Contribution of 68Ga-PSMA PET/CT to targeting volume delineation of prostate cancer treated with conformal radiation therapy: Which SUV threshold is appropriate?

Document Type : Original Article


1 Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran

2 Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran

3 Nuclear Medicine Department, Razavi Hospital, Imam Reza International University, Mashhad, Iran

4 Cancer Research Center, Omid Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5 Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

6 Medical Physics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

7 Nuclear Medicine Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


Introduction: Prostate-specific membrane antigen (PSMA) has been demonstrated as a promising tool for specific imaging of prostate cancer (PCa) via positron emission tomography-computed tomography (PET/CT) scanning. Radiation treatment planning (RTP) based on 68Ga-PSMA PET/CT scanning can also lead to some decision modifications.  The specific goal of this comparative study is to show how 68Ga-PSMA PET/CT images can influence the target volume delineation (TVD) and normal tissue radiation dose for PCa RTP, and to compare gross tumor volumes (GTVs) delineated using various strategies for 68Ga-PSMA PET-based image segmentation techniques.
Methods: This study consisted of eleven 68Ga-PSMA PET/CT images related to patients affected with locally advanced PCa. Four strategies also included manual segmentation techniques, a 2.5 standardized uptake value (SUV) cutoff (SUV=2.5), as well as a fixed threshold of 40% and 50% of the maximum signal intensity (SUV=%40 SUVmax and SUV=%50 SUVmax) for 68Ga-PSMA PET-based segmentation techniques to delineate GTVPET. Two treatment planning were accordingly generated for each patient based on manual GTVPET and CT-only.
Results: The GTV was statistically and significantly smaller for PET/CT-derived volumes (9.39 vs. 77.98 cm3 for CT alone) (p<0.002). There was no significant difference in volumes of GTV2.5 and GTV40% with GTVman (p=0.11) although we observed a significant difference in volumes of GTV50% with GTVman (p=0.02). Mean bladder dose (MBD), V50 of rectum, and mean femoral dose (MFD) for PET/CT plans were significantly lower than CT-only (22.36 vs. 46.55 Gy; p=0.004), (33% vs. 67.82%; p=0.000), and (28.01 vs. 37.12Gy; p=0.013); respectively.
Conclusion: The contribution of hybrid modalities of PSMA-PET/CT can be useful for detailed target volume planning and reduce radiation exposure to organs at risk. Using molecular images in RTP also demonstrates the biological volume of GTV so that it will not be left out of the field to cause recurrent tumor.


Main Subjects

  1. Vinsensia M, Chyoke PL, Hadaschik B, Holland-Letz T, Moltz J, Kopka K, Rauscher I, Mier W, Schwaiger M, Haberkorn U, Mauer T, Kratochwil C, Eiber M, Giesel FL. 68Ga-PSMA PET/CT and volumetric morphology of PET-positive lymph nodes stratified by tumor differentiation of prostate cancer. J Nucl Med. 2017 Dec;58(12):1949-1955.
  2. Gupta M, Choudhury PS, Hazarika D, Rawal S. A comparative study of 68Gallium-prostate specific membrane antigen positron emission tomography-computed tomography and magnetic resonance imaging for lymph node staging in high risk prostate cancer patients: an initial experience. World J Nucl Med. 2017 Jul-Sep;16(3):186-191.
  3. Öbek C, Doğanca T, Demirci E, Ocak M, Kural AR, Yıldırım A, Yücetaş U, Demirdağ Ç, Erdoğan SM, Kabasakal L; Members of Urooncology Association, Turkey. The accuracy of 68 Ga-PSMA PET/CT in primary lymph node staging in high-risk prostate cancer. Eur J Nucl Med Mol Imaging. 2017 Oct;44(11):1806-1812.
  4. Toloza EM, Harpole L, McCrory DC. Noninvasive staging of non-small cell lung cancer: a review of the current evidence. Chest. 2003 Jan;123(1 Suppl):137S-146S.
  5. MacManus M, Nestle U, Rosenzweig KE, Carrio I, Messa C, Belohlavek O, Danna M, Inoue T, Deniaud-Alexandre E, Schipani S, Watanabe N, Dondi M, Jeremic B. Use of PET and PET/CT for radiation therapy planning: IAEA expert report 2006–2007. Radiother Oncol. 2009 Apr;91(1):85-94.
  6. Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, Kubler H, Haberkorn U, Eisenhut M, Wester HJ, Gschwend JE, Schwaiger M. Evaluation of hybrid 68Ga-PSMA-ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56(5):668-674.
  7. Afshar-Oromieh A, Avtzi E, Giesel F, Holland-Letz T, Linhart H, Eder M, Eisenhut M, Boxler S, Hadaschik B, Kratochwil K, Weichert W, Kopka K, Debus J, Haberkorn U. 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.
  8. Afshar-Oromieh A, Zechmann C, Malcher A, Eder M, Eisenhut M, Linhart H, Holland-Letz T, Hadaschik B, Giesel F, Debus J, Haberkorn U. 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(1):11-20.
  9. Schiller K, Devecka M, Maurer T, Eiber M, Gschwend J, Schwaiger M, Combs SE, Habl G. Impact of 68 Ga-PSMA-PET imaging on target volume definition and guidelines in radiation oncology-a patterns of failure analysis in patients with primary diagnosis of prostate cancer. Radiat Oncol. 2018 Mar 1;13(1):36.
  10. Bradley J, Bae K, Choi N, Forster K, Siegel BA, Brunetti J, Purdy J, Faria S, Vu T, Thorstad W, Choy H. A phase II comparative study of gross tumor volume definition with or without PET/CT fusion in dosimetric planning for non–small-cell lung cancer (NSCLC): primary analysis of Radiation Therapy Oncology Group (RTOG) 0515. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):435-41.e1.
  11. Bradley JD, Perez CA, Dehdashti F, Siegel BA. Implementing biologic target volumes in radiation treatment planning for non-small cell lung cancer. The J Nucl Med. 2004 Jan;45 Suppl 1:96S-101S.
  12. Fiorentino A, Laudicella R, Ciurlia E, Annunziata S, Lancellotta V, Mapelli P, Tuscano C, Caobelli F, Evangelista L, Marino L, Quartuccio N, Fiore M, Borghetti P, Chiaravalloti A, Ricci M, Desideri I, Alongi P; AIRO Giovani - Italian Association of Radiation Oncology-Young Members and AIMN -Italian Association of Nuclear Medicine- Young Members Working Group. Positron emission tomography with computed tomography imaging (PET/CT) for the radiotherapy planning definition of the biological target volume: PART 2. Crit Rev Oncol Hematol. 2019 Jul;139:117-124.
  13. Menon H, Guo C, Verma V, Simone CB 2nd. The Role of positron emission tomography imaging in radiotherapy target delineation. PET Clin. 2020 Jan;15(1):45-53.
  14. Morigi JJ, Anderson J, Fanti S. Promise of PET imaging in prostate cancer: improvement or waste of money? Curr Opin Urol. 2020 Jan;30(1):9-16.
  15. Nestle U, Walter K, Schmidt S, Licht N, Nieder C, Motaref B, Hellwig D, Niewald M, Ukena D, Kirsch CM, Sybrecht GW, Schnabel K. 18F-deoxyglucose positron emission tomography (FDG-PET) for the planning of radiotherapy in lung cancer: high impact in patients with atelectasis. Int J Radiat Oncol Biol Phys. 1999 Jun 1;44(3):593-7.
  16. Munley MT, Marks LB, Scarfone C, Sibley GS, Patz EF Jr, Turkington TG, Jaszczak RJ, Gilland DR, Anscher MS, Coleman RE. Multimodality nuclear medicine imaging in radiation treatment planning for lung cancer: challenges and prospects. Lung Cancer. 1999 Feb;23(2):105-14.
  17. Mac Manus MP, Hicks RJ, Ball DL, Kalff V, Matthews JP, Salminen E, Khaw P, Wirth A, Rischin D, McKenzie A. F‐18 fluorodeoxyglucose positron emission tomography staging in radical radiotherapy candidates with nonsmall cell lung carcinoma: powerful correlation with survival and high impact on treatment. Cancer. 2001 Aug 15;92(4):886-95.
  18. Zamboglou C, Fassbender TF, Steffan L, Schiller F, Fechter T, Carles M, Kiefer S, Rischke HC, Reichel K, Schmidt-Hegemann NS, Ilhan H, Chirindel AF, Nicolas G, Henkenberens C, Derlin T, Bronsert P, Mavroidis P, Chen RC, Meyer PT, Ruf J, Grosu AL. Validation of different PSMA-PET/CT-based contouring techniques for intraprostatic tumor definition using histopathology as standard of reference. Radiother Oncol. 2019 Dec;141:208-213.
  19. Li H, Thorstad WL, Biehl KJ, Laforest R, Su Y, Shoghi KI, Donnelly ED, Low DA, Lu W. A novel PET tumor delineation method based on adaptive region‐growing and dual‐front active contours. Med Phys. 2008 Aug;35(8):3711-21.
  20. Montgomery DW, Amira A, Zaidi H. Fully automated segmentation of oncological PET volumes using a combined multiscale and statistical model. Med Phys. 2007 Feb;34(2):722-36.
  21. Geets X, Lee JA, Bol A, Lonneux M, Grégoire V. A gradient-based method for segmenting FDG-PET images: methodology and validation. Eur J Nucl Med Mol Imaging. 2007 Sep;34(9):1427-38.
  22. van Baardwijk A, Bosmans G, Boersma L, Buijsen J, Wanders S, Hochstenbag M, van Suylen RJ, Dekker A, Dehing-Oberije C, Houben R, Bentzen SM, van Kroonenburgh M, Lambin P, De Ruysscher D. PET-CT-based auto-contouring in non-small-cell lung cancer correlates with pathology and reduces interobserver variability in the delineation of the primary tumor and involved nodal volumes. Int J Radiat Oncol Biol Phys. 2007 Jul 1;68(3):771-8.
  23. Abedi I, Tavakkoli MB, Jabbari K, Amouheidari A, Yadegarfard G. Dosimetric and radiobiological evaluation of multiparametric mri-guided dose painting in radiotherapy of prostate cancer. J Med Signals Sens. 2017 Apr-Jun;7(2):114-121.
  24. Zaidi H, El Naqa I. PET-guided delineation of radiation therapy treatment volumes: a survey of image segmentation techniques. Eur J Nucl Med Mol Imaging. 2010 Nov;37(11):2165-87.
  25. Ciernik IF, Dizendorf E, Baumert BG, Reiner B, Burger C, Davis JB, Lütolf UM, Steinert HC, Von Schulthess GK. Radiation treatment planning with an integrated positron emission and computer tomography (PET/CT): a feasibility study. Int J Radiat Oncol Biol Phys. 2003 Nov 1;57(3):853-63.
  26. Paulino AC, Koshy M, Howell R, Schuster D, Davis LW. Comparison of CT-and FDG-PET-defined gross tumor volume in intensity-modulated radiotherapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2005 Apr 1;61(5):1385-92.
  27. Wang D, Schultz CJ, Jursinic PA, Bialkowski M, Zhu XR, Brown WD, Rand SD, Michel MA, Campbell BH, Wong S, Li XA, Wilson JF. Initial experience of FDG-PET/CT guided IMRT of head-and-neck carcinoma. Int J Radiat Oncol Biol Phys. 2006 May 1;65(1):143-51.
  28. Konert T, Vogel W, MacManus MP, Nestle U, Belderbos J, Grégoire V, Thorwarth D, Fidarova E, Paez D, Chiti A, Hanna GG. PET/CT imaging for target volume delineation in curative intent radiotherapy of non-small cell lung cancer: IAEA consensus report 2014. Radiother Oncol. 2015 Jul;116(1):27-34.
  29. Cannon DM, Lee NY. Recurrence in region of spared parotid gland after definitive intensity-modulated radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 2008 Mar 1;70(3):660-5.
  30. Vees H, Senthamizhchelvan S, Miralbell R, Weber DC, Ratib O, Zaidi H. Assessment of various strategies for 18 F-FET PET-guided delineation of target volumes in high-grade glioma patients. Eur J Nucl Med Mol Imaging. 2009 Feb;36(2):182-93.
  31. Hong R, Halama J, Bova D, Sethi A, Emami B. Correlation of PET standard uptake value and CT window-level thresholds for target delineation in CT-based radiation treatment planning. Int J Radiat Oncol Biol Phys. 2007 Mar 1;67(3):720-6.
  32. Yu W, Fu XL, Zhang YJ, Xiang JQ, Shen L, Jiang GL, Chang JY. GTV spatial conformity between different delineation methods by 18FDG PET/CT and pathology in esophageal cancer. Radiother Oncol. 2009 Dec;93(3):441-6.
  33. Wanet M, Lee JA, Weynand B, De Bast M, Poncelet A, Lacroix V, Coche E, Grégoire V, Geets X. Gradient-based delineation of the primary GTV on FDG-PET in non-small cell lung cancer: a comparison with threshold-based approaches, CT and surgical specimens. Radiother Oncol. 2011 Jan;98(1):117-25.
  34. Nestle U, Kremp S, Schaefer-Schuler A, Sebastian-Welsch C, Hellwig D, Rübe C, Kirsch CM. Comparison of different methods for delineation of 18F-FDG PET–positive tissue for target volume definition in radiotherapy of patients with non–small cell lung cancer. J Nucl Med. 2005 Aug;46(8):1342-8.
  35. Zamboglou C, Thomann B, Koubar K, Bronsert P, Krauss T, Rischke HC, Sachpazidis I, Drendel V, Salman N, Reichel K, Jilg CA, Werner M, Meyer PT, Bock M, Baltas D, Grosu AL. Focal dose escalation for prostate cancer using 68 Ga-HBED-CC PSMA PET/CT and MRI: a planning study based on histology reference. Radiat Oncol. 2018 May 2;13(1):81.
  36. Thomas L, Kantz S, Hung A, Monaco D, Gaertner FC, Essler M, Strunk H, Laub W, Bundschuh RA. 68 Ga-PSMA-PET/CT imaging of localized primary prostate cancer patients for intensity modulated radiation therapy treatment planning with integrated boost. Eur J Nucl Med Mol Imaging. 2018 Jul;45(7):1170-1178.
  37. Nishioka T, Shiga T, Shirato H, Tsukamoto E, Tsuchiya K, Kato T, Ohmori K, Yamazaki A, Aoyama H, Hashimoto S, Chang TC, Miyasaka K. Image fusion between 18FDG-PET and MRI/CT for radiotherapy planning of oropharyngeal and nasopharyngeal carcinomas. Int J Radiat Oncol Biol Phys. 2002 Jul 15;53(4):1051-7.
  38. Schwartz DL, Ford EC, Rajendran J, Yueh B, Coltrera MD, Virgin J, Anzai Y, Haynor D, Lewellen B, Mattes D, Kinahan P, Meyer J, Phillips M, Leblanc M, Krohn K, Eary J, Laramore GE. FDG‐PET/CT–guided intensity modulated head and neck radiotherapy: A pilot investigation. Head Neck. 2005 Jun;27(6):478-87.
  39. Brianzoni E, Rossi G, Ancidei S, Berbellini A, Capoccetti F, Cidda C, D'Avenia P, Fattori S, Montini GC, Valentini G, Proietti A, Algranati C. Radiotherapy planning: PET/CT scanner performances in the definition of gross tumour volume and clinical target volume. Eur J Nucl Med Mol Imaging. 2005 Dec;32(12):1392-9.
  40. Giraud P, Grahek D, Montravers F, Carette M-F, Deniaud-Alexandre E, Julia F, Rosenwald JC, Cosset JM, Talbot JN, Housset M, Touboul E. CT and 18F-deoxyglucose (FDG) image fusion for optimization of conformal radiotherapy of lung cancers. Int J Radiat Oncol Biol Phys. 2001;49(5):1249-1257.