Skip to main content
Log in

PSMA SPECT/CT with 99mTc-MIP-1404 in biochemical recurrence of prostate cancer: predictive factors and efficacy for the detection of PSMA-positive lesions at low and very-low PSA levels

  • Original Article
  • Published:
Annals of Nuclear Medicine Aims and scope Submit manuscript

Abstract

Background

The in vivo expression of the prostate-specific membrane antigen (PSMA) can be investigated using the SPECT-suitable tracer 99mTc-MIP-1404. We investigated the performance of 99mTc-MIP-1404 PSMA SPECT/CT in the detection of PSMA-positive tumor lesions in patients suffering from biochemical recurrence of prostate cancer presenting with serum levels of the prostate-specific antigen (PSA) below 1 ng/mL.

Methods

We retrospectively analyzed 99mTc-MIP-1404-SPECT/CT scans

of 50 patients (25 with low PSA levels between > 0.5 and 1 ng/mL and 25 with very low PSA levels between 0.2 and 0.5 ng/mL) that had undergone whole-body planar scintigraphy and SPECT/CT of the thorax, abdomen and pelvis 3–4 h p.i. of 691 ± 72 MBq 99mTc-MIP-1404. All datasets were evaluated for the presence and location of PSMA-positive tumor lesions, in which maximal standardized uptake values (SUVmax) were also measured. Based on the results of the quantitative evaluation as well as on biochemical and histological parameters, predictive factors for a positive 99mTc-MIP-1404 scan result were determined. The influence of 99mTc-MIP-1404 PSMA SPECT/CT on further therapy planning was assessed, based on the decision-making of the interdisciplinary tumor board.

Results

Pathological 99mTc-MIP-1404 uptake was detected in a total of 25 patients (50%). In the very low PSA subgroup, detection rates of PSMA-positive lesions suggestive of tumor recurrence were 44%, in the low-PSA subgroup 56%. Gleason scores ≥ 8 and the presence of antiandrogen deprivation therapy were further significant predictors of pathological 99mTc-MIP-1404 uptake. This was paralleled by significantly higher lesional SUVmax patients with PSA levels > 0.5 ng/mL and Gleason scores ≥ 8 compared to those without these two features. Changes in therapeutic strategy following MIP-1404 imaging were recommended by the interdisciplinary tumor board in 25/50 of patients.

Conclusion

99mTc-MIP-1404 PSMA-SPECT/CT demonstrated a high performance in detecting PSMA-positive lesions suggestive of tumor recurrence in patients with biochemical recurrence of prostate cancer and low and very low serum PSA levels. Results from MIP-1404 PSMA SPECT/CT have therapeutic impact in one-half of the patients examined by this technology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Sokoloff R, Norton K, Gasior C, Marker K, Grauer L. A dual-monoclonal sandwich assay for prostate-specific membrane antigen: levels in tissues, seminal fluid and urine. Prostate. 2000;43:150–7.

    Article  CAS  Google Scholar 

  2. Silver DA, Pellicer I, Fair WR, Heston W, 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 

  3. Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, 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  Google Scholar 

  4. Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, et al. Diagnostic efficacy of 68 gallium-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;195:1436–43.

    Article  Google Scholar 

  5. Pyka T, Okamoto S, Dahlbender M, Tauber R, Retz M, Heck M, et al. Comparison of bone scintigraphy and 68Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:2114–211.

    Article  CAS  Google Scholar 

  6. Maurer T, Eiber M, Schwaiger M, Gschwend JE. Current use of PSMA-PET in prostate cancer management. Nat Rev Urol. 2016;13:226.

    Article  CAS  Google Scholar 

  7. Calais J, Fendler WP, Eiber M, Gartmann J, Chu F-I, Nickols NG, et al. Impact of 68Ga-PSMA-11 PET/CT on the management of prostate cancer patients with biochemical recurrence. J Nucl Med. 2018;59:434–41.

    Article  Google Scholar 

  8. Afaq A, Alahmed S, Chen S-H, Lengana T, Haroon A, Payne H, et al. Impact of 68Ga-prostate-specific membrane antigen PET/CT on prostate cancer management. J Nucl Med. 2018;59:89–92.

    Article  CAS  Google Scholar 

  9. Albisinni S, Artigas C, Aoun F, Biaou I, Grosman J, Gil T, et al. Clinical impact of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer with rising prostate-specific antigen after treatment with curative intent: preliminary analysis of a multidisciplinary approach. BJU Int. 2017;120:197–203.

    Article  CAS  Google Scholar 

  10. Hillier SM, Maresca KP, Lu G, Merkin RD, Marquis JC, Zimmerman CN, et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen for molecular imaging of prostate cancer. J Nucl Med. 2013;54:1369–76.

    Article  CAS  Google Scholar 

  11. Vallabhajosula S, Nikolopoulou A, Babich JW, Osborne JR, Tagawa ST, Lipai I, et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen: pharmacokinetics and biodistribution studies in healthy subjects and patients with metastatic prostate cancer. J Nucl Med. 2014;55:1791–8.

    Article  CAS  Google Scholar 

  12. Reinfelder J, Kuwert T, Beck M, Sanders JC, Ritt P, Schmidkonz C, et al. First experience with SPECT/CT using a 99mTc-labeled inhibitor for prostate-specific membrane antigen in patients with biochemical recurrence of prostate cancer. Clin Nucl Med. 2017;42:26–33.

    Article  Google Scholar 

  13. Schmidkonz C, Hollweg C, Beck M, Reinfelder J, Goetz TI, Sanders JC, et al. 99mTc-MIP-1404-SPECT/CT for the detection of PSMA-positive lesions in 225 patients with biochemical recurrence of prostate cancer. Prostate. 2018;78:54–63.

    Article  CAS  Google Scholar 

  14. Goffin KE, Joniau S, Tenke P, Slawin K, Klein EA, Stambler N, et al. Phase 2 study of 99mTc-Trofolastat SPECT/CT to identify and localize prostate cancer in intermediate-and high-risk patients undergoing radical prostatectomy and extended pelvic LN dissection. J Nucl Med. 2017;58:1408–13.

    Article  CAS  Google Scholar 

  15. Schmidkonz C, Cordes M, Beck M, Goetz TI, Schmidt D, Prante O, et al. SPECT/CT with the PSMA ligand 99mTc-MIP-1404 for whole-body primary staging of patients with prostate cancer. Clin Nucl Med. 2018;43:225–31.

    Article  Google Scholar 

  16. Schmidkonz C, Cordes M, Beck M, Goetz TI, Schmidt D, Prante O, et al. Assessment of treatment response by 99mTc-MIP-1404 SPECT/CT: a pilot study in patients with metastatic prostate cancer. Clin Nucl Med. 2018;43:e250–e258258.

    Article  Google Scholar 

  17. Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, et al. The diagnostic value of PET/CT imaging with the 68Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:197–209.

    Article  CAS  Google Scholar 

  18. 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.

    Article  Google Scholar 

  19. King CR. The timing of salvage radiotherapy after radical prostatectomy: a systematic review. Int J Radiat Oncol Biol Phys. 2012;84:104–11.

    Article  Google Scholar 

  20. Ohri N, Dicker AP, Trabulsi EJ, Showalter TN. Can early implementation of salvage radiotherapy for prostate cancer improve the therapeutic ratio? A systematic review and regression meta-analysis with radiobiological modelling. Eur J Cancer. 2012;48:837–44.

    Article  Google Scholar 

  21. Thompson IM, Valicenti RK, Albertsen P, Davis BJ, Goldenberg SL, Hahn C, et al. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO guideline. J Urol. 2013;190:441–9.

    Article  Google Scholar 

  22. Association WM. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310:2191.

    Article  Google Scholar 

  23. Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent—update 2013. Eur Urol. 2014;65:124–37.

    Article  Google Scholar 

  24. Lu G, Maresca KP, Hillier SM, Zimmerman CN, Eckelman WC, Joyal JL, et al. Synthesis and SAR of 99m Tc/Re-labeled small molecule prostate specific membrane antigen inhibitors with novel polar chelates. Bioorg Med Chem Lett. 2013;23:1557–633.

    Article  CAS  Google Scholar 

  25. Zeintl J, Vija AH, Yahil A, Hornegger J, Kuwert T. Quantitative accuracy of clinical 99mTc SPECT/CT using ordered-subset expectation maximization with 3-dimensional resolution recovery, attenuation, and scatter correction. J Nucl Med. 2010;51:921–8.

    Article  Google Scholar 

  26. Rauscher I, Düwel C, Haller B, Rischpler C, Heck MM, Gschwend JE, et al. Efficacy, predictive factors, and prediction nomograms for 68Ga-labeled prostate-specific membrane antigen–ligand positron-emission tomography/computed tomography in early biochemical recurrent prostate cancer after radical prostatectomy. Eur Urol. 2018;73:656–61.

    Article  Google Scholar 

  27. Lawal IO, Ankrah AO, Mokgoro NP, Vorster M, Maes A, Sathekge MM. Diagnostic sensitivity of Tc-99m HYNIC PSMA SPECT/CT in prostate carcinoma: a comparative analysis with Ga-68 PSMA PET/CT. Prostate. 2017;77:1205–12.

    Article  CAS  Google Scholar 

  28. Kasperzyk JL, Finn SP, Flavin RJ, Fiorentino M, Lis RT, Hendrickson WK, et al. Prostate-specific membrane antigen protein expression in tumor tissue and risk of lethal prostate cancer. Cancer Epidemiol Prev Biomark. 2013. https://doi.org/10.1158/1055-9965.EPI-13-0668.

    Article  Google Scholar 

  29. Ross JS, Sheehan CE, Fisher HA, Kaufman RP, Kaur P, Gray K, et al. Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer. Clin Cancer Res. 2003;9:6357–62.

    CAS  PubMed  Google Scholar 

  30. Mostaghel EA, Page ST, Lin DW, Fazli L, Coleman IM, True LD, et al. Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Can Res. 2007;67:5033–41.

    Article  CAS  Google Scholar 

  31. Wright GL, Grob BM, Haley C, Grossman K, Newhall K, Petrylak D, et al. Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology. 1996;48:326–34.

    Article  Google Scholar 

  32. Roach PJ, Francis R, Emmett L, Hsiao E, Kneebone A, Hruby G, et al. The impact of 68Ga-PSMA PET/CT on management intent in prostate cancer: results of an Australian prospective multicenter study. J Nucl Med. 2017. https://doi.org/10.2967/jnumed.117.197160.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christian Schmidkonz.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed written consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schmidkonz, C., Goetz, T.I., Kuwert, T. et al. PSMA SPECT/CT with 99mTc-MIP-1404 in biochemical recurrence of prostate cancer: predictive factors and efficacy for the detection of PSMA-positive lesions at low and very-low PSA levels. Ann Nucl Med 33, 891–898 (2019). https://doi.org/10.1007/s12149-019-01400-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12149-019-01400-6

Keywords

Navigation