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Table 1 Summary of clinical studies evaluating diagnosis and staging and their findings in lung cancer based on [18F]FLT-PET proliferative imaging

From: Clinical value of 3'-deoxy-3'-[18F]fluorothymidine-positron emission tomography for diagnosis, staging and assessing therapy response in lung cancer

Reference

n

[18F]FLT/[18F]FDG LC primary Tumour uptake (SUV)

[18F]FLT/[18F]FDG different LC histotypes uptake (SUVmax)

Purpose

TNM stage

Reference standard

Findings

Buck et al. 2002 [16]

30

Mean SUVmax = 5.2

SCLC (n = 1): 2.4

Diagnosis

TxN0M0 (n = 1); TxN0M1 (n = 4); T1N0M0 (n = 2); T1N1M0 (n = 2); T2N0M0 (n = 1); T2bN0M0 (n = 1); T2N1M0 (n = 4); T2N2Mx (n = 1); T2N2M1 (n = 1); T3N0M0 (n = 1); T3N3M0 (n = 1); T4N1M0 (n = 1); T4N2M0 (n = 2)

Histopathology

Ki-67

[18F]FLT uptake was weak but easily detectable in Primary lesions. [18F]FLT is strongly correlated with Ki-67 in the malignant lesions

Vesselle et al. 2002 [27]

10

SUVmean: 3.84

LCC (n = 4): 5.29

SqCC (n = 3): 3.58

ADC (n = 2): 4.01

Diagnosis

NA

Histopathology

Ki-67

S-phase fraction (SPF)

[18F]FLT SUVmax was correlated with Ki-67 and SPF (r = 0.78, p = 0.0043) and (r = 0.69, p = 0.03), respectively

Dittmann et al. 2003 [23]

16

[18F]FLT SUVmean: 4.0 [18F]FDG SUVmean: 6.9

NA

Diagnosis

NA

Histopathology

Ki-67

[18F]FDG

[18F]FDG uptake was significantly higher than [18F]FLT uptake (p = 0.0006). [18F]FLT accurately detected thoracic lesions. Detection of lesions in the liver and the bone marrow was hampered with high physiological [18F]FLT uptake

Buck et al. 2003 [22]

26

[18F]FLT SUVmean: 1.8 [18F]FDG SUVmean: 4.1

[18F]FLT: SCLC (N = 1): 2.4

[18F]FDG: SCLC (N = 1): 12.7

Diagnosis

TxN0M0 (n = 1); TxN0M1 (n = 4); T1N0M0 (n = 1); T1N1M0 (n = 2); T2bN0M0 (n = 1); T2N1M0 (n = 4); T2N2Mx (n = 1); T3N0M0 (n = 1); T3N3M0 (n = 1); T4N2M0 (n = 2)

Histopathology

Ki-67

[18F]FDG

[18F]FDG uptake was significantly higher than [18F]FLT uptake (p = 0.05)

Cobben et al. 2004 [15]

17

[18F]FLT Median SUVmax: 2.7

[18F]FDG Median SUVmax: 8

[18F]FLT: ADC (n = 4): 2.73

SqCC (n = 4): 2.55

[18F]FDG: ADC (n = 4): 7.38

SqCC (n = 4) = 9.83

Diagnosis

Staging

TxN2/3M1 (n = 1);

T1N0M1 (n = 1);

T2N0M0 (n = 1); T2N2M0 (n = 1); T2N2M1 (n = 1); T2N2/3M1 (n = 1); T2N3M1 (n = 1);

T4N0M1 (n = 2); T4N1M1 (n = 1); T4N2M0 (n = 3); T4N2M1 (n = 3)

Histopathology

[18F]FDG

[18F]FDG uptake was significantly higher than [18F]FLT uptake (p = 0.012).. Staging by [18F]FLT-PET was correct for 8 of 17 patients

Buck et al. 2005 [17]

47

[18F]FLT SUVmean: 3.7

[18F]FLT SUVmax: 5.5 [18F]FDG SUVmean: 6

[18F]FDG SUVmax: 11

[18F]FLT: ADC (n = 8): 4.34

SqCC (n = 6): 6

LCC (n = 1): 5.7

SCLC (n = 1): 2.4

[18F]FDG: ADC (n = 8): 8.11

SqCC (n = 6): 6.5

LCC (n = 1): 12.5

SCLC (n = 1): 12.7

Diagnosis

Staging

TcisN0M0 (n = 1);

T1N0M0 (n = 2); T1N1M0 (n = 2); T1N3M0 (n = 1); T2N0M0 (n = 2);

T2N1M0 (n = 5); T2N2M0 (n = 2);

T3N0M0 (n = 1); T3N3M0 (n = 1);

T4N1M0 (n = 1); T4N2M0 (n = 2); T4N3M0 (n = 1)

Histopathology

[18F]FDG

[18F]FDG uptake was significantly higher than [18F]FLT uptake (p = 0.05). Clinical TNM stage was correctly identified in 67% of [18F]FLT scans, compared to 85% of [18F]FDG scans

Yap et al. 2006 [24]

22

[18F]FLT SUVmax: 1.6 [18F]FDG SUVmax: 3.1

[18F]FLT: ADC (n = 9): 1.11

SqCC (n = 3): 1.7

LCC (n = 1): 3.6

[18F]FDG: ADC (n = 9): 1.87

SqCC (n = 3): 3.53

LCC (n = 1) = 7

Diagnosis Staging

0 (n = 3);

IA (n = 5); IB (n = 2);

IIA (n = 1);

IIIA (n = 2); IIIB (n = 2);

IV (n = 7)

Histopathology

Ki-67

[18F]FDG

[18F]FDG uptake was significantly higher than [18F]FLT uptake (p < 0.05)

[18F]FLT overstaged (9%) of patients and understaged (36%) of patients whereas [18F]FDG overstaged (27%) of patients and understaged (14%) of patients

Yamamoto et al. 2007 [25]

18

[18F]FLT SUVmean: 3.6 [18F]FDG SUVmean: 8.5

[18F]FLT: ADC (n = 7): 3.43

SqCC (n = 5): 6.26

[18F]FDG: ADC (n = 7): 7.46

SqCC (n = 5) = 16.02

Diagnosis

T1N0M0 (n = 8); T1N2M0 (n = 1); T2N0M0 (n = 4); T2N1M0 (n = 2); T2N2M0 (n = 1); T3N2M0 (n = 1); T4N0M0 (n = 1)

Histopathology

Ki-67

[18F]FDG

[18F]FDG uptake was significantly higher than [18F]FLT uptake (p < 0.0003)

Tian et al. 2008 [21]

55

[18F]FLT SUVmean: 3.54 [18F]FDG SUVmean: 8.13

[18F]FLT: ADC (n = 10): 3.72

SqCC (n = 2): 4.4

[18F]FDG: ADC (n = 10): 7.76

SqCC (n = 2): 9

Diagnosis with dual tracers [18F]FDG/[18F]FLT

NA

Histopathology

[18F]FDG

RECIST

The sensitivity and specificity of [18F]FDG and [18F]FLT were 87.5% and 58.97% and 68.75% and 76.92%, respectively. Improved sensitivity and specificity, 100% and 89.74%, respectively were shown with dual tracer [18F]FDG/[18F]FLT

Yamamoto et al. 2008 [19]

34

[18F]FLT SUVmean: 3.5 [18F]FDG SUVmean: 11.4

[18F]FLT: ADC (n = 16): 4.28

SqCC (n = 16): 5.57

SCLC (n = 2): 2.35

[18F]FDG: ADC (n = 16): 9.88

SqCC (n = 16): 12.72

SCLC (n = 2): 10.7

Diagnosis Staging

T1N1M0 (n = 1); T1N2M0 (n = 1);

T2N0M0 (N = 10); T2N0M1 (N = 1); T2N1M1 (N = 2); T2N2M0 (N = 2);

T3N0M0 (n = 1); T3N1M0 (n = 1); T3N2M0 (n = 2);

T4N0M0 (n = 2)

Histopathology

[18F]FDG

[18F]FDG uptake was significantly higher than [18F]FLT uptake (P < 0.0001). [18F]FLT showed same sensitivity and higher specificity and accuracy than [18F]FDG

Yang et al. 2010 [20]

31

[18F]FLT SUVmax: 4.2 [18F]FDG SUVmax: 7.7

[18F]FLT: ADC (n = 13): 3.8

SqCC (n = 11) = 5.7

[18F]FDG: ADC (n = 13): 8.4

SqCC (n = 11) = 8.1

Diagnosis Staging

T1N0 (n = 4); T1N1 (n = 5); T1N2 (n = 2);

T2N0 (n = 6); T2N1 (n = 4); T2N2 (n = 2);

T3N0 (n = 3); T3N1 (n = 3); T3N2 (n = 2)

Histopathology

[18F]FDG

[18F]FLT showed significantly lower sensitivity (p = 0.031) for primary lesions. [18F]FLT showed better accuracy and specificity but lower sensitivity for nodal staging than [18F]FDG

Xu et al. 2016 [26]

14

[18F]FLT SUVmean: 4.96 [18F]FDG SUVmean: 8.12

[18F]FLT: ADC (n = 11): 5.14

SqCC (n = 3): 4.28

[18F]FDG: ADC (n = 11): 8.38

SqCC (n = 3): 7.13

Staging

T3N0M0 (n = 4); T3N1M0 (n = 3); T3N1M1 (n = 2);

T4N0M0 (n = 1); T4N0M1 (n = 1); T4N1Mx (n = 1); T4N1M0 (n = 1); T4N1M1 (n = 1)

Histopathology

[18F]FDG

[18F]FDG uptake was significantly higher than [18F]FLT uptake (p = 0.01). [18F]FLT showed better accuracy and specificity but lower sensitivity for nodal staging than [18F]FDG

Wang et al. 2016 [18]

55

[18F]FLT SUVmax: 2.9 [18F]FDG SUVmax: 6.8

NA

Diagnosis

NA

Histopathology

Ki-67

[18F]FDG

[18F]FDG uptake was significantly higher than [18F]FLT uptake (p < 0.001)

[18F]FLT showed lower sensitivity (68.75%) compared with 87.8% for [18F]FDG but higher specificity (77%) than [18F]FDG (59%)

[18F]FLT can distinguish cancer from other solitary pulmonary nodules

[18F]FDG showed an overlap in detecting cancer and tuberculosis

  1. All of the reports in this table were single centre studies except Tian et al. 2008 [21]
  2. n; Number of patients, NA; Not available, LC; Lung cancer, SCLC; Small cell lung cancer, NSCLC; non-small cell lung cancer, ADC; Adenocarcinoma, SqCC; Squamous cell carcinoma, LCC; Large cell lung carcinoma, TNM; Tumour, nodal involvement and metastases, PET; Positron emission tomography, [18F]FDG; [18F]fluorodeoxyglucose, [18F]FLT; 3'-deoxy-3'-[18F]fluorothymidine, SUV; Standardised uptake value, SUVmean; Mean standardised uptake value, SUVmax; Maximum standardised uptake value, SPF; S-phase fraction