-human human epidermal growth factor receptor 2-targeted imaging using (89)Zr-pertuzumab PET/CT: dosimetry and clinical application in patients with breast cancer. J Nucl Med. 2018;59(6):900–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Donabedian PL, Kossatz S, Engelbach JA, Jannetti SA, Carney B, Young RJ, et al. Discriminating radiation injury from recurrent tumor with [(18)F]PARPi and amino acid PET in mouse models. EJNMMI Res. 2018;8(1):59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Edmonds CE, Makvandi M, Lieberman BP, Xu K, Zeng C, Li S, et al. [(18)F]FluorThanatrace uptake as a marker of PARP1 expression and activity in breast cancer. Am J Nucl Med Mol Imaging. 2016;6(1):94–101.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Makvandi M, Pantel A, Schwartz L, Schubert E, Xu K, Hsieh CJ, et al. A PET imaging agent for evaluating PARP-1 expression in ovarian cancer. J Clin Invest. 2018;128(5):2116–26.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Michel LS, Dyroff S, Brooks FJ, Spayd KJ, Lim S, Engle JT, et al. PET of poly (ADP-ribose) polymerase activity in cancer: preclinical assessment and first in-human studies. Radiology. 2017;282(2):453–63.

    Article  PubMed  Google Scholar 

  47. Wilson T, Xavier MA, Knight J, Verhoog S, Torres JB, Mosley M, et al. PET imaging of PARP expression using [(18)F]olaparib. J Nucl Med. 2018.

  48. Fox JJ, Gavane SC, Blanc-Autran E, Nehmeh S, Gonen M, Beattie B, et al. Positron emission tomography/computed tomography-based assessments of androgen receptor expression and glycolytic activity as a prognostic biomarker for metastatic castration-resistant prostate cancer. JAMA Oncol. 2018;4(2):217–24.

    Article  PubMed  Google Scholar 

  49. Bensch F, van der Veen EL, Lub-de Hooge MN, Jorritsma-Smit A, Boellaard R, Kok IC, et al. (89)Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer. Nat Med. 2018;24(12):1852–8.

    Article  CAS  PubMed  Google Scholar 

  50. Tavare R, Escuin-Ordinas H, Mok S, McCracken MN, Zettlitz KA, Salazar FB, et al. An effective immuno-PET imaging method to monitor CD8-dependent responses to immunotherapy. Cancer Res. 2016;76(1):73–82.

    Article  CAS  PubMed  Google Scholar 

  51. Serkova NJ, Eckhardt SG. Metabolic imaging to assess treatment response to cytotoxic and cytostatic agents. Front Oncol. 2016;6:152.

    Article  PubMed  PubMed Central  Google Scholar 

  52. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. 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.

    Article  CAS  PubMed  Google Scholar 

  54. Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, et al. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. J Clin Oncol : official journal of the American Society of Clinical Oncology. 2010;28(30):4594–600.

    Article  CAS  Google Scholar 

  55. Wang Y, Ulaner G, Manning HC, et al. Validation of target engagement using 18F-fluoroestradiol PET in patients undergoing therapy with selective estrogen receptor degrader, ARN-810 (GDC-0810). J Nucl Med. 2015;56:565.

    Article  CAS  Google Scholar 

  56. Connolly RM, Leal JP, Goetz MP, Zhang Z, Zhou XC, Jacobs LK, et al. TBCRC 008: early change in 18F-FDG uptake on PET predicts response to preoperative systemic therapy in human epidermal growth factor receptor 2-negative primary operable breast cancer. J Nucl Med. 2015;56(1):31–7.

    Article  PubMed  Google Scholar 

  57. Gebhart G, Gamez C, Holmes E, Robles J, Garcia C, Cortes M, et al. 18F-FDG PET/CT for early prediction of response to neoadjuvant lapatinib, trastuzumab, and their combination in HER2-positive breast cancer: results from Neo-ALTTO. J Nucl Med. 2013;54(11):1862–8.

    Article  CAS  PubMed  Google Scholar 

  58. 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.

    Article  CAS  PubMed  Google Scholar 

  59. 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.

    Article  CAS  PubMed  Google Scholar 

  60. 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.

    Article  CAS  PubMed  Google Scholar 

  61. Elmi A, McDonald ES, Mankoff D. Imaging tumor proliferation in breast cancer: current update on predictive imaging biomarkers. PET Clin. 2018;13(3):445–57.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Bading JR, Shields AF. Imaging of cell proliferation: status and prospects. J Nucl Med. 2008;49(Suppl 2):64S–80S.

    Article  CAS  PubMed  Google Scholar 

  63. Contractor KB, Kenny LM, Stebbing J, Rosso L, Ahmad R, Jacob J, et al. [18F]-3'Deoxy-3'-fluorothymidine positron emission tomography and breast cancer response to docetaxel. Clin Cancer Res. 2011;17(24):7664–72.

    Article  CAS  PubMed  Google Scholar 

  64. Crippa F, Agresti R, Sandri M, Mariani G, Padovano B, Alessi A, et al. (1)(8)F-FLT PET/CT as an imaging tool for early prediction of pathological response in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy: a pilot study. Eur J Nucl Med Mol Imaging. 2015;42(6):818–30.

    Article  CAS  PubMed  Google Scholar 

  65. Kenny L, Coombes RC, Vigushin DM, Al-Nahhas A, Shousha S, Aboagye EO. Imaging early changes in proliferation at 1 week post chemotherapy: a pilot study in breast cancer patients with 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography. Eur J Nucl Med Mol Imaging. 2007;34(9):1339–47.

    Article  PubMed  Google Scholar 

  66. Raccagni I, Belloli S, Valtorta S, Stefano A, Presotto L, Pascali C, et al. [18F]FDG and [18F]FLT PET for the evaluation of response to neo-adjuvant chemotherapy in a model of triple negative breast cancer. PLoS One. 2018;13(5):e0197754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kostakoglu L, Duan F, Idowu MO, Jolles PR, Bear HD, Muzi M, et al. A phase II study of 3′-deoxy-3'-18F-fluorothymidine PET in the assessment of early response of breast cancer to neoadjuvant chemotherapy: results from ACRIN 6688. J Nucl Med. 2015;56(11):1681–9.

    Article  CAS  PubMed  Google Scholar 

  68. Dehdashti F, Laforest R, Gao F, Shoghi KI, Aft RL, Nussenbaum B, et al. Assessment of cellular proliferation in tumors by PET using 18F-ISO-1. J Nucl Med. 2013;54(3):350–7.

    Article  CAS  PubMed  Google Scholar 

  69. Elmi A, Makvandi M, Weng CC, Hou C, Clark AS, Mach RH, et al. Cell-proliferation imaging for monitoring response to CDK4/6 inhibition combined with endocrine-therapy in breast cancer: comparison of [(18)F]FLT and [(18)F]ISO-1 PET/CT. Clin Cancer Res. 2019;25:3063–73.

    Article  CAS  PubMed  Google Scholar 

  70. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.

    Article  CAS  PubMed  Google Scholar 

  71. Moghbel MC, Kostakoglu L, Zukotynski K, Chen DL, Nadel H, Niederkohr R, et al. Response assessment criteria and their applications in lymphoma: part 1. J Nucl Med. 2016;57(6):928–35.

    Article  CAS  PubMed  Google Scholar 

  72. Cook GJ, Azad GK, Goh V. Imaging bone metastases in breast cancer: staging and response assessment. J Nucl Med. 2016;57(Suppl 1):27S–33S.

    Article  CAS  PubMed  Google Scholar 

  73. Specht JM, Tam SL, Kurland BF, Gralow JR, Livingston RB, Linden HM, et al. Serial 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) to monitor treatment of bone-dominant metastatic breast cancer predicts time to progression (TTP). Breast Cancer Res Treat. 2007;105(1):87–94.

    Article  PubMed  Google Scholar 

  74. Tateishi U, Gamez C, Dawood S, Yeung HW, Cristofanilli M, Macapinlac HA. Bone metastases in patients with metastatic breast cancer: morphologic and metabolic monitoring of response to systemic therapy with integrated PET/CT. Radiology. 2008;247(1):189–96.

    Article  PubMed  Google Scholar 

  75. Peterson LM, O’Sullivan J, Wu QV, Novakova-Jiresova A, Jenkins I, Lee JH, et al. Prospective study of serial (18)F-FDG PET and (18)F-fluoride PET to predict time to skeletal-related events, time to progression, and survival in patients with bone-dominant metastatic breast cancer. J Nucl Med. 2018;59(12):1823–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl 1):122S–50S.

    Article  CAS  PubMed  Google Scholar 

  77. Pinker K, Riedl C, Weber WA. Evaluating tumor response with FDG PET: updates on PERCIST, comparison with EORTC criteria and clues to future developments. Eur J Nucl Med Mol Imaging. 2017;44(Suppl 1):55–66.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Eckelman WC, Mankoff DA. Choosing a single target as a biomarker or therapeutic using radioactive probes. Nucl Med Biol. 2015;42(5):421–5.

    Article  CAS  PubMed  Google Scholar 

  79. Warburg O, Posener K, Negelein E. Ueber den stoffwechsel der tumoren. Biochem Z. 1924;152(1):319–44.

    Google Scholar 

  80. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  CAS  PubMed  Google Scholar 

  81. Liberti MV, Locasale JW. The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci. 2016;41(3):211–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Huang SC. Anatomy of SUV. Standardized uptake value. Nucl Med Biol. 2000;27(7):643–6.

    Article  CAS  PubMed  Google Scholar 

  83. Lammertsma AA. Forward to the past: the case for quantitative PET imaging. J Nucl Med. 2017;58(7):1019–24.

    Article  CAS  PubMed  Google Scholar 

  84. Pantel AR, Ackerman D, Lee SC, Mankoff DA, Gade TP. Imaging cancer metabolism: underlying biology and emerging strategies. J Nucl Med. 2018;59(9):1340–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 2008;7(1):11–20.

    Article  CAS  PubMed  Google Scholar 

  86. Schug ZT, Vande Voorde J, Gottlieb E. The metabolic fate of acetate in cancer. Nat Rev Cancer. 2016;16(11):708–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Buxton DB, Schwaiger M, Nguyen A, Phelps ME, Schelbert HR. Radiolabeled acetate as a tracer of myocardial tricarboxylic acid cycle flux. Circ Res. 1988;63(3):628–34.

    Article  CAS  PubMed  Google Scholar 

  88. Brown M, Marshall DR, Sobel BE, Bergmann SR. Delineation of myocardial oxygen utilization with carbon-11-labeled acetate. Circulation. 1987;76(3):687–96.

    Article  CAS  PubMed  Google Scholar 

  89. Plathow C, Weber WA. Tumor cell metabolism imaging. J Nucl Med. 2008;49(Suppl 2):43S–63S.

    Article  CAS  PubMed  Google Scholar 

  90. Flavin R, Peluso S, Nguyen PL, Loda M. Fatty acid synthase as a potential therapeutic target in cancer. Future Oncol. 2010;6(4):551–62.

    Article  CAS  PubMed  Google Scholar 

  91. Huo L, Guo J, Dang Y, Lv J, Zheng Y, Li F, et al. Kinetic analysis of dynamic (11)C-acetate PET/CT imaging as a potential method for differentiation of hepatocellular carcinoma and benign liver lesions. Theranostics. 2015;5(4):371–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Grassi I, Nanni C, Allegri V, Morigi JJ, Montini GC, Castellucci P, et al. The clinical use of PET with (11)C-acetate. Am J Nucl Med Mol Imaging. 2012;2(1):33–47.

    CAS  PubMed  Google Scholar 

  93. Yu EY, Muzi M, Hackenbracht JA, Rezvani BB, Link JM, Montgomery RB, et al. C-11-acetate and F-18 FDG PET for men with prostate cancer bone metastases: relative findings and response to therapy. Clin Nucl Med. 2011;36(3):192–8.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Altman BJ, Stine ZE, Dang CV. From Krebs to clinic: glutamine metabolism to cancer therapy. Nat Rev Cancer. 2016;16(10):619–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. DeBerardinis RJ, Cheng T. Q’s next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene. 2010;29(3):313–24.

    Article  CAS  PubMed  Google Scholar 

  96. Hosios AM, Hecht VC, Danai LV, Johnson MO, Rathmell JC, Steinhauser ML, et al. Amino acids rather than glucose account for the majority of cell mass in proliferating mammalian cells. Dev Cell. 2016;36(5):540–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Qu W, Oya S, Lieberman BP, Ploessl K, Wang L, Wise DR, et al. Preparation and characterization of L-[5-11C]-glutamine for metabolic imaging of tumors. J Nucl Med. 2012;53(1):98–105.

    Article  CAS  PubMed  Google Scholar 

  98. Qu W, Zha Z, Ploessl K, Lieberman BP, Zhu L, Wise DR, et al. Synthesis of optically pure 4-fluoro-glutamines as potential metabolic imaging agents for tumors. J Am Chem Soc. 2011;133(4):1122–33.

    Article  CAS  PubMed  Google Scholar 

  99. Lieberman BP, Ploessl K, Wang L, Qu W, Zha Z, Wise DR, et al. PET imaging of glutaminolysis in tumors by 18F-(2S,4R)4-fluoroglutamine. J Nucl Med. 2011;52(12):1947–55.

  100. Venneti S, Dunphy MP, Zhang H, Pitter KL, Zanzonico P, Campos C, et al. Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo. Sci Transl Med. 2015;7(274):274ra17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Dunphy MPS, Harding JJ, Venneti S, Zhang H, Burnazi EM, Bromberg J, et al. In vivo PET assay of tumor glutamine flux and metabolism: in-human trial of (18)F-(2S,4R)-4-fluoroglutamine. Radiology. 2018;287(2):667–75.

    Article  PubMed  Google Scholar 

  102. Zhou R, Pantel AR, Li S, Lieberman BP, Ploessl K, Choi H, et al. [(18)F](2S,4R)4-Fluoroglutamine PET detects glutamine pool size changes in triple-negative breast cancer in response to glutaminase inhibition. Cancer Res. 2017;77(6):1476–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Pantel AR, Lee H, Li S, Doot RK, Mach RH, Mankoff DA, et al. Abstract 2851: cellular glutamine pool size change in response to glutaminase inhibition detected by kinetic analysis of [<sup>18</sup>F](2S,4R)4-fluoroglutamine. J Nucl Med. 2017;77(13 Supplement):2851.

    Google Scholar 

  104. Schulte ML, Fu A, Zhao P, Li J, Geng L, Smith ST, et al. Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models. Nat Med. 2018;24(2):194–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Kalinsky K, Harding J, DeMichele A, Infante J, Gogineni K, Owonikoko T, et al. Abstract PD3-13: phase 1 study of CB-839, a first-in-class oral inhibitor of glutaminase, in combination with paclitaxel in patients with advanced triple negative breast cancer. Cancer Res. 2018;78(4 Supplement):PD3–13.

    Google Scholar 

  106. Surti S, Karp JS. Advances in time-of-flight PET. Phys Med. 2016;32(1):12–22.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Surti S, Kuhn A, Werner ME, Perkins AE, Kolthammer J, Karp JS. Performance of Philips Gemini TF PET/CT scanner with special consideration for its time-of-flight imaging capabilities. J Nucl Med. 2007;48(3):471–80.

    PubMed  Google Scholar 

  108. Karp JS, Surti S, Daube-Witherspoon ME, Muehllehner G. Benefit of time-of-flight in PET: experimental and clinical results. J Nucl Med. 2008;49(3):462–70.

    Article  PubMed  Google Scholar 

  109. Kadrmas DJ, Casey ME, Conti M, Jakoby BW, Lois C, Townsend DW. Impact of time-of-flight on PET tumor detection. J Nucl Med. 2009;50(8):1315–23.

    Article  PubMed  Google Scholar 

  110. Lois C, Jakoby BW, Long MJ, Hubner KF, Barker DW, Casey ME, et al. An assessment of the impact of incorporating time-of-flight information into clinical PET/CT imaging. J Nucl Med. 2010;51(2):237–45.

    Article  PubMed  Google Scholar 

  111. Surti S, Scheuermann J, El Fakhri G, Daube-Witherspoon ME, Lim R, Abi-Hatem N, et al. Impact of time-of-flight PET on whole-body oncologic studies: a human observer lesion detection and localization study. J Nucl Med. 2011;52(5):712–9.

    Article  PubMed  Google Scholar 

  112. Vandenberghe S, Mikhaylova E, D'Hoe E, Mollet P, Karp JS. Recent developments in time-of-flight PET. EJNMMI Phys. 2016;3(1):3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Hsu DFC, Ilan E, Peterson WT, Uribe J, Lubberink M, Levin CS. Studies of a next-generation silicon-photomultiplier-based time-of-flight PET/CT system. J Nucl Med. 2017;58(9):1511–8.

    Article  CAS  PubMed  Google Scholar 

  114. Reddin JS, Scheuermann JS, Bharkhada D, Smith AM, Casey ME, Conti M, et al. Performance evaluation of the SiPM-based Siemens Biograph Vision PET/CT System. Conference record of the 2018 IEEE Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC), vol. 2018. Sydney: AU.

  115. Cherry SR, Jones T, Karp JS, Qi J, Moses WW, Badawi RD, et al. Maximizing sensitivity to create new opportunities for clinical research and patient care. J Nucl Med. 2018;59(1):3–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Surti S, Karp JS. Impact of detector design on imaging performance of a long axial field-of-view, whole-body PET scanner. Phys Med Biol. 2015;60(13):5343–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Viswanath V, Daube-Witherspoon ME, Schmall JP, Surti S, Werner ME, Muehllehner G, et al. Development of PET for total-body imaging. Acta Phys Pol B. 2017;48(10):1555–66.

    Article  Google Scholar 

  118. Karp JS, Vishwanath V, Geagan M, Muehllehner G, Pantel A, Parma M, et al. PennPET Explorer: Design and preliminary performance of a whole-body imager. J Nucl Med. 2019.

  119. Badawi RD, Shi H, Hu P, Chen S, Xu T, Price PM, et al. First in human imaging studies with the explorer total-body PET scanner. J Nucl Med. 2019;60:299–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Krohn KA, O’Sullivan F, Crowley J, Eary JF, Linden HM, Link JM, et al. Challenges in clinical studies with multiple imaging probes. Nucl Med Biol. 2007;34(7):879–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

Work presented in this review is partially supported by the following grants: NIH R33-CA-225310, NIH R01-CA211337, Susan G Komen SAC130060, NIH R01-CA113941, NIH R01-CA206187, NIH R01CA-225874, NIH P30-CA016520, and NIH KL2-TR001879.

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Correspondence to David A. Mankoff.

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Austin R. Pantel, Varsha Viswanath, and Joel S. Karp declare no conflict of interest. David A. Mankoff discloses that his spouse was the CEO of Trevarx at the time this manuscript was published.

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Mankoff, D.A., Pantel, A.R., Viswanath, V. et al. Advances in PET Diagnostics for Guiding Targeted Cancer Therapy and Studying In Vivo Cancer Biology. Curr Pathobiol Rep 7, 97–108 (2019). https://doi.org/10.1007/s40139-019-00202-9

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