Evaluation of Arginine Deiminase Treatment in Melanoma Xenografts Using (18)F-FLT PET

Overview

Journal Mol Imaging Biol

Publisher Springer

Specialties Molecular Biology
Radiology

Date 2013 Jun 1

PMID 23722880

Citations 11

Authors

Lars Stelter

Simon Fuchs

Achim A Jungbluth

Gerd Ritter

Valerie A Longo

Pat Zanzonico

Nathanael Raschzok

Igor M Sauer

John S Bomalaski

Steven M Larson

Affiliations

Soon will be listed here.

Abstract

Purpose: This study aims to develop a molecular imaging strategy for response assessment of arginine deiminase (ADI) treatment in melanoma xenografts using 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]-FLT) positron emission tomography (PET).

Procedures: F-FLT response to ADI therapy was studied in preclinical models of melanoma in vitro and in vivo. The molecular mechanism of response to ADI therapy was investigated, with a particular emphasis on biological pathways known to regulate (18)F-FLT metabolism.

Results: Proliferation of SK-MEL-28 melanoma tumors was potently inhibited by ADI treatment. However, no metabolic response was observed in FLT PET, presumably based on the known ADI-induced degradation of PTEN, followed by instability of the tumor suppressor p53 and a relative overexpression of thymidine kinase 1, the enzyme mainly responsible for intracellular FLT processing.

Conclusion: The specific pharmacological properties of ADI preclude using (18)F-FLT to evaluate clinical response in melanoma and argue for further studies to explore the use of other clinically applicable PET tracers in ADI treatment.

Citing Articles

Cyproheptadine inhibits in vitro and in vivo lung metastasis and drives metabolic rewiring.

Shannar A, Sarwar M, Dave P, Chou P, Peter R, Xu J Mol Biol Rep. 2024; 51(1):1139.

PMID: 39522095 PMC: 11551078. DOI: 10.1007/s11033-024-10033-6.

Metabolic control of cancer metastasis: role of amino acids at secondary organ sites.

Karno B, Edwards D, Chen J Oncogene. 2023; 42(47):3447-3456.

PMID: 37848626 PMC: 11323979. DOI: 10.1038/s41388-023-02868-3.

Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.

Chu Y, Lai M, Yeh C Int J Mol Sci. 2023; 24(13).

PMID: 37445845 PMC: 10341449. DOI: 10.3390/ijms241310668.

Role of 3'-Deoxy-3'-[F] Fluorothymidine Positron Emission Tomography-Computed Tomography as a Predictive Biomarker in Argininosuccinate Synthetase 1-Deficient Thoracic Cancers Treated With Pegargiminase.

Szyszko T, Dunn J, Phillips M, Bomalaski J, Sheaff M, Ellis S JTO Clin Res Rep. 2022; 3(9):100382.

PMID: 36082278 PMC: 9445378. DOI: 10.1016/j.jtocrr.2022.100382.

A Phase 1 study of ADI-PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1-negative metastatic uveal melanoma.

Chan P, Phillips M, Ellis S, Johnston A, Feng X, Arora A Pigment Cell Melanoma Res. 2022; 35(4):461-470.

PMID: 35466524 PMC: 9322321. DOI: 10.1111/pcmr.13042.

References

Lucignani G, Larson S . Doctor, what does my future hold? The prognostic value of FDG-PET in solid tumours. Eur J Nucl Med Mol Imaging. 2010; 37(5):1032-8. DOI: 10.1007/s00259-010-1428-y. View

Fatema C, Zhao S, Zhao Y, Murakami M, Yu W, Nishijima K . Monitoring tumor proliferative response to radiotherapy using (18)F-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67. Ann Nucl Med. 2013; 27(4):355-62. DOI: 10.1007/s12149-013-0693-9. View

Feun L, Savaraj N . Pegylated arginine deiminase: a novel anticancer enzyme agent. Expert Opin Investig Drugs. 2006; 15(7):815-22. PMC: 3086545. DOI: 10.1517/13543784.15.7.815. View

Cui X, Witalison E, Chumanevich A, Chumanevich A, Poudyal D, Subramanian V . The induction of microRNA-16 in colon cancer cells by protein arginine deiminase inhibition causes a p53-dependent cell cycle arrest. PLoS One. 2013; 8(1):e53791. PMC: 3538596. DOI: 10.1371/journal.pone.0053791. View

Syed N, Langer J, Janczar K, Singh P, Lo Nigro C, Lattanzio L . Epigenetic status of argininosuccinate synthetase and argininosuccinate lyase modulates autophagy and cell death in glioblastoma. Cell Death Dis. 2013; 4:e458. PMC: 3563985. DOI: 10.1038/cddis.2012.197. View

Larson S, Schwartz L . 18F-FDG PET as a candidate for "qualified biomarker": functional assessment of treatment response in oncology. J Nucl Med. 2006; 47(6):901-3. View

Rasey J, Grierson J, Wiens L, Kolb P, Schwartz J . Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells. J Nucl Med. 2002; 43(9):1210-7. View

Kobayashi E, Masuda M, Nakayama R, Ichikawa H, Satow R, Shitashige M . Reduced argininosuccinate synthetase is a predictive biomarker for the development of pulmonary metastasis in patients with osteosarcoma. Mol Cancer Ther. 2010; 9(3):535-44. DOI: 10.1158/1535-7163.MCT-09-0774. View

Plotnik D, McLaughlin L, Chan J, Redmayne-Titley J, Schwartz J . The role of nucleoside/nucleotide transport and metabolism in the uptake and retention of 3'-fluoro-3'-deoxythymidine in human B-lymphoblast cells. Nucl Med Biol. 2011; 38(7):979-86. PMC: 3190124. DOI: 10.1016/j.nucmedbio.2011.03.009. View

10.

Izzo F, Marra P, Beneduce G, Castello G, Vallone P, De Rosa V . Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from phase I/II studies. J Clin Oncol. 2004; 22(10):1815-22. DOI: 10.1200/JCO.2004.11.120. View

11.

Hoglund J, Shirvan A, Antoni G, Gustavsson S, Langstrom B, Ringheim A . 18F-ML-10, a PET tracer for apoptosis: first human study. J Nucl Med. 2011; 52(5):720-5. DOI: 10.2967/jnumed.110.081786. View

12.

Hoshikawa H, Nishiyama Y, Kishino T, Yamamoto Y, Haba R, Mori N . Comparison of FLT-PET and FDG-PET for visualization of head and neck squamous cell cancers. Mol Imaging Biol. 2010; 13(1):172-7. DOI: 10.1007/s11307-010-0331-z. View

13.

Dillon B, Prieto V, Curley S, Ensor C, Holtsberg F, Bomalaski J . Incidence and distribution of argininosuccinate synthetase deficiency in human cancers: a method for identifying cancers sensitive to arginine deprivation. Cancer. 2004; 100(4):826-33. DOI: 10.1002/cncr.20057. View

14.

Plotnik D, McLaughlin L, Krohn K, Schwartz J . The effects of 5-fluoruracil treatment on 3'-fluoro-3'-deoxythymidine (FLT) transport and metabolism in proliferating and non-proliferating cultures of human tumor cells. Nucl Med Biol. 2012; 39(7):970-6. PMC: 3435469. DOI: 10.1016/j.nucmedbio.2012.03.009. View

15.

Mayo L, Dixon J, Durden D, Tonks N, Donner D . PTEN protects p53 from Mdm2 and sensitizes cancer cells to chemotherapy. J Biol Chem. 2001; 277(7):5484-9. DOI: 10.1074/jbc.M108302200. View

16.

Kelly M, Jungbluth A, Wu B, Bomalaski J, Old L, Ritter G . Arginine deiminase PEG20 inhibits growth of small cell lung cancers lacking expression of argininosuccinate synthetase. Br J Cancer. 2011; 106(2):324-32. PMC: 3261683. DOI: 10.1038/bjc.2011.524. View

17.

Stelter L, Evans M, Jungbluth A, Zanzonico P, Ritter G, Ku T . Novel mechanistic insights into arginine deiminase pharmacology suggest 18F-FDG is not suitable to evaluate clinical response in melanoma. J Nucl Med. 2012; 53(2):281-6. DOI: 10.2967/jnumed.111.092973. View

18.

Liu W, Zhou Y, Reske S, Shen C . PTEN mutation: many birds with one stone in tumorigenesis. Anticancer Res. 2009; 28(6A):3613-9. View

19.

Szlosarek P, Luong P, Phillips M, Baccarini M, Stephen E, Szyszko T . Metabolic response to pegylated arginine deiminase in mesothelioma with promoter methylation of argininosuccinate synthetase. J Clin Oncol. 2013; 31(7):e111-3. DOI: 10.1200/JCO.2012.42.1784. View

20.

You M, Savaraj N, Wangpaichitr M, Wu C, Kuo M, Varona-Santos J . The combination of ADI-PEG20 and TRAIL effectively increases cell death in melanoma cell lines. Biochem Biophys Res Commun. 2010; 394(3):760-6. PMC: 2860865. DOI: 10.1016/j.bbrc.2010.03.066. View