A pilot study of 68 Ga-PSMA-617 PET/CT imaging and 177Lu-EB-PSMA-617 radioligand therapy in patients with adenoid cystic carcinoma

Guochang Wang, Mengjiao Zhou, Jie Zang, Yuanyuan Jiang, Xiaohong Chen, Zhaohui Zhu, Xiaoyuan Chen, Guochang Wang, Mengjiao Zhou, Jie Zang, Yuanyuan Jiang, Xiaohong Chen, Zhaohui Zhu, Xiaoyuan Chen

Abstract

Background: This pilot study was designed to evaluate the diagnostic value of 68 Ga-PSMA-617 and 18F-FDG PET/CT in adenoid cystic carcinoma (ACC) and to assess the safety and therapeutic response to PSMA radioligand therapy (RLT) in ACC patients.

Methods: Thirty patients pathologically diagnosed with ACC were recruited into the cohort. Each patient underwent 68 Ga-PSMA-617 and 18F-FDG PET/CT within 1 week. The number and SUVmax of PET-positive lesions were recorded and compared. Four patients accepted RLT using 177Lu-EB-PSMA-617, in a dosage of approximately 1.85 GBq (50 mCi) per cycle for up to 3 cycles.

Results: Compared with 18F-FDG, 68 Ga-PSMA-617 revealed more PET-positive extrapulmonary tumors (157 vs. 141, P = 0.016) and higher SUVmax (8.8 ± 3.6 vs. 6.4 ± 4.2, P = 0.027). However, 68 Ga-PSMA-617 revealed less PET-positive pulmonary lesions (202 vs. 301, P < 0.001) and lower SUVmax of tumors (3.1 ± 3.0 vs. 4.2 ± 3.9, P < 0.001) than 18F-FDG. The combination of 68 Ga-PSMA-617 and 18F-FDG can detect 469 PET-positive lesions, which was superior to each alone (469 vs. 359 vs. 442, P < 0.001). Two patients achieved remarkable response after PSMA RLT, while the other two patients showed reduced tumor uptake of recurrent foci, lung and liver metastases, whereas increased SUVmax of bone metastases.

Conclusions: 68 Ga-PSMA-617 PET/CT is a valuable imaging modality for the detection of ACC and combining with 18F-FDG PET/CT will achieve a higher detection efficiency. PSMA RLT may be a promising treatment for ACC and is worth of further investigation.

Trial registration: Diagnosis of Adenoid Cystic Carcinoma on 68 Ga-PSMA-617 PET-CT and Therapy With 177Lu-EB-PSMA-617 (NCT04801264, Registered 16 March 2021, retrospectively registered). URL of registry: https://ichgcp.net/clinical-trials-registry/NCT04801264 .

Keywords: 177Lu-EB-PSMA-617; 18F-FDG PET/CT; 68 Ga-PSMA-617 PET/CT; Adenoid cystic carcinoma.

Conflict of interest statement

All authors have no competing interests to disclose.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Structural formula of PSMA-617 (A) and EB-PSMA-617 (B)
Fig. 2
Fig. 2
A 53-year-old female patient with primary ACC. Anterior maximum intensity projection (MIP) and axial 68 Ga-PSMA PET/CT (A–C) showed increased tracer uptake of the tumor in the left maxillary sinus (green arrow, SUVmax 9.8). 18F-FDG PET/CT (D–F) showed a lower uptake (blue arrow, SUVmax 6.3)
Fig. 3
Fig. 3
A 62-year-old man was diagnosed with local recurrence and distant metastases 21 months after surgical removal of a right maxillary sinus ACC. 68 Ga-PSMA PET/CT (A–E) revealed a PSMA-avid tumor in the right maxillary sinus (green arrow, SUVmax 11.2), multiple bone metastases (red arrow, SUVmax 16.2), and liver metastases (blue arrow, SUVmax 8.8). 18F-FDG PET/CT (F–J) showed negative recurrent and metastatic foci
Fig. 4
Fig. 4
A 49-year-old man was diagnosed with local recurrence and distant metastases 74 months after surgical removal of a left maxillary ACC. 68 Ga-PSMA PET/CT (A–C) showed multiple lung metastases with negligible uptake (green arrow). 18F-FDG PET/CT (D–F) revealed FDG-avid pulmonary lesions (blue arrow, SUVmax 7.1)
Fig. 5
Fig. 5
A 41-year-old female patient was diagnosed with a left frontal meningeal metastasis 20 months after surgical removal of the left lacrimal gland ACC. Pre-therapy 68 Ga-PSMA-617 PET/CT (A–C) demonstrated intense PSMA uptake of tumor (green arrow, SUVmax 7.0). 68 Ga-PSMA-617 PET/CT reexamination at 9 weeks after the 1st cycle of PSMA RLT (D–F) and 8 weeks after the 3rd cycle of PSMA RLT (G–I) revealed significantly decreased tracer uptake of tumor (red arrow, SUVmax 3.5; blue arrow, SUVmax 1.1), which reached the level of CR according to modified PERSIST criteria. However, 18F-FDG PET/CT (J–L) always exhibited no positive lesions (orange arrow)
Fig. 6
Fig. 6
A 56-year-old male patient was diagnosed with local recurrence and multiple metastases 12 months after surgical removal of nasal ACC. Pre-therapy 68 Ga-PSMA-617 (A–D) and 18F-FDG PET/CT (I–L) depicted neoplasm recurrence, multiple liver, bone, and lung metastases. 68 Ga-PSMA-617 PET/CT (E–H) and 18F-FDG PET/CT (M–P) reexamination at 8 weeks after the 1st cycle of PSMA RLT revealed the decreased SUVmax of lung metastases (red arrow) and liver metastases (blue arrow); and CT showed liquefied necrosis occurred inside the lung nodule (red arrow). The uptakes of bone metastases (yellow arrow), however, were significantly increased

References

    1. Coca-Pelaz A, Rodrigo JP, Bradley PJ, Vander Poorten V, Triantafyllou A, Hunt JL, et al. Adenoid cystic carcinoma of the head and neck–an update. Oral Oncol. 2015;51:652–661. doi: 10.1016/j.oraloncology.2015.04.005.
    1. Liu Z, Gao J, Yang Y, Zhao H, Ma C, Yu T. Potential targets identified in adenoid cystic carcinoma point out new directions for further research. Am J Transl Res. 2021;13:1085–1108.
    1. van Weert S, van der Waal I, Witte BI, Leemans CR, Bloemena E. Histopathological grading of adenoid cystic carcinoma of the head and neck: analysis of currently used grading systems and proposal for a simplified grading scheme. Oral Oncol. 2015;51:71–76. doi: 10.1016/j.oraloncology.2014.10.007.
    1. Nightingale J, Lum B, Ladwa R, Simpson F, Panizza B. Adenoid cystic carcinoma: a review of clinical features, treatment targets and advances in improving the immune response to monoclonal antibody therapy. Biochim Biophys Acta Rev Cancer. 2021;1875:188523. doi: 10.1016/j.bbcan.2021.188523.
    1. Ali S, Palmer FL, Katabi N, Lee N, Shah JP, Patel SG, et al. Long-term local control rates of patients with adenoid cystic carcinoma of the head and neck managed by surgery and postoperative radiation. Laryngoscope. 2017;127:2265–2269. doi: 10.1002/lary.26565.
    1. Zhu Y, Zhu X, Xue X, Zhang Y, Hu C, Liu W, et al. Exploration of high-grade transformation and postoperative radiotherapy on prognostic analysis for primary adenoid cystic carcinoma of the head and neck. Front Oncol. 2021;11:647172. doi: 10.3389/fonc.2021.647172.
    1. van Weert S, Bloemena E, van der Waal I, de Bree R, Rietveld DH, Kuik JD, et al. Adenoid cystic carcinoma of the head and neck: a single-center analysis of 105 consecutive cases over a 30-year period. Oral Oncol. 2013;49:824–829. doi: 10.1016/j.oraloncology.2013.05.004.
    1. Bhayani MK, Yener M, El-Naggar A, Garden A, Hanna EY, Weber RS, et al. Prognosis and risk factors for early-stage adenoid cystic carcinoma of the major salivary glands. Cancer. 2012;118:2872–2878. doi: 10.1002/cncr.26549.
    1. Laurie SA, Ho AL, Fury MG, Sherman E, Pfister DG. Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review. Lancet Oncol. 2011;12:815–824. doi: 10.1016/S1470-2045(10)70245-X.
    1. van der Wal JE, Becking AG, Snow GB, van der Waal I. Distant metastases of adenoid cystic carcinoma of the salivary glands and the value of diagnostic examinations during follow-up. Head Neck. 2002;24:779–783. doi: 10.1002/hed.10126.
    1. Jung JH, Lee SW, Son SH, Kim CY, Lee CH, Jeong JH, et al. Clinical impact of (18) F-FDG positron emission tomography/CT on adenoid cystic carcinoma of the head and neck. Head Neck. 2017;39:447–455. doi: 10.1002/hed.24605.
    1. Choi M, Koo JS, Yoon JS. Recurred adenoid cystic carcinoma of lacrimal gland with aggressive local invasion to the maxillary bone marrow without increased uptake in PET-CT. Korean J Ophthalmol. 2015;29:68–70. doi: 10.3341/kjo.2015.29.1.68.
    1. Klein Nulent TJW, van Es RJJ, Krijger GC, de Bree R, Willems SM, de Keizer B. Prostate-specific membrane antigen PET imaging and immunohistochemistry in adenoid cystic carcinoma-a preliminary analysis. Eur J Nucl Med Mol Imaging. 2017;44:1614–1621. doi: 10.1007/s00259-017-3737-x.
    1. Nomura N, Pastorino S, Jiang P, Lambert G, Crawford JR, Gymnopoulos M, et al. Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases. Cancer Cell Int. 2014;14:26. doi: 10.1186/1475-2867-14-26.
    1. Moore M, Panjwani S, Mathew R, Crowley M, Liu YF, Aronova A, et al. Well-differentiated thyroid cancer neovasculature expresses prostate-specific membrane antigen-a possible novel therapeutic target. Endocr Pathol. 2017;28:339–344. doi: 10.1007/s12022-017-9500-9.
    1. Chang SS, O'Keefe DS, Bacich DJ, Reuter VE, Heston WD, Gaudin PB. Prostate-specific membrane antigen is produced in tumor-associated neovasculature. Clin Cancer Res. 1999;5:2674–2681.
    1. Al-Ahmadie HA, Olgac S, Gregor PD, Tickoo SK, Fine SW, Kondagunta GV, et al. Expression of prostate-specific membrane antigen in renal cortical tumors. Mod Pathol. 2008;21:727–732. doi: 10.1038/modpathol.2008.42.
    1. Jiao D, Li Y, Yang F, Han D, Wu J, Shi S, et al. Expression of prostate-specific membrane antigen in tumor-associated vasculature predicts poor prognosis in hepatocellular carcinoma. Clin Transl Gastroenterol. 2019;10:1–7. doi: 10.14309/ctg.0000000000000041.
    1. Wang HL, Wang SS, Song WH, Pan Y, Yu HP, Si TG, et al. Expression of prostate-specific membrane antigen in lung cancer cells and tumor neovasculature endothelial cells and its clinical significance. PLoS ONE. 2015;10:e0125924. doi: 10.1371/journal.pone.0125924.
    1. van Boxtel W, Lutje S, van Engen-van Grunsven ICH, Verhaegh GW, Schalken JA, Jonker MA, et al. (68)Ga-PSMA-HBED-CC PET/CT imaging for adenoid cystic carcinoma and salivary duct carcinoma: a phase 2 imaging study. Theranostics. 2020;10:2273–2283. doi: 10.7150/thno.38501.
    1. Klein Nulent TJW, Valstar MH, Smit LA, Smeele LE, Zuithoff NPA, de Keizer B, et al. Prostate-specific membrane antigen (PSMA) expression in adenoid cystic carcinoma of the head and neck. BMC Cancer. 2020;20:519. doi: 10.1186/s12885-020-06847-9.
    1. Bahk YW. On launching a new twenty-first century quarterly journal, nuclear medicine and molecular imaging. Nucl Med Mol Imaging. 2010;44:1–2. doi: 10.1007/s13139-009-0003-6.
    1. Lutje S, Sauerwein W, Lauenstein T, Bockisch A, Poeppel TD. In vivo visualization of prostate-specific membrane antigen in adenoid cystic carcinoma of the Salivary Gland. Clin Nucl Med. 2016;41:476–477. doi: 10.1097/RLU.0000000000001220.
    1. Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385:1091–1103. doi: 10.1056/NEJMoa2107322.
    1. Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, et al. [(177)Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021;397:797–804. doi: 10.1016/S0140-6736(21)00237-3.
    1. Sadaghiani MS, Sheikhbahaei S, Werner RA, Pienta KJ, Pomper MG, Solnes LB, et al. A systematic review and meta-analysis of the effectiveness and toxicities of lutetium-177-labeled prostate-specific membrane antigen-targeted radioligand therapy in metastatic castration-resistant prostate cancer. Eur Urol. 2021;80:82–94. doi: 10.1016/j.eururo.2021.03.004.
    1. Zang J, Fan X, Wang H, Liu Q, Wang J, Li H, et al. First-in-human study of (177)Lu-EB-PSMA-617 in patients with metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2019;46:148–158. doi: 10.1007/s00259-018-4096-y.
    1. Zang J, Liu Q, Sui H, Wang R, Jacobson O, Fan X, et al. (177)Lu-EB-PSMA radioligand therapy with escalating doses in patients with metastatic castration-resistant prostate cancer. J Nucl Med. 2020;61:1772–1778. doi: 10.2967/jnumed.120.242263.
    1. Fendler WP, Eiber M, Beheshti M, Bomanji J, Ceci F, Cho S, et al. (68)Ga-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. doi: 10.1007/s00259-017-3670-z.
    1. Werner-Wasik M, Nelson AD, Choi W, Arai Y, Faulhaber PF, Kang P, et al. What is the best way to contour lung tumors on PET scans? Multiobserver validation of a gradient-based method using a NSCLC digital PET phantom. Int J Radiat Oncol Biol Phys. 2012;82:1164–1171. doi: 10.1016/j.ijrobp.2010.12.055.
    1. 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(Suppl 1):122S–S150. doi: 10.2967/jnumed.108.057307.
    1. Moran CA, Suster S, Koss MN. Primary adenoid cystic carcinoma of the lung. A clinicopathologic and immunohistochemical study of 16 cases. Cancer. 1994;73:1390–7. doi: 10.1002/1097-0142(19940301)73:5<1390::AID-CNCR2820730513>;2-#.
    1. Ruhlmann V, Poeppel TD, Veit J, Nagarajah J, Umutlu L, Hoffmann TK, et al. Diagnostic accuracy of (18)F-FDG PET/CT and MR imaging in patients with adenoid cystic carcinoma. BMC Cancer. 2017;17:887. doi: 10.1186/s12885-017-3890-4.
    1. Uijen MJM, Derks YHW, Merkx RIJ, Schilham MGM, Roosen J, Prive BM, et al. PSMA radioligand therapy for solid tumors other than prostate cancer: background, opportunities, challenges, and first clinical reports. Eur J Nucl Med Mol Imaging. 2021;48:4350–4368. doi: 10.1007/s00259-021-05433-w.
    1. Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [(177)Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19:825–833. doi: 10.1016/S1470-2045(18)30198-0.
    1. Has Simsek D, Kuyumcu S, Agaoglu FY, Unal SN. Radionuclide therapy with 177Lu-PSMA in a case of metastatic adenoid cystic carcinoma of the parotid. Clin Nucl Med. 2019;44:764–766. doi: 10.1097/RLU.0000000000002645.
    1. Grunig H, Maurer A, Thali Y, Kovacs Z, Strobel K, Burger IA, et al. Focal unspecific bone uptake on [(18)F]-PSMA-1007 PET: a multicenter retrospective evaluation of the distribution, frequency, and quantitative parameters of a potential pitfall in prostate cancer imaging. Eur J Nucl Med Mol Imaging. 2021;48:4483–4494. doi: 10.1007/s00259-021-05424-x.

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