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. 2017 Aug 28;14(5):5279–5284. doi: 10.3892/ol.2017.6840

Mismatched intratumoral distribution of [18F] fluorodeoxyglucose and 3′-deoxy-3′-[18F] fluorothymidine in patients with lung cancer

Xiangcheng Wang 1,2, Yulin He 1, Weina Zhou 1, Xia Bai 1, Yiwei Wu 2,✉, Xuemei Wang 1, Xiao-Feng Li 3,4
PMCID: PMC5652252  PMID: 29098026

Abstract

In a mouse model of human lung cancer, intratumoral distribution between 3′-deoxy-3′-[18F] fluorothymidine (18F-FLT) and [18F] fluorodeoxyglucose (18F-FDG) was mutually exclusive. 18F-FLT primarily accumulated in proliferating cancer cells, whereas 18F-FDG accumulated in hypoxic cancer cells. The aim of the present study was to evaluate these preclinical findings in patients with lung cancer. A total of 55 patients with solitary pulmonary lesion were included in the present study. Patients underwent 18F-FLT positron emission tomography-computed tomography (PET/CT) and 18F-FDG PET/CT scan with a 3-day interval. The final diagnosis was based on histological examination. Among the 55 cases, a total of 24 cases were confirmed as malignant lesions. Mismatched 18F-FLT- and 18F-FDG-accumulated regions were observed in 19 cases (79%) and matched in 5 (21%). Among the 31 benign lesions, 18F-FLT and 18F-FDG were mismatched in 12 cases (39%) and matched in 19 (61%). The difference in intratumoral distribution of 18F-FLT and 18F-FDG between malignant and benign lesions was statistically significant (P<0.05). The results of the present study indicate that a mismatch in intratumoral distribution of 18F-FLT and 18F-FDG may be a feature of patients with lung cancer. Increased 18F-FDG accumulation may serve as an indicator of tumor hypoxia, whereas regions with increased 18F-FLT uptake may be associated with an increased rate of cancer cell proliferation in patients with lung cancer.

Keywords: lung cancer, [18F] fluorodeoxyglucose, 3′-deoxy-3′-[18F] fluorothymidine, positron emission tomography-computed tomography

Introduction

Positron emission tomography (PET) is widely used for cancer detection, staging and monitoring the response to therapy. [18F] fluorodeoxyglucose (18F-FDG) and 3′-deoxy-3′-[18F] fluorothymidine (18F-FLT) are commonly used PET tracers for imaging glucose metabolism and cell proliferation, respectively (1–12). In a mouse model of human lung cancer, it has been previously demonstrated that intratumoral distribution between 18F-FLT and 18F-FDG was mutually exclusive. 18F-FLT accumulated primarily in proliferating cancer cells, whereas 18F-FDG accumulated in hypoxic cancer cells that are less proliferative (13–16). To the best of our knowledge, intratumoral distribution of 18F-FLT and 18F-FDG in patients with lung cancer has not been previously reported.

Differential diagnosis of malignant pulmonary lesions may be challenging. Computed tomography (CT) is the method of choice for the diagnosis of pulmonary lesions. PET/CT imaging reflects the biological and metabolic aspects of pulmonary lesions (17). 18F-FDG PET/CT has been widely used for the diagnosis of pulmonary lesions; however, false-negative as well as false-positive results are frequently observed (17,18). 18F-FLT is a positron radioactive tracer that reflects cancer cell proliferation. Therefore, 18F-FLT may be a useful tool for the diagnosis of pulmonary lesions (19).

In the present study, it was hypothesized that the mutually exclusive distribution pattern between 18F-FLT and 18F-FDG described in animal tumor models may apply to patients with lung malignancies as well. To examine this hypothesis, patients with pulmonary lesions that initially underwent a 18F-FDG PET/CT scan and subsequently a 18F-FLT PET/CT scan were studied.

Materials and methods

Patients

The present study was approved by the Institutional Review Boards of the Inner Mongolia Medical University (Hohhot, China) and the Soochow Medical University (Jiangsu, China). Written informed consent was obtained from all patients prior to participation. The Institutional Review Board of the University of Louisville (Louisville, KY, USA) approved data transfer and use. From June 2013 to August 2015, a total of 55 patients (Table I) with pretreated lung lesions were recruited to the present study (31 males and 24 females; age range, 17–68 years). Histological examination of the lesions was performed in every patient. The diameter of the lesions ranged between 8 and 50 mm.

Table I.

Patients' clinical data and PET/CT results.

Patient no. Age/sex SUVmax FDG/FLT Pathological diagnosis FDG/FLT PET/CT SUVmax
  1 55/F 5.3/2.7 Adenocarcinoma Mismatch
  2 48/F 3.5/1.4 Tuberculoma Match
  3 61/F 4.2/2.1 Squamous carcinoma Match
  4 65/F 2.8/1.1 Tuberculoma Mismatch
  5 59/F 2.3/1.0 Organizing pneumonia Match
  6 63/F 5.8/2.1 Adenocarcinoma Mismatch
  7 60/F 2.3/1.2 Tuberculoma Mismatch
  8 62/F 4.8/2.2 Adenocarcinoma Mismatch
  9 64/F 3.2/2.0 Adenocarcinoma Mismatch
10 64/F 1.6/0.9 Tuberculoma Mismatch
11 67/F 1.9/0.9 Hamartoma Match
12 49/F 2.1/1.5 Tuberculoma Match
13 57/F 3.8/2.8 Adenocarcinoma Mismatch
14 59/F 4.1/2.6 Adenocarcinoma Mismatch
15 47/F 2.0/1.4 Tuberculoma Match
16 49/M 2.6/1.6 Tuberculoma Mismatch
17 53/M 3.7/2.4 Adenocarcinoma Mismatch
18 60/M 7.9/2.8 Squamous carcinoma Match
19 65/M 1.5/0.9 Organizing pneumonia Match
20 67/M 3.5/2.0 Inflammatory pseudotumor Mismatch
21 57/M 6.8/2.4 Squamous carcinoma Match
22 60/M 3.7/2.6 Squamous carcinoma Match
23 58/M 4.2/2.0 Squamous carcinoma Mismatch
24 62/M 3.6/2.5 Adenocarcinoma Mismatch
25 63/M 3.4/2.6 Adenocarcinoma Mismatch
26 66/M 1.8/1.0 Inflammatory pseudotumor Mismatch
27 45/M 1.6/1.3 Tuberculoma Mismatch
28 59/M 2.6/1.2 Tuberculoma Match
29 17/M 2.9/1.5 Tuberculoma Match
30 48/M 3.0/1.8 Squamous carcinoma Mismatch
31 62/M 1.1/1.0 Tuberculoma Match
32 62/M 2.4/1.6 Tuberculoma Match
33 62/M 2.1/0.8 Organizing pneumonia Mismatch
34 50/M 3.1/0.9 Tuberculoma Match
35 52/M 1.5/1.0 Hamartoma Match
36 57/M 3.6/2.2 Adenocarcinoma Mismatch
37 54/M 3.2/1.9 Adenocarcinoma Mismatch
38 52/M 1.6/0.7 Tuberculoma Match
39 44/M 1.0/0.7 Hamartoma Mismatch
40 49/M 5.4/1.8 Squamous carcinoma Mismatch
41 62/M 1.5/0.7 Tuberculoma Match
42 68/M 3.5/2.0 Adenocarcinoma Mismatch
43 47/F 4.1/1.1 Tuberculoma Match
44 49/M 3.1/1.4 Tuberculoma Match
45 58/M 6.8/2.4 Squamous carcinoma Mismatch
46 60/M 2.6/1.1 Tuberculoma Mismatch
47 67/M 8.2/3.5 Adenocarcinoma Mismatch
48 55/F 3.2/1.8 Adenocarcinoma Match
49 48/F 1.5/1.0 Organizing pneumonia Mismatch
50 61/F 5.8/2.5 Adenocarcinoma Mismatch
51 65/F 2.7/2.1 Adenocarcinoma Mismatch
52 59/F 1.9/0.8 Inflammatory pseudotumor Match
53 63/F 1.6/0.8 Hamartoma Mismatch
54 60/F 1.8/1.1 Inflammatory pseudotumor Match
55 62/F 1.5/0.9 Hamartoma Match
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PET/CT, positron emission tomography-computed tomography; FLT, 3′-deoxy-3′-[18F]fluorothymidine; FDG, [18F]fluorodeoxyglucose; SUVmax, maximal standardized update value; F, female; M, male.

Radiopharmaceuticals

[18F] fluoride was generated in-house using a cyclotron. 18F-FDG and 18F-FLT were synthesized automatically using FX-FN conventional modules at the PET/CT facility of the Inner Mongolia Medical University (Hohhot, China). 18F-FDG and 18F-FLT were pyrogen-free and qualified for clinical use, with radiochemical purity >98%.

PET/CT imaging protocol

PET/CT images were obtained using a GE Discovery ST PET/CT scanner. Prior to 18F-FDG PET scanning, patients were instructed to fast for >6 h and their blood glucose levels were determined to be <6 mmol/l. Whole body 18F-FDG PET/CT scans were performed 1 h after intravenous administration of 3.7 MBq/kg 18F-FDG. Subsequently, 3 days after 18F-FDG imaging, local thoracic 18F-FLT PET/CT scans were performed, 1 h after the injection of 18F-FLT (3.7 MBq/kg). Spiral CT scans (voltage, 120 kV; current, 160–220 mA) were conducted for attenuation correction and anatomy referral.

A board of three certified physicians in nuclear medicine assessed the PET/CT images. Visual analysis to score lesion radioactivity uptake of each tracer was performed (20). The maximal standardized uptake value (SUVmax) was used to spatially compare the intralesional distribution of 18F-FDG and 18F-FLT.

Histological examination of the lesions was performed for all patients by board-certified pathologists at the Department of Pathology (Affiliated Hospital of Inner Mongolian Medical University). Routine hematoxylin and eosin (H&E) staining was performed. Briefly, slides containing 5 µm paraffin sections were placed on a slide holder, deparaffinized and rehydrated. Sections were treated with hematoxylin solution, dipped 8–12 times in acid ethanol to destain, and stained for 30 sec with eosin. H&E stain imaging was developed with a light microscope at ×100 magnification.

Statistical analysis

SPSS software (version 17.0; SPSS, Inc., Chicago, IL, USA) was used to analyze the data using a χ2 test. P<0.05 was considered to indicate a statistically significant difference.

Results

The clinical information and PET/CT results of the patient cohort are summarized in Table I. Among the 55 cases, 24 lesions were confirmed as primary lung malignancies (16 cases with adenocarcinoma, 8 cases with squamous cell carcinoma) and 31 lesions were benign (18 cases with tuberculosis, 5 with hamartoma, 4 with inflammatory pseudo-tumor and 4 with organizing pneumonia).

Spatial intratumoral distribution of 18F-FLT and 18F-FDG mismatched in 19/24 malignant lesions (79%) and matched in 5 (21%). Fig. 1 presents an apparent mismatch in intratumoral distribution of 18F-FLT and 18F-FDG in a 67-year-old male patient with pretreated lung adenocarcinoma. Increased 18F-FDG uptake combined with decreased 18F-FLT accumulation in a patient with squamous carcinoma is presented in Fig. 2. Intratumoral distribution of 18F-FLT and 18F-FDG in lung malignancies was identified to be mainly heterogeneous and mutually excluded.

Figure 1.

Figure 1.

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Scan images of a 67-year-old male patient with pretreated adenocarcinoma (39×23 mm) in the right middle lobe of the lung. An 18F-FLT PET/CT scan was performed 3 days after an 18F-FDG scan. (A) 18F-FDG PET/CT scan image. (B) 18F-FLT PET/CT scan image. (C) CT scan providing additional anatomical information. (D) Enlarged 18F-FDG scan image of the area indicated by the arrow. (E) Enlarged 18F-FLT scan image of the area indicated by the arrow. (F) Hematoxylin and eosin staining indicated lung adenocarcinoma. PET/CT, positron emission tomography-computed tomography; 18F-FLT, 3′-deoxy-3′-[18F] fluorothymidine; 18F-FDG, [18F] fluorodeoxyglucose; R, right.

Figure 2.

Figure 2.

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Scan images of a 49-year-old male patient with pretreated squamous carcinoma (30×17 mm) in the left upper lobe in the lung. An 18F-FLT PET/CT scan was performed 3 days after an 18F-FDG scan. (A) 18F-FDG PET/CT scan image. (B) 18F-FLT PET/CT scan image. (C) CT scan providing additional anatomical information. (D) Enlarged 18F-FDG scan image of the area indicated by the arrow. (E) Enlarged 18F-FLT scan image of the area indicated by the arrow. (F) Hematoxylin and eosin staining indicated squamous carcinoma. PET/CT, positron emission tomography-computed tomography; 18F-FLT, 3′-deoxy-3′-[18F] fluorothymidine; 18F-FDG, [18F] fluorodeoxyglucose; R, right.

Regarding the 31 benign lesions, intralesional mismatched distribution of 18F-FLT and 18F-FDG was observed in 12 cases (39%). Fig. 3 presents scan images of mismatched 18F-FLT and 18F-FDG intralesional distribution in a 49-year-old male patient with lung tuberculoma. Matched intralesional distribution of 18F-FLT and 18F-FDG was observed in 19/31 benign lesions (61%). An indicative example of a patient with an inflammatory pseudotumor demonstrating negative 18F-FLT and positive 18F-FDG PET scans is presented in Fig. 4.

Figure 3.

Figure 3.

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Scan images of a 49-year-old male patient with untreated tuberculoma (13×18 mm) in the right upper lobe in the lung. An 18F-FLT PET/CT scan was performed 3 days after an 18F-FDG scan. (A) 18F-FDG PET/CT scan image. (B) 18F-FLT PET/CT scan image. (C) CT scan providing additional anatomical information. (D) Enlarged 18F-FDG scan image of the area indicated by the arrow. (E) Enlarged 18F-FLT scan image of the area indicated by the arrow. (F) Hematoxylin and eosin staining indicated tuberculoma. PET/CT, positron emission tomography-computed tomography; 18F-FLT, 3′-deoxy-3′-[18F] fluorothymidine; 18F-FDG, [18F] fluorodeoxyglucose; R, right.

Figure 4.

Figure 4.

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Scan images of a 59-year-old female patient with inflammatory pseudotumor (50×40 mm) in the right upper lobe in the lung. An 18F-FLT PET/CT scan was performed 2 days after an 18F-FDG scan. (A) 18F-FDG PET/CT scan image. (B) 18F-FLT PET/CT scan image. (C) CT scan providing additional anatomical information. (D) Enlarged 18F-FDG scan image of the area indicated by the arrow. (E) Enlarged 18F-FLT scan image of the area indicated by the arrow. (F) Hematoxylin and eosin staining indicated inflammatory pseudotumor. PET/CT, positron emission tomography-computed tomography; 18F-FLT, 3′-deoxy-3′-[18F] fluorothymidine; 18F-FDG, [18F] fluorodeoxyglucose; R, right.

These results indicate that mismatched intralesional accumulation of 18F-FLT and 18F-FDG was more frequently observed in malignant compared with benign lung lesions. The difference in intralesional distribution of 18F-FLT and 18F-FDG between malignant and benign lesions was statistically significant (P<0.05).

Discussion

It has previously been reported based on studies using mouse non-small cell lung cancer models that 18F-FDG accumulates in hypoxic regions, whereas 18F-FLT accumulates in well-oxygenated proliferating cells. Additionally, it has been demonstrated that the intratumoral distribution of 18F-FDG and 18F-FLT is mutually exclusive (13,14). In the present study, the association between 18F-FDG and 18F-FLT uptake was further elucidated in patients with lung cancer.

In the present study, it was demonstrated that intratumoral 18F-FDG and 18F-FLT accumulation is mutually exclusive. It was observed that regions with increased 18F-FDG accumulation were mainly associated with decreased 18F-FLT uptake. This is consistent with previous preclinical results in mouse lung cancer models (13–16). Intratumoral heterogeneity of 18F-FDG and 18F-FLT accumulation reflected the heterogeneous distribution of hypoxic (increased 18F-FDG uptake) and highly proliferative (increased 18F-FLT uptake) cancer cells; in agreement with previously reported preclinical results (13–16).

18F-FDG PET/CT is widely used in clinical practice for the detection of malignancies. However, it is not a cancer-specific tracer as it accumulates in hypoxic tissues regardless of malignant phenotype (10,13,15). Even though benign lesions present mainly low 18F-FDG uptake, in certain cases increased 18F-FDG accumulation is observed in inflammatory diseases including tuberculosis. Activated macrophages and other inflammatory cells may result in enhanced 18F-FDG accumulation in benign conditions including pneumonia, bronchiectasis, pulmonary tuberculosis, fungal infections, sarcoidosis, histoplasmosis and granuloma (21,22). Macrophages and other inflammatory cells, frequently observed in necrotic regions of inflammatory lesions, accumulate increased levels of 18F-FDG possibly due to the hypoxic microenvironment (23).

In the present study, 18F-FDG and 18F-FLT PET/CT scan uptake, performed with a 3-day interval, were compared in patients with lung lesions. A mismatch in the intralesional 18F-FLT and 18F-FDG accumulation was observed particularly in lung malignancies compared with benign lesions (Table I). Therefore, on the basis of the results of the present study, it is suggested that this mismatch may serve as an indicator of lung malignancy.

In well-differentiated slow-growing tumors, including bronchiole alveolar carcinomas, false-negative 18F-FDG PET results have been reported (20,24). This may be attributed to to the absence of hypoxic microenvironment of slow-growing malignancies“18F-FDG is mainly considered as a hypoxia-specific rather than a tumor avid tracer (13,15,16). This explains why 18F-FDG exhibited relatively low specificity in distinguishing malignant from benign lesions.

It has been demonstrated that the combination of 18F-FLT and 18F-FDG, either as separate PET scans performed on subsequent days or as one scan using a 18F-FLT and 18F-FDG cocktail, may be superior to an 18F-FDG scan for accurate disease detection (14). 18F-FDG mainly accumulates in hypoxic regions, whereas 18F-FLT accumulates in highly proliferating cells (6,7,13,14). The use of 18F-FLT and 18F-FDG cocktail PET may have an advantage compared with individual tracer PET. A clinical trial for 18F-FLT and 18F-FDG cocktail PET scanning for cancer detection and management is currently underway (25).

The results of the present study demonstrate that mismatched intratumoral distribution of 18F-FLT and 18F-FDG is a common feature of patients with lung cancer and may serve as an indicator of lung malignancy.

Acknowledgements

The authors would like to thank Dr Cheng Wang, Mr. Baoliang Bao and Dr Chunmei Wang (Department of Nuclear Medicine, Affiliated Hospital of Inner Mongolian Medical University, Hohhot, China) for their technical assistance. The present study was supported by the Natural Science Foundation of Inner Mongolia (grant no. 2013MS1188), the Scientific Research Project of the Affiliated Hospital of Inner Mongolian Medical University (grant no. 2014NYFYYB008), the Inner Mongolian Major Basic Science Research Program (grant no. 201503001) and the Inner Mongolian Science and Technology Innovation Project (grant no. 2015cztcxyd03). Part of the present study was presented at The Society of Nuclear Medicine and Molecular Imaging 2015 Annual Meeting (Baltimore, MD, USA; 4–10 June 2015) (26).

References

  • 1.Herrmann K, Erkan M, Dobritz M, Schuster T, Siveke JT, Beer AJ, Wester HJ, Schmid RM, Friess H, Schwaiger M, et al. Comparison of 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography (FLT PET) and FDG PET/CT for the detection and characterization of pancreatic tumours. Eur J Nucl Med Mol Imaging. 2012;39:846–851. doi: 10.1007/s00259-012-2061-8. [DOI] [PubMed] [Google Scholar]
  • 2.Nakajo M, Nakajo M, Kajiya Y, Jinguji M, Mori S, Aridome K, Suenaga T, Tanaka S. High FDG and low FLT Uptake in a thyroid papillary carcinoma incidentally discovered by FDG PET/CT. Clin Nucl Med. 2012;37:607–608. doi: 10.1097/RLU.0b013e318252d80f. [DOI] [PubMed] [Google Scholar]
  • 3.Zander T, Scheffler M, Nogova L, Kobe C, Engel-Riedel W, Hellmich M, Papachristou I, Toepelt K, Draube A, Heukamp L, et al. Early prediction of nonprogression in advanced non-small-cell lung cancer treated with erlotinib by using [(18)F]fluorodeoxyglucose and [(18)F]fluorothymidine positron emission tomography. J Clin Oncol. 2011;29:1701–1708. doi: 10.1200/JCO.2010.32.4939. [DOI] [PubMed] [Google Scholar]
  • 4.Frings V, de Langen AJ, Smit EF, van Velden FH, Hoekstra OS, van Tinteren H, Boellaard R. Repeatability of metabolically active volume measurements with 18F-FDG and 18F-FLT PET in non-small cell lung cancer. J Nucl Med. 2010;51:1870–1877. doi: 10.2967/jnumed.110.077255. [DOI] [PubMed] [Google Scholar]
  • 5.Yang W, Zhang Y, Fu Z, Yu J, Sun X, Mu D, Han A. Imaging of proliferation with 18F-FLT PET/CT versus 18F-FDG PET/CT in non-small-cell lung cancer. Eur J Nucl Med Mol Imaging. 2010;37:1291–1299. doi: 10.1007/s00259-010-1412-6. [DOI] [PubMed] [Google Scholar]
  • 6.Yamamoto Y, Nishiyama Y, Ishikawa S, Nakano J, Chang SS, Bandoh S, Kanaji N, Haba R, Kushida Y, Ohkawa M. Correlation of 18F-FLT and 18F-FDG uptake on PET with Ki-67 immunohistochemistry in non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2007;34:1610–1616. doi: 10.1007/s00259-007-0449-7. [DOI] [PubMed] [Google Scholar]
  • 7.Buck AK, Halter G, Schirrmeister H, Kotzerke J, Wurziger I, Glatting G, Mattfeldt T, Neumaier B, Reske SN, Hetzel M. Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG. J Nucl Med. 2003;44:1426–1431. [PubMed] [Google Scholar]
  • 8.Burgman P, O'Donoghue JA, Humm JL, Ling CC. Hypoxia-induced increase in FDG uptake in MCF7 cells. J Nucl Med. 2001;42:170–175. [PubMed] [Google Scholar]
  • 9.Pugachev A, Ruan S, Carlin S, Larson SM, Campa J, Ling CC, Humm JL. Dependence of FDG uptake on tumor microenvironment. Int J Radiat Oncol Biol Phys. 2005;62:545–553. doi: 10.1016/j.ijrobp.2005.02.009. [DOI] [PubMed] [Google Scholar]
  • 10.Li XF, Ma Y, Sun X, Humm JL, Ling CC, O'Donoghue JA. High 18F-FDG uptake in microscopic peritoneal tumors requires physiologic hypoxia. J Nucl Med. 2010;51:632–638. doi: 10.2967/jnumed.109.071233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Dence CS, Ponde DE, Welch MJ, Lewis JS. Autoradiographic and small-animal PET comparisons between (18)F-FMISO, (18)F-FDG, (18)F-FLT and the hypoxic selective (64)Cu-ATSM in a rodent model of cancer. Nucl Med Biol. 2008;35:713–720. doi: 10.1016/j.nucmedbio.2008.06.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Mudd SR, Holich KD, Voorbach MJ, Cole TB, Reuter DR, Tapang P, Bukofzer G, Chakravartty A, Donawho CK, Palma JP, et al. Pharmacodynamic evaluation of irinotecan therapy by FDG and FLT PET/CT imaging in a colorectal cancer xenograft model. Mol Imaging Biol. 2012;14:617–624. doi: 10.1007/s11307-011-0529-8. [DOI] [PubMed] [Google Scholar]
  • 13.Huang T, Civelek AC, Li J, Jiang H, Ng CK, Postel GC, Shen B, Li XF. Tumor microenvironment-dependent 18F-FDG, 18F-fluorothymidine, and 18F-misonidazole uptake: A pilot study in mouse models of human non-small cell lung cancer. J Nucl Med. 2012;53:1262–1268. doi: 10.2967/jnumed.111.098087. [DOI] [PubMed] [Google Scholar]
  • 14.Li XF, Huang T, Jiang H, Wang X, Shen B, Wang X, Ng CK, Postel GC, Civelek AC. Combined injection of (18)F-fluorodeoxyglucose and 3′-Deoxy-3′-[(18)F]fluorothymidine PET achieves more complete identification of viable lung cancer cells in mice and patients than individual radiopharmaceutical: A proof-of-concept study. Transl Oncol. 2013;6:775–783. doi: 10.1593/tlo.13577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Li XF, Du Y, Ma Y, Postel GC, Civelek AC. (18)F-fluorodeoxyglucose uptake and tumor hypoxia: Revisit (18)F-fluorodeoxyglucose in oncology application. Transl Oncol. 2014;7:240–247. doi: 10.1016/j.tranon.2014.02.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Zhang G, Li J, Wang X, Ma Y, Yin X, Wang F, Zheng H, Duan X, Postel GC, Li XF. The reverse Warburg effect and 18F-FDG uptake in non-small cell lung cancer A549 in mice: A pilot study. J Nucl Med. 2015;56:607–612. doi: 10.2967/jnumed.114.148254. [DOI] [PubMed] [Google Scholar]
  • 17.Bunyaviroch T, Coleman RE. PET evaluation of lung cancer. J Nucl Med. 2006;47:451–469. [PubMed] [Google Scholar]
  • 18.Graves EE, Maity A, Le QT. The tumor microenvironment in non-small-cell lung cancer. Semin Radiat Oncol. 2010;20:156–163. doi: 10.1016/j.semradonc.2010.01.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Vesselle H, Grierson J, Muzi M, Pugsley JM, Schmidt RA, Rabinowitz P, Peterson LM, Vallières E, Wood DE. In vivo validation of 3′deoxy-3′-[(18)F]fluorothymidine ([(18)F]FLT) as a proliferation imaging tracer in humans: Correlation of [(18)F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors. Clin Cancer Res. 2002;8:3315–3323. [PubMed] [Google Scholar]
  • 20.Tian J, Yang X, Yu L, Chen P, Xin J, Ma L, Feng H, Tan Y, Zhao Z, Wu W. A multicenter clinical trial on the diagnostic value of dual-tracer PET/CT in pulmonary lesions using 3′-deoxy-3′-18F-fluorothymidine and 18F-FDG. J Nucl Med. 2008;49:186–194. doi: 10.2967/jnumed.107.044966. [DOI] [PubMed] [Google Scholar]
  • 21.van Waarde A, Cobben DC, Suurmeijer AJ, Maas B, Vaalburg W, de Vries EF, Jager PL, Hoekstra HJ, Elsinga PH. Selectivity of 18F-FLT and 18F-FDG for differentiating tumor from inflammation in a rodent model. J Nucl Med. 2004;45:695–700. [PubMed] [Google Scholar]
  • 22.Grierson JR, Shields AF. Radiosynthesis of 3′-deoxy-3′-[(18)F]fluorothymidine: [(18)F]FLT for imaging of cellular proliferation in vivo. Nucl Med Biol. 2000;27:143–156. doi: 10.1016/S0969-8051(99)00104-3. [DOI] [PubMed] [Google Scholar]
  • 23.Tarkin JM, Joshi FR, Rudd JH. PET imaging of inflammation in atherosclerosis. Nat Rev Cardiol. 2014;11:443–457. doi: 10.1038/nrcardio.2014.80. [DOI] [PubMed] [Google Scholar]
  • 24.Higashi K, Ueda Y, Seki H, Yuasa K, Oguchi M, Noguchi T, Taniguchi M, Tonami H, Okimura T, Yamamoto I. Fluorine-18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma. J Nucl Med. 1998;39:1016–1020. [PubMed] [Google Scholar]
  • 25.Kurdziel K, Ravizzini G, Croft B, Tatum J, Choyke P, Kobayashi H. The evolving role of nuclear molecular imaging in cancer. Expert Opin Med Diagn. 2008;2:829–842. doi: 10.1517/17530059.2.7.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Wang X, Wang X, Zhao Z, Li XF. The mismatched intratumoral distribution of 18F-FLT and 18F-FDG may be a better indicator of malignancy: A PET/CT study in patients with solitary pulmonary nodule. J Nucl Med. 2015;56(Suppl 3):S124. [Google Scholar]

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