PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions
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Prostate-specific membrane antigen (PSMA) is a cell surface protein with high expression in prostate carcinoma (PC) cells. Recently, procedures have been developed to label PSMA ligands with 68Ga, 99mTc and 123/124/131I. Our initial experience with Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)](68Ga-PSMA) suggests that this novel tracer can detect PC relapses and metastases with high contrast. The aim of this study was to investigate its biodistribution in normal tissues and tumour lesions.
A total of 37 patients with PC and rising prostate-specific antigen (PSA) levels were subjected to 68Ga-PSMA positron emission tomography (PET)/CT. Quantitative assessment of tracer uptake was performed 1 and 3 h post-injection (p.i.) by analysis of mean and maximum standardized uptake values (SUVmean/max) of several organs and 65 tumour lesions. Subsequently, tumour to background ratios were calculated.
The PET/CT images showed intense tracer uptake in both kidneys and salivary glands. Moderate uptake was seen in lacrimal glands, liver, spleen and in small and large bowel. Quantitative assessment revealed excellent contrast between tumour lesions and most normal tissues. Of 37 patients, 31 (83.8 %) showed at least one lesion suspicious for cancer at a detection rate of 60 % at PSA <2.2 ng/ml and 100 % at PSA >2.2 ng/ml. Median tumour to background ratios were 18.8 (2.4–158.3) in early images and 28.3 (2.9–224.0) in late images.
The biodistribution of the novel 68Ga-PSMA tracer and its ability to detect PC lesions was analysed in 37 patients. Within healthy organs, kidneys and salivary glands demonstrated the highest radiotracer uptake. Lesions suspicious for PC presented with excellent contrast as early as 1 h p.i. with high detection rates even at low PSA levels.
- Sweat, SD, Pacelli, A, Murphy, GP, Bostwick, DG (1998) Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology 52: pp. 637-640 CrossRef
- Mannweiler, S, Amersdorfer, P, Trajanoski, S, Terrett, JA, King, D, Mehes, G (2009) Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis. Pathol Oncol Res 15: pp. 167-172 CrossRef
- Ghosh, A, Heston, WD (2004) Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem 91: pp. 528-539 CrossRef
- Bander, NH (2006) Technology insight: monoclonal antibody imaging of prostate cancer. Nat Clin Pract Urol 3: pp. 216-225 CrossRef
- Liu, H, Moy, P, Kim, S, Xia, Y, Rajasekaran, A, Navarro, V (1997) Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium. Cancer Res 57: pp. 3629-3634
- Hillier, SM, Maresca, KP, Femia, FJ, Marquis, JC, Foss, CA, Nguyen, N (2009) Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer. Cancer Res 69: pp. 6932-6940 CrossRef
- Eder, M, Schäfer, M, Bauder-Wüst, U, Hull, WE, Wangler, C, Mier, W (2012) (68)Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem 23: pp. 688-697 CrossRef
- Banerjee, SR, Foss, CA, Castanares, M, Mease, RC, Byun, Y, Fox, JJ (2008) Synthesis and evaluation of technetium-99m- and rhenium-labeled inhibitors of the prostate-specific membrane antigen (PSMA). J Med Chem 51: pp. 4504-4517 CrossRef
- Afshar-Oromieh, A, Haberkorn, U, Eder, M, Eisenhut, M, Zechmann, C (2012) [(68)Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: comparison with (18)F-FECH. Eur J Nucl Med Mol Imaging 39: pp. 1085-1086 CrossRef
- Schuhmacher, J, Maier-Borst, W (1981) A new 68Ge/68Ga radioisotope generator system for production of 68Ga in dilute HCl. Int J Appl Radiat Isot 32: pp. 31-36 CrossRef
- Schäfer, M, Bauder-Wüst, U, Leotta, K, Zoller, F, Mier, W, Haberkorn, U (2012) A dimerized urea-based inhibitor of the prostate-specific membrane antigen for 68Ga-PET imaging of prostate cancer. EJNMMI Res 2: pp. 23 CrossRef
- Human protein atlas. FOLH1. http://www.proteinatlas.org/ENSG00000086205/normal.
- Silver, DA, Pellicer, I, Fair, WR, Heston, WD, Cordon-Cardo, C (1997) Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 3: pp. 81-85
- Gordon, IO, Tretiakova, MS, Noffsinger, AE, Hart, J, Reuter, VE, Al-Ahmadie, HA (2008) Prostate-specific membrane antigen expression in regeneration and repair. Mod Pathol 21: pp. 1421-1427 CrossRef
- Maraj, BH, Aldersley, MA, Markham, AF (1998) Prostate-specific membrane antigen expression in the duodenum: implications in coeliac disease and immunotherapy for prostate cancer. Lancet 351: pp. 1559-1560 CrossRef
- Bostwick, DG, Pacelli, A, Blute, M, Roche, P, Murphy, GP (1998) Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer 82: pp. 2256-2261 CrossRef
- PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions
European Journal of Nuclear Medicine and Molecular Imaging
Volume 40, Issue 4 , pp 486-495
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Prostate cancer
- Positron emission tomography
- Prostate-specific membrane antigen
- Industry Sectors
- Author Affiliations
- 1. Department of Nuclear Medicine, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
- 2. Department of Radiopharmaceutical Chemistry, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, Germany
- 3. National Center for Tumor Diseases (NCT)/DKFZ, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany
- 4. Department of Urology, University Hospital of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, Germany
- 5. Department of Biostatistics, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, Germany
- 6. Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Centre, Heidelberg, Germany