INTRODUCTION: Tryptophan oxidation via the kynurenine pathway is an important mechanism of tumoral immunoresistance. Increased tryptophan metabolism via the serotonin pathway has been linked to malignant progression in breast cancer. In this study, we combined quantitative positron emission tomography (PET) with tumor immunohistochemistry to analyze tryptophan transport and metabolism in breast cancer. METHODS: Dynamic α-[(11)C]methyl-l-tryptophan (AMT) PET was performed in nine women with stage II-IV breast cancer. PET tracer kinetic modeling was performed in all tumors. Expression of L-type amino acid transporter 1 (LAT1), indoleamine 2,3-dioxygenase (IDO; the initial and rate-limiting enzyme of the kynurenine pathway) and tryptophan hydroxylase 1 (TPH1; the initial enzyme of the serotonin pathway) was assessed by immunostaining of resected tumor specimens. RESULTS: Tumor AMT uptake peaked at 5-20 min postinjection in seven tumors; the other two cases showed protracted tracer accumulation. Tumor standardized uptake values (SUVs) varied widely (2.6-9.8) and showed a strong positive correlation with volume of distribution values derived from kinetic analysis (P<.01). Invasive ductal carcinomas (n=6) showed particularly high AMT SUVs (range, 4.7-9.8). Moderate to strong immunostaining for LAT1, IDO and TPH1 was detected in most tumor cells. CONCLUSIONS: Breast cancers show differential tryptophan kinetics on dynamic PET. SUVs measured 5-20 min postinjection reflect reasonably the tracer's volume of distribution. Further studies are warranted to determine if in vivo AMT accumulation in these tumors is related to tryptophan metabolism via the kynurenine and serotonin pathways.
INTRODUCTION:Tryptophan oxidation via the kynurenine pathway is an important mechanism of tumoral immunoresistance. Increased tryptophan metabolism via the serotonin pathway has been linked to malignant progression in breast cancer. In this study, we combined quantitative positron emission tomography (PET) with tumor immunohistochemistry to analyze tryptophan transport and metabolism in breast cancer. METHODS: Dynamic α-[(11)C]methyl-l-tryptophan (AMT) PET was performed in nine women with stage II-IV breast cancer. PET tracer kinetic modeling was performed in all tumors. Expression of L-type amino acid transporter 1 (LAT1), indoleamine 2,3-dioxygenase (IDO; the initial and rate-limiting enzyme of the kynurenine pathway) and tryptophan hydroxylase 1 (TPH1; the initial enzyme of the serotonin pathway) was assessed by immunostaining of resected tumor specimens. RESULTS:TumorAMT uptake peaked at 5-20 min postinjection in seven tumors; the other two cases showed protracted tracer accumulation. Tumor standardized uptake values (SUVs) varied widely (2.6-9.8) and showed a strong positive correlation with volume of distribution values derived from kinetic analysis (P<.01). Invasive ductal carcinomas (n=6) showed particularly high AMT SUVs (range, 4.7-9.8). Moderate to strong immunostaining for LAT1, IDO and TPH1 was detected in most tumor cells. CONCLUSIONS:Breast cancers show differential tryptophan kinetics on dynamic PET. SUVs measured 5-20 min postinjection reflect reasonably the tracer's volume of distribution. Further studies are warranted to determine if in vivo AMT accumulation in these tumors is related to tryptophan metabolism via the kynurenine and serotonin pathways.
Authors: Jonathan D Silk; Samira Lakhal; Robert Laynes; Laura Vallius; Ioannis Karydis; Cornelius Marcea; C A Richard Boyd; Vincenzo Cerundolo Journal: J Immunol Date: 2011-07-08 Impact factor: 5.422
Authors: Csaba Juhász; Diane C Chugani; Otto Muzik; Dafang Wu; Andrew E Sloan; Geoffrey Barger; Craig Watson; Aashit K Shah; Sandeep Sood; Eser L Ergun; Tom J Mangner; Pulak K Chakraborty; William J Kupsky; Harry T Chugani Journal: J Cereb Blood Flow Metab Date: 2006-03 Impact factor: 6.200
Authors: Catherine Uyttenhove; Luc Pilotte; Ivan Théate; Vincent Stroobant; Didier Colau; Nicolas Parmentier; Thierry Boon; Benoît J Van den Eynde Journal: Nat Med Date: 2003-09-21 Impact factor: 53.440
Authors: Csaba Juhász; Otto Muzik; Xin Lu; M Salik Jahania; Ayman O Soubani; Majid Khalaf; Fangyu Peng; Thomas J Mangner; Pulak K Chakraborty; Diane C Chugani Journal: J Nucl Med Date: 2009-02-17 Impact factor: 10.057
Authors: Lee Jia; Karen Schweikart; Joseph Tomaszewski; John G Page; Patricia E Noker; Sarah A Buhrow; Joel M Reid; Matthew M Ames; David H Munn Journal: Food Chem Toxicol Date: 2007-08-10 Impact factor: 6.023
Authors: S Esseghir; J S Reis-Filho; A Kennedy; M James; M J O'Hare; R Jeffery; R Poulsom; C M Isacke Journal: J Pathol Date: 2006-12 Impact factor: 7.996
Authors: Jean Henrottin; Astrid Zervosen; Christian Lemaire; Frédéric Sapunaric; Sophie Laurent; Benoit Van den Eynde; Serge Goldman; Alain Plenevaux; André Luxen Journal: ACS Med Chem Lett Date: 2015-01-25 Impact factor: 4.345
Authors: Anthony R Guastella; Sharon K Michelhaugh; Neil V Klinger; Hassan A Fadel; Sam Kiousis; Rouba Ali-Fehmi; William J Kupsky; Csaba Juhász; Sandeep Mittal Journal: J Neurooncol Date: 2018-04-17 Impact factor: 4.130
Authors: Sharon K Michelhaugh; Otto Muzik; Anthony R Guastella; Neil V Klinger; Lisa A Polin; Hancheng Cai; Yangchun Xin; Thomas J Mangner; Shaohui Zhang; Csaba Juhász; Sandeep Mittal Journal: J Nucl Med Date: 2016-10-20 Impact factor: 10.057
Authors: Edit Bosnyák; David O Kamson; Anthony R Guastella; Kaushik Varadarajan; Natasha L Robinette; William J Kupsky; Otto Muzik; Sharon K Michelhaugh; Sandeep Mittal; Csaba Juhász Journal: Neuro Oncol Date: 2015-06-18 Impact factor: 12.300