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EJNMMI Research
Published in: EJNMMI Research 1/2020

Open Access 01-12-2020 | Prostate Cancer | Original research

Day-to-day variability of [68Ga]Ga-PSMA-11 accumulation in primary prostate cancer: effects on tracer uptake and visual interpretation

Authors: Judith olde Heuvel, Berlinda J. de Wit-van der Veen, Maarten L. Donswijk, Cornelis H. Slump, Marcel P. M. Stokkel

Published in: EJNMMI Research | Issue 1/2020

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Abstract

Purpose

Prostate-specific membrane antigen (PSMA) agents, such as [68Ga]Ga-PSMA-11, have an unprecedented accuracy in staging prostate cancer (PCa) and detecting disease recurrence. PSMA PET/CT may also be used for response monitoring by displaying molecular changes, instead of morphological changes alone. However, there are still limited data available on the variability in biodistribution and intra-prostatic uptake of PSMA targeting radiotracers. Therefore, the aim of this study was to assess the repeatability of [68Ga]Ga-PSMA-11 uptake in primary PCa patients in a 4-week interval.

Methods

Twenty-four primary PCa patients were prospectively included, who already were scheduled for [68Ga]Ga-PSMA-11 PET/CT scan on clinical indication (≥ cT3, Gleason score ≥ 7 or PSA ≥ 20 ng/mL). These patients received two [68Ga]Ga-PSMA-11 PET/CT scans with a 4-week interval. No treatment was started in between the scans. Semiquantitative measurements (SULmax, SULmean, and SULpeak) were determined in the prostate tumor, normal tissues, and blood pool. The repeatability coefficient of every region was determined. All scans were visually analyzed by two nuclear medicine physicians.

Results

Within-subject coefficient of variation of [68Ga]Ga-PSMA-11 uptake between the two scans was on average 10% in the prostate tumor, normal tissues (liver, kidney, parotid), and blood pool. The repeatability coefficient of the prostate tumor was 18% for SULpeak and 22% for SULmax. Lesion uptake was visually different in 5 patients, though not clinically relevant.

Conclusion

Results of test-retest [68Ga]Ga-PSMA-11 PET/CT scans in a 4-week interval show that [68Ga]Ga-PSMA-11 uptake is repeatable, with a clinical irrelevant variation in tumor and physiological distribution. Based on the presented repeatable uptake, [68Ga]Ga-PSMA-11 PET/CT scans can potentially be used for disease surveillance and therapy response monitoring. Changes in uptake larger than the RC are therefore likely to reflect actual biological changes in PSMA expression.
Trial registration NL8263 at Trialregister.nl retrospectively registered on 03-01-2020. https://​www.​trialregister.​nl/​trial/​8263
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Literature
1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. PubMed
2.
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. CrossRefPubMed
3.
Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology. 1998;52:637–40. CrossRefPubMed
4.
Maurer T, Weirich G, Schottelius M, Weineisen M, Frisch B, Okur A, et al. Prostate-specific membrane antigen–radioguided surgery for metastatic lymph nodes in prostate cancer. Eur Urol. 2015;68:530–4. CrossRefPubMed
5.
Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, et al. Sensitivity, specificity, and predictors of positive 68Ga–prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis. Eur Urol. 2016;70:926–37. CrossRefPubMed
6.
Hofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet. 2020;395:1208–16. CrossRefPubMed
7.
Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, et al. Diagnostic efficacy of68Gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol. 2016;195:1436–42. CrossRefPubMed
8.
Herlemann A, Wenter V, Kretschmer A, Thierfelder KM, Bartenstein P, Faber C, et al. 68Ga-PSMA positron emission tomography/computed tomography provides accurate staging of lymph node regions prior to lymph node dissection in patients with prostate cancer. Eur Urol. 2016;70:553–7. CrossRefPubMed
9.
Corfield J, Perera M, Bolton D, Lawrentschuk N. 68Ga-prostate specific membrane antigen (PSMA) positron emission tomography (PET) for primary staging of high-risk prostate cancer: a systematic review. World J Urol. 2018;36:519–27. CrossRefPubMed
10.
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;50:122S-150S. CrossRefPubMed
11.
Fendler WP, Eiber M, Beheshti M, Bomanji J, Ceci F, Cho S, et al. 68Ga-PSMA PET/CT: joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2017;44:1014–24. CrossRefPubMed
12.
Schmidkonz C, Cordes M, Schmidt D, Bäuerle T, Goetz TI, Beck M, et al. 68Ga-PSMA-11 PET/CT-derived metabolic parameters for determination of whole-body tumor burden and treatment response in prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:1862–72. CrossRefPubMed
13.
Gupta M, Choudhury PS, Rawal S, Goel HC, Rao SA. Evaluation of RECIST, PERCIST, EORTC, and MDA criteria for assessing treatment response with Ga68-PSMA PET-CT in metastatic prostate cancer patient with biochemical progression: a comparative study. Nucl Med Mol Imaging. 2018;52:420–9. CrossRefPubMedPubMedCentral
14.
15.
16.
Liu C, Liu T, Zhang N, Liu Y, Li N, Du P, et al. 68Ga-PSMA-617 PET/CT: a promising new technique for predicting risk stratification and metastatic risk of prostate cancer patients. Eur J Nucl Med Mol Imaging Germany. 2018;45:1852–61. CrossRef
17.
Gafita A, Calais J, Franz C, Rauscher I, Wang H, Roberstson A, et al. Evaluation of SUV normalized by lean body mass (SUL) in 68Ga-PSMA11 PET/CT: a bi-centric analysis. EJNMMI Res. 2019;9:9–14. CrossRef
18.
James WPT, Waterlow JC. Research on obesity: a report of the DHSS/MRC group. Richmond: HM Stationery Office; 1976.
19.
Jansen BHE, Yaqub M, Voortman J, Cysouw MCF, Windhorst AD, Schuit RC, et al. Simplified methods for quantification of 18 F-DCFPyL uptake in patients with prostate cancer. J Nucl Med. 2019;60:1730–5. CrossRefPubMed
20.
Bland JM, Altman D. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;327:307–10. CrossRef
21.
22.
Ferreira G, Iravani A, Hofman MS, Hicks RJ. Intra-individual comparison of 68Ga-PSMA-11 and 18F-DCFPyL normal-organ biodistribution. Cancer Imaging. 2019;19:23. CrossRefPubMedPubMedCentral
23.
Giesel FL, Hadaschik B, Cardinale J, Radtke J, Vinsensia M, Lehnert W, et al. F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients. Eur J Nucl Med Mol Imaging. 2017;44:678–88. CrossRefPubMed
24.
O’Keefe DS, Bacich DJ, Huang SS, Heston WDW. A Perspective on the evolving story of PSMA biology, PSMA-based imaging, and endoradiotherapeutic strategies. J Nucl Med. 2018;59:1007–13. CrossRefPubMedPubMedCentral
25.
Kabasakal L, Demirci E, Ocak M, Akyel R, Nematyazar J, Aygun A, et al. Evaluation of PSMA PET/CT imaging using a 68Ga-HBED-CC ligand in patients with prostate cancer and the value of early pelvic imaging. Nucl Med Commun Engl. 2015;36:582–7. CrossRef
26.
Afshar-Oromieh A, Sattler LP, Mier W, Hadaschik BA, Debus J, Holland-Letz T, et al. The clinical impact of additional late PET/CT imaging with 68Ga-PSMA-11 (HBED-CC) in the diagnosis of prostate cancer. J Nucl Med. 2017;58:750–5. CrossRefPubMed
27.
Afshar-Oromieh A, Hetzheim H, Kübler W, Kratochwil C, Giesel FL, Hope TA, et al. Radiation dosimetry of 68Ga-PSMA-11 (HBED-CC) and preliminary evaluation of optimal imaging timing. Eur J Nucl Med Mol Imaging. 2016;43:1611–20. CrossRefPubMed
28.
Li X, Rowe SP, Leal JP, Gorin MA, Allaf ME, Ross AE, et al. Semiquantitative parameters in PSMA-targeted PET imaging with 18 F-DCFPyL: variability in normal-organ uptake. J Nucl Med US. 2017;58:942–6. CrossRef
29.
Boellaard R, Delgado-Bolton R, Oyen WJG, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2014;42:328–54. CrossRefPubMedPubMedCentral
30.
Lückerath K, Stuparu AD, Wei L, Kim W, Radu CG, Mona CE, et al. Detection threshold and reproducibility of 68 Ga-PSMA11 PET/CT in a mouse model of prostate cancer. J Nucl Med. 2018;59:1392–7. CrossRefPubMedPubMedCentral
31.
Sahakyan K, Li X, Lodge MA, Werner RA, Bundschuh RA, Bundschuh L, et al. Semiquantitative parameters in PSMA-targeted PET imaging with [18F]DCFPyL: intrapatient and interpatient variability of normal organ uptake. Mol Imaging Biol. 2020;22:181–9. CrossRefPubMedPubMedCentral
32.
Beauregard J-M, Hofman MS, Kong G, Hicks RJ. The tumour sink effect on the biodistribution of 68Ga-DOTA-octreotate: implications for peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging. 2012;39:50–6. CrossRefPubMed
33.
Evans MJ, Smith-Jones PM, Wongvipat J, Navarro V, Kim S, Bander NH, et al. Noninvasive measurement of androgen receptor signaling with a positron-emitting radiopharmaceutical that targets prostate-specific membrane antigen. Proc Natl Acad Sci. 2011;108:9578–82. CrossRefPubMedPubMedCentral
34.
Meller B, Bremmer F, Sahlmann CO, Hijazi S, Bouter C, Trojan L, et al. Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy. EJNMMI Res. 2015;5:66. CrossRefPubMedPubMedCentral
35.
Emmett L, Yin C, Crumbaker M, Hruby G, Kneebone A, Epstein R, et al. Rapid modulation of PSMA expression by androgen deprivation: serial 68 Ga-PSMA-11 PET in men with hormone-sensitive and castrate-resistant prostate cancer commencing androgen blockade. J Nucl Med. 2019;60:950–4. CrossRefPubMed
36.
Wright GL, Haley C, Beckett M L, Schellhammer PF. Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. Urol Oncol Semin Orig Investig 1995;1:18–28.
37.
Hillier SM, Kern AM, Maresca KP, Marquis JC, Eckelman WC, Joyal JL, et al. 123I-MIP-1072, a small-molecule inhibitor of prostate-specific membrane antigen, is effective at monitoring tumor response to taxane therapy. J Nucl Med. 2011;52:1087–93. CrossRefPubMed
Metadata
Title
Day-to-day variability of [68Ga]Ga-PSMA-11 accumulation in primary prostate cancer: effects on tracer uptake and visual interpretation
Authors
Judith olde Heuvel
Berlinda J. de Wit-van der Veen
Maarten L. Donswijk
Cornelis H. Slump
Marcel P. M. Stokkel
Publication date
01-12-2020
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2020
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-020-00708-z

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