Quantitative evaluation by SPECT/CT of Radionuclide Therapy with Radium-223 Chloride of Bone Metastases in Metastatic Castration-resistant Prostate Cancer

   Evaluation of the effectiveness of bone metastasis therapy is an urgent problem for patients with prostate cancer, mainly due to the relationship between bone metastases, survival and quality of life, which directly depends on the correct interpretation of the results of treatment response. It is known that some patients may experience a multidirectional therapeutic effect in the form of a positive response of some bone metastases and the progression of others. In addition, there are now many new therapeutics with different action profiles and often extremely expensive, so it is important to quickly recognize whether true or pseudo-disease progression is occurring, and this is more evident in patients enrolled in clinical trials with fixed protocols, often requiring radiographic assessment early after the start of treatment. Therefore, the use of additional imaging modalities in clinical practice along with PSA assessment may help improve early prediction of outcome and monitor response to therapy in patients with metastatic CRPC, optimizing the use of this costly treatment.

1. Negoita S., Feuer E. J., Mariotto A. Annual Report to the Nation on the Status of Cancer, part II: Recent changes in prostate cancer trends and disease characteristics. Cancer. 2018; 124 (13): 2801-14. DOI: 10.1002/cncr.31549.

2. Rizzini E. L., Dionisi V., Ghedini P. Clinical aspects of mCRPC management in patients treated with radium-223. Sci Rep. 2020; 10 (1): 6681. DOI: 10.1038/s41598-020-63302-2.

3. Siegel R. L., Miller K. D., Fuchs H. E., Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021; 71 (1): 7-33. DOI: 10.3322/caac.21654.

4. Hoskin P., Sartor O., O’Sullivan J. M., et al. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. Lancet Oncol. 2014 Nov; 15 (12): 1397-406. DOI: 10.1016/S1470-2045(14)70474-7.

5. Heidenreich A., Bastian P. J., Bellmunt J., et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014; 65 (2): 467–79. DOI: 10.1016/j.eururo.2013.11.002.

6. Attard G., Borre M., Gurney H., Loriot Y., Andresen-Daniil C., Kalleda R., Pham T., Taplin M. E.; PLATO collaborators. Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment. J Clin Oncol. 2018 Sep 1; 36 (25): 2639-46. DOI: 10.1200/JCO.2018.77.9827.

7. Le Vee A., Lin C. Y., Posadas E., et al. Clinical Utility of Olaparib in the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Review of Current Evidence and Patient Selection. Onco Targets Ther. 2021; 14: 4819-32. DOI: 10.2147/OTT.S315170.

8. Parker C., Nilsson S., Heinrich D. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23. DOI: 10.1056/NEJMoa1213755.

9. Suominen M. I., Fagerlund K. M., Rissanen J. P., et al. Radium-223 Inhibits Osseous Prostate Cancer Growth by Dual Targeting of Cancer Cells and Bone Microenvironment in Mouse Models. Clin Cancer Res. 2017; 23 (15): 4335-46. DOI: 10.1158/1078-0432.CCR-16-2955.

10. Nilsson S. Radionuclide therapies in prostate cancer: integrating radium-223 in the treatment of patients with metastatic castration-resistant prostate cancer. Curr Oncol Rep. 2016; 18: 14.

11. Parker C., Gillessen S., Heidenreich A., Horwich A. Cancer of the prostate: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015; 26 (Suppl 5): v69–v77. DOI: 10.1093/annonc/mdv222.

12. Sartor O., de Bono J., Chi K. N., Fizazi K., et al; VISION Investigators. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021; 385 (12): 1091-103. DOI: 10.1056/NEJMoa2107322

13. Ozdemir S., Ersay A. R., Koc Ozturk F., et al. Predictive value of standard serum markers for bone metastases in prostate cancer. Afr J Urol. 2021; 27: 69. DOI: 10.1186/s12301-021-00170-w

14. Jung J. H., Hong C. M., Jo I., et al. Reliability of Alkaline Phosphatase for Differentiating Flare Phenomenon from Disease Progression with Bone Scintigraphy. Cancers (Basel). 2022; 14 (1): 254. DOI: 10.3390/cancers14010254

15. Sartor O., Coleman R. E., Nilsson S., et al. An exploratory analysis of alkaline phosphatase, lactate dehydrogenase, and prostate-specific antigen dynamics in the phase 3 ALSYMPCA trial with radium-223. Ann Oncol. 2017; 28 (5): 1090-97. DOI: 10.1093/annonc/mdx044.

16. Wood S. L., Brown J. E. Personal Medicine and Bone Metastases: Biomarkers, Micro-RNAs and Bone Metastases. Cancers (Basel). 2020; 12 (8): 2109. DOI: 10.3390/cancers12082109

17. Клинические рекомендации: рак предстательной железы. Одобрено Научно-практическим Советом Минздрава РФ. – 2020 [Clinical guidelines: prostate cancer. Approved by the Scientific and Practical Council of the Ministry of Health of the Russian Federation, 2020 (In Russian)].

18. Heck M. M. Prospective comparison of computed tomography, diffusionweighted magnetic resonance imaging and [ 11 C]choline positron emission tomography / computed tomography for preoperative lymph node staging in prostate cancer patients. Eur J Nucl Med Mol Imaging. 2014; 41: 694.

19. Mingels C., Bohn K. P., Rominger A., Afshar-Oromieh A., Alberts I. Diagnostic accuracy of [18 F] PSMA-1007 PET/CT in biochemical recurrence of prostate cancer. Eur J Nucl Med Mol Imaging. 2022 Jun; 49 (7): 2436-44. DOI: 10.1007/s00259-022-05693-0.

20. Wang X., Wen Q., Zhang H., Ji B. Head-to-Head Comparison of 68 Ga-PSMA-11 PET/CT and Multiparametric MRI for Pelvic Lymph Node Staging Prior to Radical Prostatectomy in Patients With Intermediate to High-Risk Prostate Cancer: A Meta-Analysis. Front Oncol. 2021 Oct 20; 11: 737989. DOI: 10.3389/fonc.2021.737989

21. FDA Approves Pluvicto/Locametz for Metastatic Castration-Resistant Prostate Cancer. J Nucl Med. 2022; 63 (5): 13N. PMID: 35487569.

22. Kapsoritakis N., Stathaki M., Bourogianni O. Clinical impact of targeted single-photon emission computed tomography / computed tomography (SPECT/CT) bone scintigraphy on the assessment of bone metastasis in cancer patients. Nucl Med Commun. 202; 42: 1202–8. DOI: 10.1097/MNM.0000000000001455

23. Ross J. C., Vilić D., Sanderson T., Vöö S., Dickson J. Does quantification have a role to play in the future of bone SPECT? Eur J Hybrid Imaging. 2019; 3 (1): 8. DOI: 10.1186/s41824-019-0054-6.

24. Dickson J. C. Quantitative SPECT: a survey of current practice in the UK Nuclear Medicine Community. Nucl Med Commun. 2019 Oct; 40 (10): 986-94. DOI: 10.1097/MNM.0000000000001059.

25. Anand A., Trägårdh E., Edenbrandt L. Assessing Radiographic Response to 223 Ra with an Automated Bone Scan Index in Metastatic Castration-Resistant Prostate Cancer Patients. J Nucl Med. 2020; 61 (5): 671-5. DOI: 10.2967/jnumed.119.231100.

26. Reza M., Wirth M., Tammela T., Cicalese V. Automated Bone Scan Index as an Imaging Biomarker to Predict Overall Survival in the Zometa European Study / SPCG11. Eur Urol Oncol. 2021; 4 (1): 49-55. DOI: 10.1016/j.euo.2019.05.002.

27. Abikhzer G., Srour S., Keidar Z., Bar-Shalom R. Added value of SPECT/CT in the evaluation of benign bone diseases of the appendicular skeleton. Clin Nuclear Med. 2016; 41: e195. DOI: 10.1097/RLU.0000000000001042.

28. Guezennec C., Keromnes N., Robin P., Abgral R. Incremental diagnostic utility of systematic double-bed SPECT/CT for bone scintigraphy in initial staging of cancer patients. Cancer Imaging. 2017; 17: 16. DOI: 10.1186/s40644-017-0118-4.

29. Zeintl J., Vija A. H., Yahil A., Hornegger J., Kuwert T. Quantitative accuracy of clinical 99m Tc SPECT / CT using ordered-subset expectation maximization with 3-dimensional resolution recovery, attenuation, and scatter correction. J Nucl Med. 2010; 51: 921-8. DOI: 10.2967/jnumed.109.071571.

30. Umeda T., Koizumi M., Fukai S. Evaluation of bone metastatic burden by bone SPECT / CT in metastatic prostate cancer patients: defining threshold value for total bone uptake and assessment in radium-223 treated patients. Ann Nucl Med. 2018; 32 (2): 105-13. DOI:10.1007/s12149-017-1224-x.

31. Kuji I., Yamane T., Seto A., Yasumizu Y., Shirotake S., Oyama M. Skeletal standardized uptake values obtained by quantitative SPECT/CT as an osteoblastic biomarker for the discrimination of active bone metastasis in prostate cancer. Eur J Hybrid Imaging. 2017;1 (1): 2. DOI: 10.1186/s41824-017-0006-y.

32. Tabotta F., Jreige, M., Schaefer N. Quantitative bone SPECT / CT: high specificity for identification of prostate cancer bone metastases. BMC Musculoskelet Disord. 2019; 20: 619. DOI: 10.1186/s12891-019-3001-6.

33. Chirindel A., Alluri K. C., Tahari A. K. Liver standardized uptake value corrected for lean body mass at FDG PET / CT: effect of FDG uptake time. Clin Nucl Med. 2015; 40: e17-e22. DOI: 10.1097/RLU.0000000000000446.

34. Wang Ruifeng, Duan Xiaoyi, Shen Cong, et al. A retrospective study of SPECT / CT scans using SUV measurement of the normal pelvis with Tc-99m methylene diphosphonate. J X-Ray Science and Technology. 2018; 26 (6): 895-908. DOI: 10.3233/XST-180391.

35. Fukai S., Daisaki H., Umeda T., et al. Impact of patient body habitus on image quality and quantitative value in bone SPECT / CT. Ann Nucl Med. 2022 May 11. DOI: 10.1007/s12149-022-01746-4.

36. Sher A., Lacoeuille F., Fosse P., Vervueren L. For avid glucose tumors, the SUV peak is the most reliable parameter for [18 F]FDG-PET / CT quantification, regardless of acquisition time. EJNMMI Res. 2016; 6: 21. DOI: 10.1186/s13550-016-0177-8.

37. Kaneta T., Ogawa M., Daisaki H., Nawata S., Yoshida K., Inoue T. SUV measurement of normal vertebrae using SPECT / CT with Tc-99m methylene diphosphonate. Am J Nucl Med Mol Imaging. 2016; 6: 262-8.

38. Buchbender C., Hartung-Knemeyer V., Forsting M., Antoch G., Heusner T. A. Positron emission tomography (PET) attenuation correction artefacts in PET / CT and PET / MRI. Br J Radiol. 2013; 86 (1025): 20120570. DOI: 10.1259/bjr.20120570.

39. Ljungberg M., Pretorius P. H. SPECT/CT: an update on technological developments and clinical applications. Br J Radiol. 2018; 91 (1081): 20160402. DOI: 10.1259/bjr.20160402.

40. Sanderson T., Gear J. I., Murray I., Flux G. The impact of background ratios in calibration phantoms on the accuracy of dosimetry for Y-90 DOTATATE. Nucl Med Commun. 2015; 36 (5): 512-47. DOI: 10.1097/MNM.0000000000000310.

41. O’Mahoney E., Murray I. Evaluation of a matched filter resolution recovery reconstruction algorithm for SPECT-CT imaging. Nucl Med Commun. 2013; 34 (3): 240-8. DOI: 10.1097/MNM.0b013e32835ce5b5.

42. Bailey D. L., Willowson K. P. An evidence-based review of quantitative SPECT imaging and potential clinical applications. J Nucl Med. 2013; 54: 83-9. DOI: 10.2967/jnumed.112.111476.

43. Jarritt P. H., Whalley D. R., Skrypniuk J. V., Houston A. S., Fleming J. S., Cosgriff P. S. UK audit of single photon emission computed tomography reconstruction software using software generated phantoms. Nucl Med Commun. 2002; 23: 483-91. DOI: 10.1097/00006231-200205000-00009.

44. Beck M., Sanders J. C., Ritt P., Reinfelder J., Kuwert T. Longitudinal analysis of bone metabolism using SPECT / CT and 99m Tc-diphosphonopropanedicarboxylic acid: comparison of visual and quantitative analysis. EJNMMI Res. 2016; 6: 60. DOI: 10.1186/s13550-016-0217-4.

45. Nakahara T., Daisaki H., Yamamoto Y., Iimori T., Miyagawa K., Okamoto T. Use of a digital phantom developed by QIBA for harmonizing SUVs obtained from the state-of-the-art SPECT / CT systems: a multicenter study. EJNMMI Res. 2017; 7: 53. DOI: 10.1186/s13550-017-0300-5.

46. Stokke C., Gabiña P. M., Solný P. Dosimetry-based treatment planning for molecular radiotherapy: a summary of the 2017 report from the Internal Dosimetry Task Force. EJNMMI Phys. 2017; 4: 27. DOI: 10.1186/s40658-017-0194-3.

47. Iuliani M., Pantano F., Buttigliero C., et al. Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment. Oncotarget. 2015; 6: 12520-8.

48. Schreiber R. D., Old L. J. and Smyth M. J. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011; 331: 1565-70

49. Larbi A., Omoumi P., Pasoglou V., et al. Whole body MRI to assess bone involvement in prostate cancer and multiple myeloma: comparison of the diagnostic accuracies of the T 1, short tau inversion recovery (STIR), and high b-values diffusion-weighted imaging (DWI) sequences. Eur Radiol. 2019; 8: 4503-13.

50. Yu Y. S., Li W. H., Li M. H., et al. False-positive diagnosis of disease progression by magnetic resonance imaging for response assessment in prostate cancer with bone metastases: a case report and review of the pitfalls of images in the literature. Oncol Lett. 2015; 10: 3585-90.

51. Aggarwal R., Wei X., Kim W. Heterogeous flare in prostate-specific membrane antigen positron emission tomography tracer with initiation of androgen pathway blockade in metastatic prostate cancer. Eur Urol Oncol. 2018; 1: 78-82.

52. Plouznikoff N., Artigas C., Sideris S. Evaluation of PSMA expression changes on PET/CT before and after initiation of novel antiandrogen drugs (enzalutamide or abiraterone) in metastatic castration-resistant prostate cancer patients. Ann Nucl Med. 2019; 33: 945-54.

53. Messiou C., Cook G., de Souza N. M. Imaging metastatic bone disease from carcinoma of the prostate. Br J Cancer. 2009; 101: 1225-32.

54. Cook G. J., Venkitaraman R., Sohaib A. S., et al. The diagnostic utility of the flare phenomenon on bone scintigraphy in staging prostate cancer. Eur J Nucl Med Mol Imaging. 2011; 38: 7-13.

55. Messiou C., Cook G., Reid A. H., et al. The CT flare response of metastatic bone disease in prostate cancer. Acta Radiol. 2011; 52: 557-61.

56. Scher H. I., Morris M. J., Stadler W. M., et al. Prostate Cancer Clinical Trials Working Group 3. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016; 34 (12): 1402-18. DOI: 10.1200/JCO.2015.64.2702.

57. Ryan C. J., Shah S., Efstathiou E., et al. Phase II study of abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer displaying bone flare discordant with serologic response. Clin Cancer Res. 2011; 17: 4854-61.