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68Ga-PSMA-11 dynamic PET/CT imaging in biochemical relapse of prostate cancer

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Objectives

We aim to investigate the pharmacokinetics and distribution of the recently clinically introduced radioligand 68Ga-PSMA-11 in men with recurrent prostate cancer (PC) by means of dynamic and whole-body PET/CT. The correlation between PSA levels and 68Ga-PSMA-11 PET parameters is also investigated.

Methods

31 patients with biochemical failure after primary PC treatment with curative intent (median age 71.0 years) were enrolled in the analysis. The median PSA value was 2.0 ng/mL (range = 0.1 – 130.0 ng/mL) and the median Gleason score was 7 (range = 5 – 9). 8/31 (25.8 %) of the included patients had a PSA value < 0.5 ng/ml. All patients underwent dynamic PET/CT (dPET/CT) scanning (60 min) of the pelvis and lower abdomen as well as whole-body PET/CT with 68Ga-PSMA-11. dPET/CT assessment was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a two-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD).

Results

22/31 patients (71.0 %) were 68Ga-PSMA-11-positive, while 9/31 (29.0 %) patients were 68Ga-PSMA-11-negative. The median PSA value in the 68Ga-PSMA-11-positive group was significantly higher (median = 2.35 ng/mL; range = 0.19 – 130.0 ng/mL) than in the 68Ga-PSMA-11-negative group (median value: 0.34 ng/mL; range = 0.10 – 4.20 ng/mL). A total of 76 lesions were semi-quantitatively evaluated. PC recurrence-associated lesions demonstrated a mean SUVaverage = 12.4 (median = 9.0; range = 2.2 – 84.5) and mean SUVmax = 18.8 (median = 14.1; range = 3.1 – 120.3). Dynamic PET/CT studies of the pelvis revealed the following mean values for the PC recurrence-suspicious lesions: K1 = 0.26, k3 = 0.30, influx = 0.14 and FD = 1.24. Time–activity curves derived from PC-recurrence indicative lesions revealed an increasing 68Ga-PSMA-11 accumulation during dynamic PET acquisition. Correlation analysis revealed a moderate, but significant, correlation between PSA levels and the number of lesions detected on 68Ga-PSMA-11 PET/CT (r = 0.54) and between PSA levels and SUVaverage (r = 0.48) or SUVmax (r = 0.44).

Conclusions

Ga-PSMA-11 PET/CT demonstrated an overall detection rate of 71.0 % 60 min p.i. of the radiotracer in a mixed patient population with respect to PSA levels and including patients with very low PSA values. Higher PSA values were associated with a higher detection rate. The tracer uptake in PC-recurrence-indicative lesions is increasing during the 60 minutes of dynamic PET acquisition.

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References

  1. Roehl KA, Han M, Ramos CG, Antenor JA, Catalona WJ. Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3,478 consecutive patients: long- term results. J Urol. 2004;172:910–4.

    Article  PubMed  Google Scholar 

  2. Nguyen QN, Levy LB, Lee AK, Choi SS, Frank SJ, Pugh TJ, et al. Long-term outcomes for men with high-risk prostate cancer treated definitively with external beam radiotherapy with or without androgen deprivation. Cancer. 2013;119:3265–71.

    Article  CAS  PubMed  Google Scholar 

  3. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281:1591–7.

    Article  CAS  PubMed  Google Scholar 

  4. Kamat AM, Rosser CJ, Levy LB, et al. Rise in serum PSA of 1.5 ng/mL above 24-month nadir after external beam radiotherapy is predictive of biochemical failure. Urology. 2004;63:1132–7.

    Article  PubMed  Google Scholar 

  5. Bott SR. Management of recurrent disease after radical prostatectomy. Prostate Cancer Prostatic Dis. 2004;7:211–6.

    Article  CAS  PubMed  Google Scholar 

  6. Beer AJ, Eiber M, Souvatzoglou M, Schwaiger M, Krause BJ. Radionuclide and hybrid imaging of recurrent prostate cancer. Lancet Oncol. 2011;12:181–91.

    Article  PubMed  Google Scholar 

  7. Johnstone PA, Tarman GJ, Riffenburgh R, Rohde DC, Puckett ML, Kane CJ. Yield of imaging and scintigraphy assessing biochemical failure in prostate cancer patients. Urol Oncol. 1997;3:108–12.

    Article  CAS  PubMed  Google Scholar 

  8. Cher ML, Bianco Jr FJ, Lam JS, et al. Limited role of radionuclide bone scintigraphy in patients with prostate specific antigen elevations after radical prostatectomy. J Urol. 1998;160:1387–91.

    Article  CAS  PubMed  Google Scholar 

  9. Heinisch M, Dirisamer A, Loidl W, et al. Positron emission tomography/computed tomography with F-18-fluorocholine for restaging of prostate cancer patients: meaningful at PSA < 5 ng/ml? Mol Imaging Biol. 2006;8:43–8.

    Article  PubMed  Google Scholar 

  10. Krause BJ, Souvatzoglou M, Tuncel M, et al. The detection rate of [11C]choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer. Eur J Nucl Med Mol Imaging. 2008;35:18–23.

    Article  CAS  PubMed  Google Scholar 

  11. Ceci F, Herrmann K, Castellucci P, et al. Impact of 11C-choline PET/CT on clinical decision making in recurrent prostate cancer: results from a retrospective two-centre trial. Eur J Nucl Med Mol Imaging. 2014;41:2222–31.

    Article  PubMed  Google Scholar 

  12. Schmid DT, John H, Zweifel R, et al. Fluorocholine PET/CT in patients with prostate cancer: initial experience. Radiology. 2005;235:623–8.

    Article  PubMed  Google Scholar 

  13. Vees H, Buchegger F, Albrecht S, et al. 18F-choline and/or 11C-acetate positron emission tomography: detection of residual or progressive subclinical disease at very low prostate-specific antigen values (<1 ng/mL) after radical prostatectomy. BJU Int. 2007;99:1415–20.

    Article  CAS  PubMed  Google Scholar 

  14. Igerc I, Kohlfürst S, Gallowitsch HJ, et al. The value of 18F-choline PET/CT in patients with elevated PSA-level and negative prostate needle biopsy for localisation of prostate cancer. Eur J Nucl Med Mol Imaging. 2008;35:976–83.

    Article  CAS  PubMed  Google Scholar 

  15. Kwee SA, DeGrado T. Prostate biopsy guided by 18F-fluorocholine PET in men with persistently elevated PSA levels. Eur J Nucl Med Mol Imaging. 2008;35:1567–9.

    Article  PubMed  Google Scholar 

  16. Husarik DB, Miralbell R, Dubs M, et al. Evaluation of [(18)F]-choline PET/CT for staging and restaging of prostate cancer. Eur J Nucl Med Mol Imaging. 2008;35:253–63.

    Article  PubMed  Google Scholar 

  17. Afshar-Oromieh A, Malcher A, Eder M, et al. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging. 2013;40:486–95.

    Article  CAS  PubMed  Google Scholar 

  18. Afshar-Oromieh A, Avtzi E, Giesel FL, 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;42:197–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Eiber M, Maurer T, Souvatzoglou M, et al. Evaluation of hybrid 68Ga-PSMA-ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56:668–74.

    Article  PubMed  Google Scholar 

  20. Yu CY, Desai B, Ji L, Groshen S, Jadvar H. Comparative performance of PET tracers in biochemical recurrence of prostate cancer: a critical analysis of literature. Am J Nucl Med Mol Imaging. 2014;4:580–601.

    PubMed  PubMed Central  Google Scholar 

  21. Afshar-Oromieh A, Zechmann CM, Malcher A, et al. Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41:11–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Morigi JJ, Stricker PD, van Leeuwen PJ, et al. Prospective comparison of 18F-fluoromethylcholine versus 68Ga-PSMA PET/CT in prostate cancer patients Who have rising PSA after curative treatment and Are being considered for targeted therapy. J Nucl Med. 2015;56:1185–90.

    Article  CAS  PubMed  Google Scholar 

  23. Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997;3:81–5.

    CAS  PubMed  Google Scholar 

  24. Osborne JR, Akhtar NH, Vallabhajosula S, Anand A, Deh K, Tagawa ST. Prostate-specific membrane antigen-based imaging. Urol Oncol. 2013;3:144–54.

    Article  Google Scholar 

  25. Ghosh A, Heston WD. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem. 2004;91:528–39.

    Article  CAS  PubMed  Google Scholar 

  26. Eder M, Eisenhut M, Babich J, Haberkorn U. PSMA as a target for radiolabelled small molecules. Eur J Nucl Med Mol Imaging. 2013;40:819–23.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Epstein JI, Pizov G, Walsh PC. Correlation of pathologic findings with progression after radical retropubic prostatectomy. Cancer. 1993;71:3582–93.

    Article  CAS  PubMed  Google Scholar 

  28. Freedland SJ, Sutter ME, Dorey F, Aronson WJ. Defining the ideal cutpoint for determining PSA recurrence after radical prostatectomy Prostate-specific antigen. Urology. 2003;61:365–9.

    Article  PubMed  Google Scholar 

  29. Eder M, Schäfer M, Bauder-Wüst U, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem. 2012;23:688–97.

    Article  CAS  PubMed  Google Scholar 

  30. Eder M, Neels O, Müller 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;7:779–96.

    Article  CAS  Google Scholar 

  31. Schumacher J, Maier-Borst W. A new 68Ge/68Ga radioisotope generator system for production of 68Ga in dilute HCL. Int J Appl Radiat Isot. 1981;32:31–6.

    Article  Google Scholar 

  32. Schäfer M, Bauder-Wüst U, Leotta K, et al. A dimerized urea-based inhibitor of the prostate-specific membrane antigen for 68Ga-PET imaging of prostate cancer. EJNMMI Res. 2012;2:23.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Dimitrakopoulou-Strauss A, Pan L, Strauss LG. Quantitative approaches of dynamic FDG-PET and PET/CT studies (dPET/CT) for the evaluation of oncological patients. Cancer Imaging. 2012;12:283–9.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Strauss LG, Conti PS. The applications of PET in clinical oncology. J Nucl Med. 1991;32:623–48.

    CAS  PubMed  Google Scholar 

  35. Burger C, Buck A. Requirements and implementations of a flexible kinetic modeling tool. J Nucl Med. 1997;38:1818–23.

    CAS  PubMed  Google Scholar 

  36. Mikolajczyk K, Szabatin M, Rudnicki P, Grodzki M, Burger C. A Java environment for medical image data analysis: initial application for brain PET quantitation. Med Inform. 1998;23:207–14.

    Article  CAS  Google Scholar 

  37. Sokoloff L, Smith CB. Basic principles underlying radioisotopic methods for assay of biochemical processes in vivo. In: Greitz T, Ingvar DH, Widén L, editors. The metabolism of the human brain studied with positron emission tomography. New York: Raven Press; 1983. p. 123–48.

    Google Scholar 

  38. Miyazawa H, Osmont A, Petit-Taboué MC, et al. Determination of 18F-fluoro-2-deoxy-D-glucose rate constants in the anesthetized baboon brain with dynamic positron tomography. J Neurosci Methods. 1993;50:263–72.

    Article  CAS  PubMed  Google Scholar 

  39. Ohtake T, Kosaka N, Watanabe T, et al. Noninvasive method to obtain input function for measuring tissue glucose utilization of thoracic and abdominal organs. J Nucl Med. 1991;32:1432–8.

    CAS  PubMed  Google Scholar 

  40. Strauss LG, Klippel S, Pan L, Schönleben K, Haberkorn U, Dimitrakopoulou-Strauss A. Assessment of quantitative FDG PET data in primary colorectal tumours: which parameters are important with respect to tumour detection? Eur J Nucl Med Mol Imaging. 2007;34:868–77.

    Article  PubMed  Google Scholar 

  41. Koukouraki S, Strauss LG, Georgoulias V, et al. Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy. Eur J Nucl Med Mol Imaging. 2006;33:460–6.

    Article  CAS  PubMed  Google Scholar 

  42. Dimitrakopoulou-Strauss A, Seiz M, Tuettenberg J, Schmieder K, Eisenhut M, Haberkorn U, et al. Pharmacokinetic studies of 68Ga-labeled bombesin (68Ga-BZH3) and F-18 FDG PET in patients with recurrent gliomas and comparison to grading: preliminary results. Clin Nucl Med. 2011;36:101–8.

    Article  PubMed  Google Scholar 

  43. Galli G, Indovina L, Calcagni ML, Mansi L, Giordano A. The quantification with FDG as seen by a physician. Nucl Med Biol. 2013;40:720–30.

    Article  CAS  PubMed  Google Scholar 

  44. Guo N, Lang L, Gao H, Niu G, Kiesewetter DO, et al. Quantitative analysis and parametric imaging of 18F-labeled monomeric and dimeric RGD peptides using compartment model. Mol Imaging Biol. 2012;14:743–52.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Dimitrakopoulou-Strauss A, Strauss LG, Burger C, Mikolajczyk K, Lehnert T, et al. On the fractal nature of positron emission tomography (PET) studies. World J Nucl Med. 2003;4:306–13.

    Google Scholar 

  46. Ceci F, Uprimny C, Nilica B, et al. 68Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate? Eur J Nucl Med Mol Imaging. 2015;42:1284–94.

    Article  PubMed  Google Scholar 

  47. Mannweiler S, Amersdorfer P, Trajanoski S, Terrett JA, King D, Mehes G. Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis. Pathol Oncol Res. 2009;15:167–72.

    Article  CAS  PubMed  Google Scholar 

  48. Miyamoto DT, Sequist LV, Lee RJ. Circulating tumour cells-monitoring treatment response in prostate cancer. Nat Rev Clin Oncol. 2014;11:401–12.

    Article  CAS  PubMed  Google Scholar 

  49. Henze M, Dimitrakopoulou-Strauss A, Milker-Zabel S, et al. Characterization of 68Ga-DOTA-D-Phe1-Tyr3-octreotide kinetics in patients with meningiomas. J Nucl Med. 2005;46:763–9.

    CAS  PubMed  Google Scholar 

  50. Zechmann CM, Afshar-Oromieh A, Armor T, et al. Radiation dosimetry and first therapy results with a (124)I/ (131)I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy. Eur J Nucl Med Mol Imaging. 2014;41:1280–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Benešová M, Schäfer M, Bauder-Wüst U, et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med. 2015;56:914–20.

    Article  PubMed  Google Scholar 

  52. Afshar-Oromieh A, Hetzheim H, Kratochwil C, et al. The theranostic PSMA ligand PSMA-617 in the diagnosis of prostate cancer by PET/CT: Biodistribution in humans, radiation dosimetry, and first evaluation of tumor lesions. J Nucl Med. 2015;56:1697–705.

    Article  CAS  PubMed  Google Scholar 

  53. Dey P. Basic principles and applications of fractal geometry in pathology: a review. Anal Quant Cytol Histol. 2005;27:284–90.

    PubMed  Google Scholar 

  54. Koukouraki S, Strauss LG, Georgoulias V, et al. Comparison of the pharmacokinetics of 68Ga-DOTATOC and [18F]FDG in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy. Eur J Nucl Med Mol Imaging. 2006;33:1115–22.

    Article  CAS  PubMed  Google Scholar 

  55. Sachpekidis C, Goldschmidt H, Hose D, et al. PET/CT studies of multiple myeloma using (18) F-FDG and (18) F-NaF: comparison of distribution patterns and tracers' pharmacokinetics. Eur J Nucl Med Mol Imaging. 2014;41:1343–53.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Heidelberg, Germany

    C. Sachpekidis, U. Haberkorn & A. Dimitrakopoulou-Strauss

  2. Division of Radiopharmaceutical Chemistry, German Cancer Research Center (DKFZ), Heidelberg, Germany

    M. Eder & K. Kopka

  3. German Cancer Consortium (DKTK), Heidelberg, Germany

    K. Kopka & U. Haberkorn

  4. Division of Nuclear Medicine, University of Heidelberg, Heidelberg, Germany

    W. Mier & U. Haberkorn

  5. Department of Urology, University Hospital Heidelberg, Heidelberg, Germany

    B. A. Hadaschik

  6. Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Im Neuenheimer Feld 280, D-69210, Heidelberg, Germany

    C. Sachpekidis

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  1. C. Sachpekidis
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Sachpekidis, C., Eder, M., Kopka, K. et al. 68Ga-PSMA-11 dynamic PET/CT imaging in biochemical relapse of prostate cancer. Eur J Nucl Med Mol Imaging 43, 1288–1299 (2016). https://doi.org/10.1007/s00259-015-3302-4

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  • DOI: https://doi.org/10.1007/s00259-015-3302-4

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