Skip to main content
Erschienen in: Annals of Nuclear Medicine 5/2020

06.03.2020 | Original Article

Diagnosis of bladder cancer using 18F-labeled α-methyl-phenylalanine tracers in a mouse model

verfasst von: Isa Mahendra, Hirofumi Hanaoka, Aiko Yamaguchi, Tumenjargal Amartuvshin, Yoshito Tsushima

Erschienen in: Annals of Nuclear Medicine | Ausgabe 5/2020

Einloggen, um Zugang zu erhalten

Abstract

Objective

Although 2-18F-fluoro-2-deoxy-glucose (18F-FDG) has established roles in the diagnosis of a variety of cancers, it has limited value in the detection of primary/recurrent lesions in the bladder, mainly because of interference by the pooled radioactivity in the urine. Our previous study revealed promising properties of l- and d-2-18F-α-methyl-phenylalanine (2-18F-FAMP) as radiotracers; i.e., their rapid blood clearance and low renal accumulation. In the present study we evaluated the utility of l- and d-2-18F-FAMP for imaging bladder cancer in a mouse model.

Methods

We used the human bladder cancer cell line HT1376 to prepare a bladder cancer xenograft model in mice bearing both orthotopic and subcutaneous tumors. Biodistribution and PET imaging studies were performed at 1 and 3 h after injection of l-2-18F-FAMP or d-2-18F-FAMP. 18F-FDG was used as a control.

Results

At 1 h after injection, greater accumulations of both l-2-18F-FAMP and d-2-18F-FAMP were observed in the orthotopic tumors compared to 18F-FDG. The orthotopic tumor-to-muscle ratio of d-2-18F-FAMP was significantly higher than that of 18F-FDG (p < 0.01), because of the rapid blood clearance of d-2-18F-FAMP. l-2-18F-FAMP showed the highest subcutaneous tumor-to-muscle ratio (p < 0.01) due to its high subcutaneous tumor uptake. Compared to l-2-18F-FAMP, d-2-18F-FAMP exhibited faster clearance and lower kidney accumulation. In the PET imaging studies, l- and d-2-18F-FAMP both clearly visualized the orthotopic bladder tumors at 1 h after injection.

Conclusion

Our study showed that l-2-18F-FAMP and d-2-18F-FAMP have the potential to detect bladder cancer.
Literatur
1.
Zurück zum Zitat 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.CrossRef 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.CrossRef
2.
Zurück zum Zitat Kamat AM, Hahn NM, Efstathiou JA, Lerner SP, Malmström P-U, Choi W, et al. Bladder cancer. Lancet. 2016;388:2796–810.CrossRef Kamat AM, Hahn NM, Efstathiou JA, Lerner SP, Malmström P-U, Choi W, et al. Bladder cancer. Lancet. 2016;388:2796–810.CrossRef
3.
Zurück zum Zitat Totaro A, Pinto F, Brescia A, Racioppi M, Cappa E, D’Agostino D, et al. Imaging in bladder cancer: present role and future perspectives. Urol Int. 2010;85:373–80.CrossRef Totaro A, Pinto F, Brescia A, Racioppi M, Cappa E, D’Agostino D, et al. Imaging in bladder cancer: present role and future perspectives. Urol Int. 2010;85:373–80.CrossRef
4.
Zurück zum Zitat Choe J, Braschi-Amirfarzan M, Tirumani SH, Shinagare AB, Kim KW, Ramaiya NH, et al. Updates for the radiologist in non-muscle-invasive, muscle-invasive, and metastatic bladder cancer. Abdom Radiol. 2017;42:2710–24.CrossRef Choe J, Braschi-Amirfarzan M, Tirumani SH, Shinagare AB, Kim KW, Ramaiya NH, et al. Updates for the radiologist in non-muscle-invasive, muscle-invasive, and metastatic bladder cancer. Abdom Radiol. 2017;42:2710–24.CrossRef
5.
Zurück zum Zitat Alfred Witjes J, Lebret T, Compérat EM, Cowan NC, De Santis M, Bruins HM, et al. Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol. 2017;71:462–75.CrossRef Alfred Witjes J, Lebret T, Compérat EM, Cowan NC, De Santis M, Bruins HM, et al. Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol. 2017;71:462–75.CrossRef
6.
Zurück zum Zitat Avril N. GLUT1 expression in tissue and 18F-FDG uptake. J Nucl Med. 2004;45:930–3.PubMed Avril N. GLUT1 expression in tissue and 18F-FDG uptake. J Nucl Med. 2004;45:930–3.PubMed
7.
Zurück zum Zitat Razik A, Das C, Sharma S. PET-CT and PET-MR in urological cancers other than prostate cancer: an update on state of the art. Indian J Urol. 2018;34:20.CrossRef Razik A, Das C, Sharma S. PET-CT and PET-MR in urological cancers other than prostate cancer: an update on state of the art. Indian J Urol. 2018;34:20.CrossRef
8.
Zurück zum Zitat Schöder H, Larson SM. Positron emission tomography for prostate, bladder, and renal cancer. Semin Nucl Med. 2004;34:274–92.CrossRef Schöder H, Larson SM. Positron emission tomography for prostate, bladder, and renal cancer. Semin Nucl Med. 2004;34:274–92.CrossRef
9.
Zurück zum Zitat Achmad A, Bhattarai A, Yudistiro R, Heryanto YD, Higuchi T, Tsushima Y. The diagnostic performance of 18F-FAMT PET and 18F-FDG PET for malignancy detection: a meta-analysis. BMC Med Imaging. 2017;17:66.CrossRef Achmad A, Bhattarai A, Yudistiro R, Heryanto YD, Higuchi T, Tsushima Y. The diagnostic performance of 18F-FAMT PET and 18F-FDG PET for malignancy detection: a meta-analysis. BMC Med Imaging. 2017;17:66.CrossRef
10.
Zurück zum Zitat Watabe T, Ikeda H, Nagamori S, Wiriyasermkul P, Tanaka Y, Naka S, et al. 18F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with 18F-FDG and 11C-Methionine PET. Eur J Nucl Med Mol Imaging. 2017;44:321–31.CrossRef Watabe T, Ikeda H, Nagamori S, Wiriyasermkul P, Tanaka Y, Naka S, et al. 18F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with 18F-FDG and 11C-Methionine PET. Eur J Nucl Med Mol Imaging. 2017;44:321–31.CrossRef
11.
Zurück zum Zitat Maimaiti M, Sakamoto S, Sugiura M, Xu M, Yamada Y, Higuchi K, et al. An L-type amino acid transporte 1 inhibitor: JPH203 suppresses bladder cancer growth and invansion via IGFBP-5. J Urol. 2019;201:e724. Maimaiti M, Sakamoto S, Sugiura M, Xu M, Yamada Y, Higuchi K, et al. An L-type amino acid transporte 1 inhibitor: JPH203 suppresses bladder cancer growth and invansion via IGFBP-5. J Urol. 2019;201:e724.
12.
Zurück zum Zitat Hanaoka H, Ohshima Y, Yamaguchi A, Suzuki H, Ishioka NS, Higuchi T, et al. Novel 18F-labeled α-methyl-phenylalanine derivative with high tumor accumulation and ideal pharmacokinetics for tumor-specific imaging. Mol Pharm. 2019;16:3609–16.CrossRef Hanaoka H, Ohshima Y, Yamaguchi A, Suzuki H, Ishioka NS, Higuchi T, et al. Novel 18F-labeled α-methyl-phenylalanine derivative with high tumor accumulation and ideal pharmacokinetics for tumor-specific imaging. Mol Pharm. 2019;16:3609–16.CrossRef
13.
Zurück zum Zitat Ferreira-Teixeira M, Parada B, Rodrigues-Santos P, Alves V, Ramalho JS, Caramelo F, et al. Functional and molecular characterization of cancer stem-like cells in bladder cancer: a potential signature for muscle-invasive tumors. Oncotarget. 2015;6:36185–201.CrossRef Ferreira-Teixeira M, Parada B, Rodrigues-Santos P, Alves V, Ramalho JS, Caramelo F, et al. Functional and molecular characterization of cancer stem-like cells in bladder cancer: a potential signature for muscle-invasive tumors. Oncotarget. 2015;6:36185–201.CrossRef
14.
Zurück zum Zitat Fu C-L, Apelo CA, Torres B, Thai KH, Hsieh MH. Mouse bladder wall injection. J Vis Exp. 2011;53:1–3. Fu C-L, Apelo CA, Torres B, Thai KH, Hsieh MH. Mouse bladder wall injection. J Vis Exp. 2011;53:1–3.
15.
Zurück zum Zitat Jäger W, Moskalev I, Janssen C, Hayashi T, Awrey S, Gust KM, et al. Ultrasound-guided intramural inoculation of orthotopic bladder cancer xenografts: a novel high-precision approach. PLoS ONE. 2013;8:e59536.CrossRef Jäger W, Moskalev I, Janssen C, Hayashi T, Awrey S, Gust KM, et al. Ultrasound-guided intramural inoculation of orthotopic bladder cancer xenografts: a novel high-precision approach. PLoS ONE. 2013;8:e59536.CrossRef
16.
Zurück zum Zitat Abbas A, Beamish C, McGirr R, Demarco J, Cockburn N, Krokowski D, et al. Characterization of 5-(2–18F-fluoroethoxy)-l-tryptophan for PET imaging of the pancreas. F1000Research. 2016;5:1851.CrossRef Abbas A, Beamish C, McGirr R, Demarco J, Cockburn N, Krokowski D, et al. Characterization of 5-(2–18F-fluoroethoxy)-l-tryptophan for PET imaging of the pancreas. F1000Research. 2016;5:1851.CrossRef
17.
Zurück zum Zitat Nijjar S, Patterson J, Ducharme J, Leslie WD, Demeter SJ. The effect of furosemide dose timing on bladder activity in oncology imaging with 18F-fluorodeoxyglucose PET/CT. Nucl Med Commun. 2010;31:167–72.CrossRef Nijjar S, Patterson J, Ducharme J, Leslie WD, Demeter SJ. The effect of furosemide dose timing on bladder activity in oncology imaging with 18F-fluorodeoxyglucose PET/CT. Nucl Med Commun. 2010;31:167–72.CrossRef
18.
Zurück zum Zitat Anjos DA, Etchebehere ECSC, Ramos CD, Santos AO, Albertotti C, Camargo EE. 18F-FDG PET/CT delayed images after diuretic for restaging invasive bladder cancer. J Nucl Med. 2007;48:764–70.CrossRef Anjos DA, Etchebehere ECSC, Ramos CD, Santos AO, Albertotti C, Camargo EE. 18F-FDG PET/CT delayed images after diuretic for restaging invasive bladder cancer. J Nucl Med. 2007;48:764–70.CrossRef
19.
Zurück zum Zitat Hanaoka H, Ohshima Y, Suzuki Y, Yamaguchi A, Watanabe S, Uehara T, et al. Development of a widely usable amino acid tracer: 76Br-α-methyl-phenylalanine for tumor PET imaging. J Nucl Med. 2015;56:791–7.CrossRef Hanaoka H, Ohshima Y, Suzuki Y, Yamaguchi A, Watanabe S, Uehara T, et al. Development of a widely usable amino acid tracer: 76Br-α-methyl-phenylalanine for tumor PET imaging. J Nucl Med. 2015;56:791–7.CrossRef
20.
Zurück zum Zitat GuhaSarkar S, Banerjee R. Intravesical drug delivery: challenges, current status, opportunities and novel strategies. J Control Release. 2010;148:147–59.CrossRef GuhaSarkar S, Banerjee R. Intravesical drug delivery: challenges, current status, opportunities and novel strategies. J Control Release. 2010;148:147–59.CrossRef
21.
Zurück zum Zitat Ohshima Y, Hanaoka H, Tominaga H, Kanai Y, Kaira K, Yamaguchi A, et al. Biological evaluation of 3-[18F]fluoro-α-methyl-d-tyrosine (D-[18F]FAMT) as a novel amino acid tracer for positron emission tomography. Ann Nucl Med. 2013;27:314–24.CrossRef Ohshima Y, Hanaoka H, Tominaga H, Kanai Y, Kaira K, Yamaguchi A, et al. Biological evaluation of 3-[18F]fluoro-α-methyl-d-tyrosine (D-[18F]FAMT) as a novel amino acid tracer for positron emission tomography. Ann Nucl Med. 2013;27:314–24.CrossRef
Metadaten
Titel
Diagnosis of bladder cancer using 18F-labeled α-methyl-phenylalanine tracers in a mouse model
verfasst von
Isa Mahendra
Hirofumi Hanaoka
Aiko Yamaguchi
Tumenjargal Amartuvshin
Yoshito Tsushima
Publikationsdatum
06.03.2020
Verlag
Springer Singapore
Erschienen in
Annals of Nuclear Medicine / Ausgabe 5/2020
Print ISSN: 0914-7187
Elektronische ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-020-01452-z

Weitere Artikel der Ausgabe 5/2020

Annals of Nuclear Medicine 5/2020 Zur Ausgabe