SPECT-CT Imaging with [99mTc]PSMA-T4 in patients with Recurrent Prostate Cancer
Abstract
Background: Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein with a large extracellular domain with overexpression of the prostatic tumour cells. Several small molecules of PSMA ligands of inhibitors binding to the active site of PSMA were developed. [99mTc]Tc-PSMA-T4 is a new radiopharmaceutical (Polatom) for imaging loco-regional metastases and/or local relapse in patients with prostate cancer.
The purpose of this work was to evaluate the clinical application of SPECT-CT imaging with [99mTc]Tc-PSMA-T4 in patients with recurrent prostate cancer.
Material and methods: Thirty-six patients with prostate cancer, aged 60–80 years with biochemical relapse of PSA (ranged from 0.1 to 73 ng/mL) were included. Three patients were studied after tru-cut biopsy, hormonal and cytoreductive radiotherapy and 33 patients out of 36 — after radical treatment (total prostatectomy or definitive radiotherapy of the tumour). All of them underwent whole-body imaging examinations with subsequent target SPECT-CT studies of the pelvis, abdomen and/or chest, 1–3 hrs post i.v. administration of [99mTc]Tc-PSMA-T4. The average activity dose was 6.3 MBq/kg in a man of 70 kg. A Dual-head SPECT-CT gamma camera with a low dose CT scan (Symbia T2, Siemens) was used. The images were interpreted based on all other clinical and radiological data. Follow-up could be conducted in 11/36 patients during that period.
Results: Normal biodistribution of the radiopharmaceutical with high activity background was observed in the liver, spleen, kidneys, lacrimal and salivary glands, bowels and urinary bladder. Positive imaging for local relapse in the prostate bad was imaged in 21 patients, lymph node metastases — in 16 cases, bone lesions — in 10 cases, pulmonary metastases – in 2 cases, hepatic lesions were visualised in one of them and in another — adrenal suprarenal metastasis with intensive tracer uptake significant for overexpression of PSMA. There was a suspicion for local recurrences in 4 patients with negative MRT studies who were followed up. In 3 cases, previously treated bone metastases were partially negative without tracer uptake, only some progressive bone lesions were positive. Five patients were with negative results. Sensitivity was 84.37% (27/32), specificity — 100% (4/4) and accuracy — 86.11% (31/36).
Conclusions: In conclusion SPECT-CT imaging with [99mTc]Tc-PSMA-T4 could be applied in patients with prostate cancer for the diagnosis of recurrent disease to determine personalized treatment for each patient. Specific uptake of this tracer, depicted by SPECT-CT images has clinical importance of identifying and assessing PSMA expression before consideration of Radio Ligand Therapy (RLT) with [177Lu]Lu-PSMA. SPECT-CT imaging with [99mTc]PSMA is promising and reliable nuclear medicine approach to monitoring therapeutic effect after treatment and for restaging of the disease.
Keywords: recurrent prostate cancerPSMA[99mTc]Tc-PSMA-T4SPECT-CT
References
- Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018; 103: 356–387.
- European Cancer Information System-ECIS, European Commission 2018. https://ecis.jrc.ec.europa.eu/ (12.03.2019).
- Kelloff GJ, Choyke P, Coffey DS, et al. Prostate Cancer Imaging Working Group. Challenges in clinical prostate cancer: role of imaging. AJR Am J Roentgenol. 2009; 192(6): 1455–1470.
- Engelbrecht MR, Jager GJ, Laheij RJ, et al. Local staging of prostate cancer using magnetic resonance imaging: a meta-analysis. Eur Radiol. 2002; 12(9): 2294–2302.
- Hillier SM, Maresca KP, Lu G, et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen for molecular imaging of prostate cancer. J Nucl Med. 2013; 54(8): 1369–1376.
- von Eyben FE, Picchio M, von Eyben R, et al. Ga-Labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography for Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol Focus. 2018; 4(5): 686–693.
- Hupe MC, Philippi C, Roth D, et al. Expression of Prostate-Specific Membrane Antigen (PSMA) on Biopsies Is an Independent Risk Stratifier of Prostate Cancer Patients at Time of Initial Diagnosis. Front Oncol. 2018; 8: 623.
- Oliveira JM, Gomes C, Faria DB, et al. Ga-prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Prostate Cancer Imaging: A Narrative Literature Review. World J Nucl Med. 2017; 16(1): 3–7.
- Kratochwil C, Giesel FL, Stefanova M, et al. PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617. J Nucl Med. 2016; 57(8): 1170–1176.
- Jones W, Griffiths K, Barata PC, et al. PSMA Theranostics: Review of the Current Status of PSMA-Targeted Imaging and Radioligand Therapy. Cancers (Basel). 2020; 12(6).
- Schwarzenboeck SM, Rauscher I, Bluemel C, et al. PSMA Ligands for PET Imaging of Prostate Cancer. J Nucl Med. 2017; 58(10): 1545–1552.
- Beheshti M, Manafi-Farid R, Geinitz H, et al. Multiphasic Ga-PSMA PET/CT in the Detection of Early Recurrence in Prostate Cancer Patients with a PSA Level of Less Than 1 ng/mL: A Prospective Study of 135 Patients. J Nucl Med. 2020; 61(10): 1484–1490.
- Krimphove MJ, Theissen LH, Cole AP, et al. Performance and Impact of Prostate Specific Membrane Antigen-Based Diagnostics in the Management of Men with Biochemical Recurrence of Prostate Cancer and its Role in Salvage Lymph Node Dissection. World J Mens Health. 2020; 38(1): 32–47.
- Mariani G, Bruselli L, Kuwert T, et al. A review on the clinical uses of SPECT/CT. Eur J Nucl Med Mol Imaging. 2010; 37(10): 1959–1985.
- Schmidkonz C, Hollweg C, Beck M, et al. Tc-MIP-1404-SPECT/CT for the detection of PSMA-positive lesions in 225 patients with biochemical recurrence of prostate cancer. Prostate. 2018; 78(1): 54–63.
- Liu C, Zhu Y, Su H, et al. Relationship between PSA kinetics and Tc-99m HYNIC PSMA SPECT/CT detection rates of biochemical recurrence in patients with prostate cancer after radical prostatectomy. Prostate. 2018; 78(16): 1215–1221.
- Albalooshi B, Al Sharhan M, Bagheri F, et al. Direct comparison of Tc-PSMA SPECT/CT and Ga-PSMA PET/CT in patients with prostate cancer. Asia Ocean J Nucl Med Biol. 2020; 8(1): 1–7.
- Goffin KE, Joniau S, Tenke P, et al. Phase 2 Study of Tc-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(9): 1408–1413.
- Trabulsi EJ, Rumble RB, Jadvar H, et al. Optimum Imaging Strategies for Advanced Prostate Cancer: ASCO Guideline. J Clin Oncol. 2020; 38(17): 1963–1996.
- Maurer T, Robu S, Schottelius M, et al. Technetium-based Prostate-specific Membrane Antigen-radioguided Surgery in Recurrent Prostate Cancer. Eur Urol. 2019; 75(4): 659–666.
- Su HC, Zhu Y, Hu SL, et al. The Value of Tc-PSMA SPECT/CT-Guided Surgery for Identifying and Locating Lymph Node Metastasis in Prostate Cancer Patients. Ann Surg Oncol. 2019; 26(2): 653–659.