Top

European Journal of Nuclear Medicine and Molecular Imaging

Published in:

Open Access 01-08-2019 | Positron Emission Tomography | Review Article

The next era of renal radionuclide imaging: novel PET radiotracers

Authors: Rudolf A. Werner, Xinyu Chen, Constantin Lapa, Kazuhiro Koshino, Steven P. Rowe, Martin G. Pomper, Mehrbod S. Javadi, Takahiro Higuchi

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 9/2019

Abstract

Although single-photon-emitting radiotracers have long been the standard for renal functional molecular imaging, recent years have seen the development of positron emission tomography (PET) agents for this application. We provide an overview of renal radionuclide PET radiotracers, in particular focusing on novel ¹⁸F-labelled and ⁶⁸Ga-labelled agents. Several reported PET imaging probes allow assessment of glomerular filtration rate, such as [⁶⁸Ga]ethylenediaminetetraacetic acid ([⁶⁸Ga]EDTA), [⁶⁸Ga]IRDye800-tilmanocept and 2-deoxy-2-[¹⁸F]fluorosorbitol ([¹⁸F]FDS)). The diagnostic performance of [⁶⁸Ga]EDTA has already been demonstrated in a clinical trial. [⁶⁸Ga]IRDye800-tilmanocept shows receptor-mediated binding to glomerular mesangial cells, which in turn may allow the monitoring of progression of diabetic nephropathy. [¹⁸F]FDS shows excellent kidney extraction and excretion in rats and, as has been shown in the first study in humans. Further, due to its simple one-step radiosynthesis via the most frequently used PET radiotracer 2-deoxy-2-[¹⁸F]fluoro-d-glucose, [¹⁸F]FDS could be available at nearly every PET centre. A new PET radiotracer has also been introduced for the effective assessment of plasma flow in the kidneys: Re(CO)₃-N-([¹⁸F]fluoroethyl)iminodiacetic acid (Re(CO)₃([¹⁸F]FEDA)). This compound demonstrates similar pharmacokinetic properties to its ^99mTc-labelled analogue [^99mTc](CO)₃(FEDA). Thus, if there is a shortage of molybdenum-99, Re(CO)₃([¹⁸F]FEDA would allow direct comparison with previous studies with ^99mTc. The PET radiotracers for renal imaging reviewed here allow thorough evaluation of kidney function, with the tremendous advantage of precise anatomical coregistration with simultaneously acquired CT images and rapid three-dimensional imaging capability.

Chronic Kidney Disease Prognosis Consortium, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375:2073–81. https://doi.org/10.1016/S0140-6736(10)60674-5.CrossRef

Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012;367:20–9. https://doi.org/10.1056/NEJMoa1114248.CrossRefPubMedPubMedCentral

Blaufox MD. PET measurement of renal glomerular filtration rate: is there a role in nuclear medicine? J Nucl Med. 2016;57:1495–6. https://doi.org/10.2967/jnumed.116.174607.CrossRefPubMed

Soveri I, Berg UB, Bjork J, Elinder CG, Grubb A, Mejare I, et al. Measuring GFR: a systematic review. Am J Kidney Dis. 2014;64:411–24. https://doi.org/10.1053/j.ajkd.2014.04.010.CrossRefPubMed

Chantler C, Garnett ES, Parsons V, Veall N. Glomerular filtration rate measurement in man by the single injection methods using 51Cr-EDTA. Clin Sci. 1969;37:169–80.PubMed

Hofman MS, Hicks RJ. Gallium-68 EDTA PET/CT for renal imaging. Semin Nucl Med. 2016;46:448–61. https://doi.org/10.1053/j.semnuclmed.2016.04.002.CrossRefPubMed

Ma YC, Zuo L, Zhang CL, Wang M, Wang RF, Wang HY. Comparison of 99mTc-DTPA renal dynamic imaging with modified MDRD equation for glomerular filtration rate estimation in Chinese patients in different stages of chronic kidney disease. Nephrol Dial Transplant. 2007;22:417–23. https://doi.org/10.1093/ndt/gfl603.CrossRefPubMed

Gandolpho L, Heilberg IP, Monteiro MC, Schor N. Unilateral hydronephrosis: DMSA and DTPA scan in renal stone formers. In: Ryall R, Bais R, Marshall VR, Rofe AM, Smith LH, Walker VR, editors. Urolithiasis 2. Boston: Springer; 1994.

Sobh M, Neamatallah A, Sheashaa H, Akl A, Osman Y, Gad H, et al. Sobh formula: a new formula for estimation of creatinine clearance in healthy subjects and patients with chronic renal disease. Int Urol Nephrol. 2005;37:403–8. https://doi.org/10.1007/s11255-004-1262-x.CrossRefPubMed

10.

De Santo NG, Anastasio P, Cirillo M, Santoro D, Spitali L, Mansi L, et al. Measurement of glomerular filtration rate by the 99mTc-DTPA renogram is less precise than measured and predicted creatinine clearance. Nephron. 1999;81:136–40. https://doi.org/10.1159/000045268.CrossRefPubMed

11.

Arroyo AJ. Effective renal plasma flow determination using technetium-99m MAG3: comparison of two camera techniques with the Tauxe method. J Nucl Med Technol. 1993;21:162–6.

12.

Werner RA, Beykan S, Higuchi T, Lückerath K, Weich A, Scheurlen M, et al. The impact of 177Lu-octreotide therapy on 99mTc-MAG3 clearance is not predictive for late nephropathy. Oncotarget. 2016;7:41233–41.PubMedPubMedCentral

13.

Hofman M, Binns D, Johnston V, Siva S, Thompson M, Eu P, et al. 68Ga-EDTA PET/CT imaging and plasma clearance for glomerular filtration rate quantification: comparison to conventional 51Cr-EDTA. J Nucl Med. 2015;56:405–9. https://doi.org/10.2967/jnumed.114.147843.CrossRefPubMed

14.

Wakabayashi H, Werner RA, Hayakawa N, Javadi MS, Xinyu C, Herrmann K, et al. Initial preclinical evaluation of 18F-fluorodeoxysorbitol PET as a novel functional renal imaging agent. J Nucl Med. 2016;57:1625–8. https://doi.org/10.2967/jnumed.116.172718.CrossRefPubMed

15.

Werner RA, Wakabayashi H, Chen X, Hirano M, Shinaji T, Lapa C, et al. Functional renal imaging with 2-deoxy-2-(18)F-fluorosorbitol PET in rat models of renal disorders. J Nucl Med. 2018;59:828–32. https://doi.org/10.2967/jnumed.117.203828.CrossRefPubMed

16.

Klenc J, Taylor A, Lipowska M. Synthesis and evaluation of 99mTc(CO)3(FEDA): a new dual-purpose 99mTc/18F renal imaging agent. J Nucl Med. 2015;56 Suppl 3:654.

17.

Lipowska M, Jarkas N, Voll RJ, Nye JA, Klenc J, Goodman MM, et al. Re(CO)3([18F]FEDA), a novel (18)F PET renal tracer: radiosynthesis and preclinical evaluation. Nucl Med Biol. 2018;58:42–50. https://doi.org/10.1016/j.nucmedbio.2017.12.001.CrossRefPubMed

18.

Taylor AT. Radionuclides in nephrourology, part 1: radiopharmaceuticals, quality control, and quantitative indices. J Nucl Med. 2014;55:608–15. https://doi.org/10.2967/jnumed.113.133447.CrossRefPubMedPubMedCentral

19.

Shokeir AA, Gad HM, el-Diasty T. Role of radioisotope renal scans in the choice of nephrectomy side in live kidney donors. J Urol. 2003;170:373–6. https://doi.org/10.1097/01.ju.0000074897.48830.58.CrossRefPubMed

20.

Taylor AT. Radionuclides in nephrourology, part 2: pitfalls and diagnostic applications. J Nucl Med. 2014;55:786–98. https://doi.org/10.2967/jnumed.113.133454.CrossRefPubMedPubMedCentral

21.

Inoue Y, Yoshikawa K, Suzuki T, Katayama N, Yokoyama I, Kohsaka T, et al. Attenuation correction in evaluating renal function in children and adults by a camera-based method. J Nucl Med. 2000;41:823–9.PubMed

22.

Rehling M, Nielsen LE, Marqversen J. Protein binding of 99Tcm-DTPA compared with other GFR tracers. Nucl Med Commun. 2001;22:617–23.CrossRefPubMed

23.

Gundel D, Pohle U, Prell E, Odparlik A, Thews O. Assessing glomerular filtration in small animals using [(68)Ga]DTPA and [(68)Ga]EDTA with PET imaging. Mol Imaging Biol. 2018;20:457–64. https://doi.org/10.1007/s11307-017-1135-1.CrossRefPubMed

24.

Lee JY, Jeong JM, Kim YJ, Jeong HJ, Lee YS, Lee DS, et al. Preparation of Ga-68-NOTA as a renal PET agent and feasibility tests in mice. Nucl Med Biol. 2014;41:210–5. https://doi.org/10.1016/j.nucmedbio.2013.11.005.CrossRefPubMed

25.

Schaer LR, Anger HO, Gottschalk A. Gallium edetate 68Ga experiences in brain-lesion detection with the positron camera. JAMA. 1966;198:811–3.CrossRefPubMed

26.

Abrass CK. Diabetic nephropathy. Mechanisms of mesangial matrix expansion. West J Med. 1995;162:318–21.PubMedPubMedCentral

27.

Qin Z, Hoh CK, Olson ES, Jahromi AH, Hall DJ, Barback CV, et al. Molecular imaging of the glomerulus via mesangial cell uptake of radiolabeled tilmanocept. J Nucl Med. 2019. https://doi.org/10.2967/jnumed.118.223727.

28.

Sanchez-Crespo A. Comparison of gallium-68 and fluorine-18 imaging characteristics in positron emission tomography. Appl Radiat Isot. 2013;76:55–62. https://doi.org/10.1016/j.apradiso.2012.06.034.CrossRefPubMed

29.

Werner RA, Chen X, Hirano M, Rowe SP, Lapa C, Javadi MS, et al. SPECT vs. PET in cardiac innervation imaging: clash of the titans. Clin Transl Imaging. 2018;6:293–303. https://doi.org/10.1007/s40336-018-0289-4.CrossRefPubMedPubMedCentral

30.

Werner RA, Chen X, Rowe SP, Lapa C, Javadi MS, Higuchi T. Recent paradigm shifts in molecular cardiac imaging – establishing precision cardiology through novel 18F-labeled PET radiotracers. Trends Cardiovasc Med. 2019. https://doi.org/10.1016/j.tcm.2019.02.007.

31.

Ducharme J, Goertzen AL, Patterson J, Demeter S. Practical aspects of 18F-FDG PET when receiving 18F-FDG from a distant supplier. J Nucl Med Technol. 2009;37:164–9. https://doi.org/10.2967/jnmt.109.062950.CrossRefPubMed

32.

Kobayashi R, Chen X, Werner RA, Lapa C, Javadi MS, Higuchi T. New horizons in cardiac innervation imaging: introduction of novel (18)F-labeled PET tracers. Eur J Nucl Med Mol Imaging. 2017;44:2302–9. https://doi.org/10.1007/s00259-017-3828-8.CrossRefPubMed

33.

Weinstein EA, Ordonez AA, DeMarco VP, Murawski AM, Pokkali S, MacDonald EM, et al. Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography. Sci Transl Med. 2014;6:259ra146. https://doi.org/10.1126/scitranslmed.3009815.CrossRefPubMedPubMedCentral

34.

Li ZB, Wu Z, Cao Q, Dick DW, Tseng JR, Gambhir SS, et al. The synthesis of 18F-FDS and its potential application in molecular imaging. Mol Imaging Biol. 2008;10:92–8. https://doi.org/10.1007/s11307-007-0125-0.CrossRefPubMed

35.

Li J, Zheng H, Fodah R, Warawa JM, Ng CK. Validation of 2-(18)F-fluorodeoxysorbitol as a potential radiopharmaceutical for imaging bacterial infection in the lung. J Nucl Med. 2018;59:134–9. https://doi.org/10.2967/jnumed.117.195420.CrossRefPubMed

36.

Smith WW, Finkelstein N, Smith NF. Renal excretion of hexitols (sorbitol, mannitol, and dulcitol) and their derivatives (sorbitan, isomannide, and sorbide) and of endogenous creatinine-like chromogen in dog and man. J Biol Chem. 1940;135:231–50.

37.

Klopper JF, Hauser W, Atkins HL, Eckelman WC, Richards P. Evaluation of 99m Tc-DTPA for the measurement of glomerular filtration rate. J Nucl Med. 1972;13:107–10.PubMed

38.

Rehling M. Stability, protein binding and clearance studies of [99mTc]DTPA. Evaluation of a commercially available dry-kit. Scand J Clin Lab Invest. 1988;48:603–9.CrossRefPubMed

39.

Gordon I, Piepsz A, Sixt R, Auspices of Paediatric Committee of European Association of Nuclear Medicine. Guidelines for standard and diuretic renogram in children. Eur J Nucl Med Mol Imaging. 2011;38:1175–88. https://doi.org/10.1007/s00259-011-1811-3.CrossRefPubMed

40.

Werner RA, Ordonez AA, Sanchez-Bautista J, Marcus C, Lapa C, Rowe SP, et al. Novel functional renal PET imaging with 18F-FDS in human subjects. Clin Nucl Med. 2019;44:410–1. https://doi.org/10.1097/RLU.0000000000002494.CrossRefPubMed

41.

Lipowska M, Klenc J, Jarkas N, Marzilli LG, Taylor AT. Monoanionic (99m)Tc-tricarbonyl-aminopolycarboxylate complexes with uncharged pendant groups: radiosynthesis and evaluation as potential renal tubular tracers. Nucl Med Biol. 2017;47:48–55. https://doi.org/10.1016/j.nucmedbio.2016.12.008.CrossRefPubMed

42.

Eshima D, Fritzberg AR, Taylor A Jr. 99mTc renal tubular function agents: current status. Semin Nucl Med. 1990;20:28–40.CrossRefPubMed

43.

Lipowska M, Klenc J, Shetty D, Nye JA, Shim H, Taylor AT. Al18F-NODA-butyric acid: biological evaluation of a new PET renal radiotracer. Nucl Med Biol. 2014;41:248–53. https://doi.org/10.1016/j.nucmedbio.2013.12.010.CrossRefPubMed

44.

Awasthi V, Pathuri G, Agashe HB, Gali H. Synthesis and in vivo evaluation of p-18F-fluorohippurate as a new radiopharmaceutical for assessment of renal function by PET. J Nucl Med. 2011;52:147–53. https://doi.org/10.2967/jnumed.110.075895.CrossRefPubMed

45.

Pathuri G, Sahoo K, Awasthi V, Gali H. Renogram comparison of p-[(18)F]fluorohippurate with o-[(125)I]iodohippurate and [(99m)Tc]MAG3 in normal rats. Nucl Med Commun. 2011;32:908–12. https://doi.org/10.1097/MNM.0b013e32834a6db6.CrossRefPubMed

46.

Pathuri G, Hedrick A, Awasthi V, Cowley B, Gali H. Evaluation of Para-18F-fluorohippurate PET renography to predict future disease progression in a rat model of ADPKD. J Nucl Med. 2015;56:1077.

47.

Geist BK, Baltzer P, Fueger B, Hamboeck M, Nakuz T, Papp L, et al. Assessing the kidney function parameters glomerular filtration rate and effective renal plasma flow with dynamic FDG-PET/MRI in healthy subjects. EJNMMI Res. 2018;8:37. https://doi.org/10.1186/s13550-018-0389-1.CrossRefPubMedPubMedCentral

48.

Szabo Z, Xia J, Mathews WB, Brown PR. Future direction of renal positron emission tomography. Semin Nucl Med. 2006;36:36–50. https://doi.org/10.1053/j.semnuclmed.2005.08.003.CrossRefPubMedPubMedCentral

49.

Hanssen O, Erpicum P, Lovinfosse P, Meunier P, Weekers L, Tshibanda L, et al. Non-invasive approaches in the diagnosis of acute rejection in kidney transplant recipients. Part I. In vivo imaging methods. Clin Kidney J. 2017;10:97–105. https://doi.org/10.1093/ckj/sfw062.CrossRefPubMed

50.

Hartlev LB, Boeje CR, Bluhme H, Palshof T, Rehling M. Monitoring renal function during chemotherapy. Eur J Nucl Med Mol Imaging. 2012;39:1478–82. https://doi.org/10.1007/s00259-012-2158-0.CrossRefPubMed

51.

Jackson P, Foroudi F, Pham D, Hofman MS, Hardcastle N, Callahan J, et al. Short communication: timeline of radiation-induced kidney function loss after stereotactic ablative body radiotherapy of renal cell carcinoma as evaluated by serial (99m)Tc-DMSA SPECT/CT. Radiat Oncol. 2014;9:253. https://doi.org/10.1186/s13014-014-0253-z.CrossRefPubMedPubMedCentral

52.

Weinberger S, Bader M, Scheurig-Munkler C, Hinz S, Neymeyer J, Miller K, et al. Optimizing evaluation of split renal function in a living kidney donor using scintigraphy and calculation of the geometric mean: a case report. Case Rep Nephrol Urol. 2014;4:1–4. https://doi.org/10.1159/000358007.CrossRefPubMedPubMedCentral

53.

Weinberger S, Baeder M, Scheurig-Muenkler C, Steffen IG, Magheli A, Miller K, et al. Optimizing scintigraphic evaluation of split renal function in living kidney donors using the geometric mean method: a preliminary retrospective study. J Nephrol. 2016;29:435–41. https://doi.org/10.1007/s40620-015-0223-z.CrossRefPubMed

54.

Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al. Phase 3 trial of (177)Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376:125–35. https://doi.org/10.1056/NEJMoa1607427.CrossRefPubMedPubMedCentral

55.

Maurer S, Herhaus P, Lippenmeyer R, Hanscheid H, Kircher M, Schirbel A, et al. Side effects of CXC-chemokine receptor 4-directed endoradiotherapy with pentixather prior to hematopoietic stem cell transplantation. J Nucl Med. 2019. https://doi.org/10.2967/jnumed.118.223420.

56.

Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [(177)Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19:825–33. https://doi.org/10.1016/S1470-2045(18)30198-0.CrossRefPubMed

57.

Williams B, Tareen B, Resnick MI. Pathophysiology and treatment of ureteropelvic junction obstruction. Curr Urol Rep. 2007;8:111–7.CrossRefPubMed

58.

Werner RA, Bluemel C, Lassmann M, Kudlich T, Higuchi T, Lopci E, et al. SPECT- and PET-based patient-tailored treatment in neuroendocrine tumors: a comprehensive multidisciplinary team approach. Clin Nucl Med. 2015;40:e271–7. https://doi.org/10.1097/RLU.0000000000000729.CrossRefPubMed

59.

Rowe SP, Gorin MA, Allaf ME, Pienta KJ, Tran PT, Pomper MG, et al. PET imaging of prostate-specific membrane antigen in prostate cancer: current state of the art and future challenges. Prostate Cancer Prostatic Dis. 2016;19:223–30. https://doi.org/10.1038/pcan.2016.13.CrossRefPubMedPubMedCentral

60.

Werner RA, Andree C, Javadi MS, Lapa C, Buck AK, Higuchi T, et al. A voice from the past: rediscovering the Virchow node with prostate-specific membrane antigen-targeted (18)F-DCFPyL positron emission tomography imaging. Urology. 2018;117:18–21. https://doi.org/10.1016/j.urology.2018.03.030.CrossRefPubMedPubMedCentral

Title: The next era of renal radionuclide imaging: novel PET radiotracers
Authors: Rudolf A. Werner
Xinyu Chen
Constantin Lapa
Kazuhiro Koshino
Steven P. Rowe
Martin G. Pomper
Mehrbod S. Javadi
Takahiro Higuchi
Publication date: 01-08-2019
Publisher: Springer Berlin Heidelberg
Keyword: Positron Emission Tomography
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 9/2019
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-019-04359-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The next era of renal radionuclide imaging: novel PET radiotracers

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 9/2019

Direct comparison of the in vitro and in vivo stability of DFO, DFO* and DFOcyclo* for 89Zr-immunoPET

Early lesion detection with 18F-DCFPyL PET/CT in 248 patients with biochemically recurrent prostate cancer

68Ga-PSMA-11 PET/CT in a patient with non-PSA-secreting undifferentiated prostate cancer before and after treatment with cabozantinib

Synthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A)

Increase of precuneus metabolism correlates with reduction of PTSD symptoms after EMDR therapy in military veterans: an 18F-FDG PET study during virtual reality exposure to war

Abdelhamid H Elgazzar, Ismet Sarikaya (Eds): Nuclear Medicine Companion. A Case-Based Practical Reference for Daily Use