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Pilot Study of the Utility of the Synthetic PET Amino-Acid Radiotracer Anti-1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid for the Noninvasive Imaging of Pulmonary Lesions

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Abstract

Purpose

Anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-[18F]FACBC) is a synthetic amino acid positron emission tomography (PET) radiotracer with utility in detection of prostate carcinoma and brain tumors and has also been shown to have uptake in lung tumor cell lines. The purpose of this study is to determine the uptake characteristics of anti-3-[18F]FACBC in lung carcinoma and if this radiotracer may help characterize pulmonary lesions.

Procedures

Ten patients with pulmonary lesions scheduled for surgical resection or biopsy underwent 45-min dynamic PET-CT imaging of the thorax after IV injection of 214.6–384.8MBq of anti-3-[18F]FACBC. Anti-3-[18F]FACBC uptake was compared with that of routine 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) PET-CT scans of the same patient and validated with a combination of pathology, imaging and clinical follow-up. Immunohistochemistry for Ki-67 was performed on tissue samples.

Results

There were nine malignant (seven lung nodules and two mediastinal nodes), two inflammatory, and one carcinoid lesion ranging from 1 to 3.75 cm. Mean(±SD) SUVmax of malignant lesions was 6.2(±2.6), 5.9(±2.7), 5.9(±3.4), and 5.7(±3.3), at 8, 16, 28, and 40 min, respectively; while for inflammatory lesions at the same time points, 4.1(±0.6), 3.3(±0.9), 2.2(±0.03), and 2.3(±0.03), respectively. The carcinoid tumor had SUVmax of 2.8, 2.6, 1.5, and 0.9 at similar time points. Mean SUVmax of all malignant lesions was higher than that of inflammatory lesions for anti-3-[18F]FACBC, and was statistically significant at greater than 28 min post-radiotracer infusion (p < 0.05). There was no significant correlation of anti-3-[18F]FACBC activity with Ki67, though there was a positive trend. There was a strong correlation between anti-3-[18F]FACBC and [18F]FDG uptake.

Conclusions

Anti-3-[18F]FACBC uptake in malignant lesions is greater than in inflammatory lesions with a higher degree of separation of uptake on delayed imaging. More comprehensive study is required to determine the diagnostic performance of anti-3-[18F]FACBC in the characterization of pulmonary lesions.

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References

  1. Kim SK, Allen-Auerbach M, Goldin J, Fueger BJ et al (2007) Accuracy of PET/CT in characterization of solitary pulmonary lesions. J Nucl Med 48:214–220

    PubMed  Google Scholar 

  2. American Cancer Society (2012) Cancer Facts & Figures 2012. American Cancer Society, Atlanta

    Google Scholar 

  3. Ost DFA (2004) Management strategies for the solitary pulmonary nodule. Curr Opin Pulm Med 10:272–278

    Article  PubMed  Google Scholar 

  4. Winer-Muram HT (2006) The solitary pulmonary nodule. Radiology 239:34–49

    Article  PubMed  Google Scholar 

  5. Croft DR, Trapp J, Kernstine K et al (2002) FDG-PET imaging and the diagnosis of non-small cell lung cancer in a region of high histoplasmosis prevalence. Lung Cancer 36:297–301

    Article  PubMed  Google Scholar 

  6. Cheran SK, Nielsen ND, Patz EF Jr (2004) False-negative findings for primary lung tumors on FDG positron emission tomography: staging and prognostic implications. AJR Am J Roentgenol 182:1129–1132

    Article  PubMed  Google Scholar 

  7. Kavanagh PV, Stevenson AW, Chen MY et al (2004) Nonneoplastic diseases in the chest showing increased activity on FDG PET. AJR Am J Roentgenol 183:1133–1141

    Article  PubMed  Google Scholar 

  8. Sasaki M, Kuwabara Y, Yoshida T et al (2001) Comparison of MET-PET and FDG-PET for differentiation between benign lesions and malignant tumors of the lung. Ann Nucl Med 15:425–431

    Article  PubMed  CAS  Google Scholar 

  9. Kubota K, Matsuzawa T, Fujiwara T et al (1988) Differential diagnosis of solitary pulmonary nodules with positron emission tomography using [11C]L-methionine. J Comput Assist Tomogr 12:794–796

    Article  PubMed  CAS  Google Scholar 

  10. Kubota K, Matsuzawa T, Fujiwara T (1990) Differential diagnosis of lung tumor with positron emission tomography: a prospective study. J Nucl Med 31:1927–1932

    PubMed  CAS  Google Scholar 

  11. Kaira K, Oriuchi N, Otani Y et al (2007) Fluorine-18-alpha-methyltyrosine positron emission tomography for diagnosis and staging of lung cancer: a clinicopathologic study. Clin Cancer Res 13:6369–6378

    Article  PubMed  CAS  Google Scholar 

  12. Schuster DM, Savir-Baruch B, Nieh PT et al (2011) Detection of recurrent prostate carcinoma with anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid PET/CT and 111In–capromab pendetide SPECT/CT. Radiology 259:852–861

    Article  PubMed  Google Scholar 

  13. Schuster DM, Votaw JR, Nieh PT et al (2007) Initial experience with the radiotracer anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid with PET/CT in prostate carcinoma. J Nucl Med 48:56–63

    PubMed  CAS  Google Scholar 

  14. Oka S, Hattori R, Kurosaki F (2007) A preliminary study of anti-1-amino-3-18F-fluorocyclobutyl-1-carboxylic acid for the detection of prostate cancer. J Nucl Med 48:46–55

    PubMed  CAS  Google Scholar 

  15. Shoup TM, Olson J, Hoffman JM et al (1999) Synthesis and evaluation of [18F]1-amino-3-fluorocyclobutane-1-carboxylic acid to image brain tumors. J Nucl Med 40:331–338

    PubMed  CAS  Google Scholar 

  16. Schuster DM, Votaw JR, Halkar RK (2003) Uptake of the synthetic PET amino acid radiotracer 1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (18F-FACBC) within primary and metastic brain cancer compared with 18F-fluorodeoxyglucose (18F-FDG). J Nucl Med 5:167p

    Google Scholar 

  17. Yoshida Y, Oka S, Hattori R et al (2005) Potential of anti-[18F]1-amino-3-fluorocyclobutane-1 carboxylic acid for differentiating between tumor and inflammation in in vitro and in vivo studies. Eur J Nucl Med Mol Imaging 32:S151

    Article  Google Scholar 

  18. McConathy J, Voll RJ, Yu W et al (2003) Improved synthesis of anti-[18F]FACBC: improved preparation of labeling precursor and automated radiosynthesis. Appl Radiat Isot 58:657–666

    Article  PubMed  CAS  Google Scholar 

  19. Plathow C, Weber WA (2008) Tumor cell metabolism imaging. J Nucl Med 49:43S–63S

    Article  PubMed  CAS  Google Scholar 

  20. McConathy J, Yu W, Jarkas N (2012) Radiohalogenated nonnatural amino acids as PET and SPECT tumor imaging agents. Med Res Rev 32:868–905

    Google Scholar 

  21. Schuster D, Votaw J, Nieh P (2007) Initial experience with the radiotracer anti-1-amino-3-F-18-fluorocyclobutane-1-carboxylic acid with PET/CT in prostate carcinoma. J Nucl Med 48:56–63

    PubMed  CAS  Google Scholar 

  22. Kim SJ, Kim YK, Kim IJ (2011) Limited predictive value of dual-time-point F-18 FDG PET/CT for evaluation of pathologic N1 status in NSCLC patients. Clin Nucl Med 36:434–439

    Article  PubMed  Google Scholar 

  23. Nunez R, Kalapparambath A, Varela J (2007) Improvement in sensitivity with delayed imaging of pulmonary lesions with FDG-PET. Rev Esp de Med Nucl 26:196–207

    Article  CAS  Google Scholar 

  24. Yamada Y, Uchida Y, Tatsumi K et al (1998) Fluorine-18-fluorodeoxyglucose and carbon-11-methionine evaluation of lymphadenopathy in sarcoidosis. J Nucl Med 39:1160–1166

    PubMed  CAS  Google Scholar 

  25. Nettelbladt OS, Sundin AE, Valind SO (1998) Combined fluorine-18-FDG and carbon-11-methionine PET for diagnosis of tumors in lung and mediastinum. J Nucl Med 39:640–647

    PubMed  CAS  Google Scholar 

  26. Nye JA, Schuster DM, Yu W et al (2007) Biodistribution and Radiation dosimetry of the synthetic nonmetabolized amino acid analogue anti-18F-FACBC in humans. J Nucl Med 48:1017–1020

    Article  PubMed  CAS  Google Scholar 

  27. Deloar HM, Fujiwara T, Nakamura T et al (1998) Estimation of internal absorbed dose of l-[methyl-11C]methionine using whole-body positron emission tomography. Eur J Nucl Med 25:629–633

    Article  PubMed  CAS  Google Scholar 

  28. Inoue T, Tomiyoshi K, Higuichi T (1998) Biodistribution studies on l-3-[fluorine-18]fluoro-alpha-methyl tyrosine: a potential tumor-detecting agent. J Nucl Med 39:663–667

    PubMed  CAS  Google Scholar 

  29. Martarello L, McConathy J, Camp VM (2002) Synthesis of syn- and anti-1-amino-3-[18F]fluoromethyl-cyclobutane-1-carboxylic acid (FMACBC), potential PET ligands for tumor detection. J Med Chem 45:2250–2259

    Article  PubMed  CAS  Google Scholar 

  30. McConathy J, Martarello L, Simpson NE (2002) Uptake profiles of six 18F-labeled amino acids for tumor imaging: comparison of in vitro and in vivo uptake of branched chain and cyclobutyl amino acids by 9L gliosarcoma tumor cells. J Nucl Med 43(5):41P

    Google Scholar 

  31. Okudaira H, Shikano N, Nishii R et al (2011) Putative transport mechanism and intracellular fate of trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid in human prostate cancer. J Nucl Med 52:822–829

    Article  PubMed  CAS  Google Scholar 

  32. Oka S, Okudaira H, Yoshida Y (2012) Transport mechanisms of trans-1-amino-3-fluoro[1-(14)C]cyclobutanecarboxylic acid in prostate cancer cells. Nucl Med Biol 39:109–119

    Article  PubMed  CAS  Google Scholar 

  33. Fuchs BC, Bode BP (2005) Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime? Semin in Cancer Biol 15:254–266

    Article  CAS  Google Scholar 

  34. Takeuchi K, Ogata S, Nakanishi K (2010) LAT1 expression in non-small-cell lung carcinomas: analyses by semiquantitative reverse transcription-PCR (237 cases) and immunohistochemistry (295 cases). Lung Cancer 68:58–65

    Article  PubMed  Google Scholar 

  35. Suzawa N, Ito M, Qiao S (2011) Assessment of factors influencing FDG uptake in non-small cell lung cancer on PET/CT by investigating histological differences in expression of glucose transporters 1 and 3 and tumour size. Lung Cancer 72:191–198

    Article  PubMed  Google Scholar 

  36. Schuster DM, Savir-Baruch B, Nieh PT et al (2010) Report of a clinical trial of anti 1 amino 3 [18F]fluorocyclobutane-1-carboxylic acid (anti-[18F]FACBC) PET-CT in recurrent prostate carcinoma. J Nucl Med 51:127P

    Google Scholar 

  37. Martin B, Paesmans M, Mascaux C (2004) Ki-67 expression and patient's survival in lung cancer: systematic review of the literature with meta-analysis. Br J Cancer 91:2018–2025

    Article  PubMed  CAS  Google Scholar 

  38. Haga Y, Hiroshima K, Iyoda A (2003) Ki-67 expression and prognosis for smokers with resected stage in non–small cell lung cancer. Ann Thorac Surg 75:1727–1732

    Article  PubMed  Google Scholar 

  39. Vesselle H, Schmidt RA, Pugsley JM et al (2000) Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography. Clin Cancer Res 6:3837–3844

    PubMed  CAS  Google Scholar 

  40. Van Baardwijk A, Dooms C, van Suylen RJ et al (2007) The maximum uptake of 18F-deoxyglucose on positron emission tomography scan correlates with survival, hypoxia inducible factor-1α and GLUT-1 in non-small cell lung cancer. Eur J Cancer 43:1392–1398

    Article  PubMed  Google Scholar 

  41. Chung JK, Lee YJ, Kim SK et al (2004) Comparison of [18F]fluorodeoxyglucose uptake with glucose transporter-1 expression and proliferation rate in human glioma and non-small-cell lung cancer. Nucl Med Commun 25:11–17

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was sponsored by Nihon Medi-Physics Co., Ltd. We acknowledge the hard work of Delicia Votaw, CNMT; Fenton G. Ingram, RT, CNMT, PET; Seraphinah Lawal,(R), CNMT, PET; Adam Brown, RT (N), CNMT; Ronald J. Crowe, RPh, BCNP; the entire cyclotron and synthesis team; James R. Galt, PhD, John R. Votaw, PhD, and Rabih Bechara, MD. We also gratefully acknowledge the contributions of Eric Jablonowski, AA, for media support.

Conflict of Interest

One of the authors; Dr. Mark Goodman and Emory University are eligible for royalties from the use of the radio tracer (anti 3-[18F]FACBC) being studied.

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Correspondence to David M. Schuster.

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Research support: Nihon Medi-Physics Co.,Ltd.

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Amzat, R., Taleghani, P., Miller, D.L. et al. Pilot Study of the Utility of the Synthetic PET Amino-Acid Radiotracer Anti-1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid for the Noninvasive Imaging of Pulmonary Lesions. Mol Imaging Biol 15, 633–643 (2013). https://doi.org/10.1007/s11307-012-0606-7

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