***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: We investigated whether uptake of the thymidine analogue 3-deoxy-3-[(18)F]fluorothymidine ( [(18)F]FLT ) reflects proliferation in solitary pulmonary nodules ( SPNs ) . Thirty patients with SPNs were prospect ively examined with positron emission tomography .  St and ardized uptake values were calculated for quantification of FLT uptake . Histopathology revealed 22 malignant and 8 benign lesions .  Proliferation was evaluated by Ki-67 immunostaining and showed a mean proliferation fraction of 30.9 % ( range , 1 - 65 % ) in malignant SPNs and < 5 % in benign lesions . Linear regression analysis indicated a significant correlation between FLT-st and ardized uptake values and proliferative activity ( P < 0.0001 ; r = 0.87 ) . FLT uptake was specific for malignant lesions and may be used for differential diagnosis of SPNs , assessment of proliferation , and estimation of prognosis Purpose The purpose of this prospect i ve study was to clarify the individual and combined role of l-methyl-11C-methionine-positron emission tomography ( MET-PET ) and 3′-deoxy-3′-[18F]fluorothymidine (FLT)-PET in tumor detection , noninvasive grading , and assessment of the cellular proliferation rate in newly diagnosed histologically verified gliomas of different grade s. Material s and methods Forty-one patients with newly diagnosed gliomas were investigated with MET-PET before surgery . Eighteen patients were also examined with FLT-PET .  MET and FLT uptakes were assessed by st and ardized uptake value of the tumor showing the maximum uptake ( SUVmax ) , and the ratio to uptake in the normal brain parenchyma ( T/N ratio ) . All tumors were grade d by the WHO grading system using surgical specimens , and the proliferation activity of the tumors were determined by measuring the Ki-67 index obtained by immunohistochemical staining . Results On semiquantitative analysis , MET exhibited a slightly higher sensitivity ( 87.8 % ) in tumor detection than FLT ( 83.3 % ) , and both tracers were 100 % sensitive for malignant gliomas . Low- grade gliomas that were false negative on MET-PET also were false negative on FLT-PET . Although the difference of MET SUVmax and T/N ratio between grade s II and IV gliomas was statistically significant ( P < 0.001 ) , there was a significant overlap of MET uptake in the tumors . The difference of MET SUVmax and T/N ratio between grade s II and III gliomas was not statistically significant . Low- grade gliomas with oligodendroglial components had relatively high MET uptake . The difference of FLT SUVmax and T/N ratio between grade s III and IV gliomas was statistically significant ( P < 0.01 ) . Again , the difference of FLT SUVmax and T/N ratio between grade s II and III gliomas was not statistically significant . Grade III gliomas with non-contrast enhancement on MR images had very low FLT uptake . In 18 patients who underwent PET examination with both tracers , a significant but relatively weak correlation was observed between the individual SUVmax of MET and FLT ( r = 0.54 , P < 0.05 ) and T/N ratio of MET and FLT ( r = 0.56 , P < 0.05 ) . Total FLT uptake in the tumor had a higher correlation ( r = 0.89 , P < 0.001 ) with Ki-67 proliferation index than MET uptake ( r = 0.49 , P < 0.01 ) . Conclusions PET studies using MET and FLT are useful for tumor detection in newly diagnosed gliomas . However , there is no complimentary information in tumor detection with simultaneous measurements of MET- and FLT-PET in low grade gliomas . FLT-PET seems to be superior than MET-PET in noninvasive tumor grading and assessment of proliferation activity in gliomas of different grade We have determined the ability of positron emission tomography ( PET ) with the thymidine analogue 3'-deoxy-3'-[(18)F]fluorothymidine ( FLT ) to detect manifestation sites of malignant lymphoma , to assess proliferative activity , and to differentiate aggressive from indolent tumors . In this prospect i ve study , FLT-PET was done additionally to routine staging procedures in 34 patients with malignant lymphoma . Sixty minutes after i.v . injection of approximately 330 MBq FLT , emission and transmission scanning was done . Tracer uptake in lymphoma was evaluated semiquantitatively by calculation of st and ardized uptake values ( SUV ) and correlated to tumor grading and proliferation fraction as determined by Ki-67 immunohistochemistry . FLT-PET detected a total of 490 lesions compared with 420 lesions revealed by routine staging . In 11 patients with indolent lymphoma , mean FLT-SUV in biopsied lesions was 2.3 ( range , 1.2 - 4.5 ) . In 21 patients with aggressive lymphoma , a significantly higher FLT uptake was observed ( mean FLT-SUV , 5.9 ; range , 3.2 - 9.2 ; P < 0.0001 ) and a cutoff value of SUV = 3 accurately discriminated between indolent and aggressive lymphoma . Linear regression analysis indicated significant correlation of  FLT uptake in biopsied lesions and proliferation fraction ( r = 0.84 ; P < 0.0001 ) . In this clinical study , FLT-PET was suitable for imaging malignant lymphoma and noninvasive assessment of tumor grading . Due to specific imaging of proliferation , FLT may be a superior PET tracer for detection of malignant lymphoma in organs with high physiologic fluorodeoxyglucose uptake and early detection of progression to a more aggressive histology or potential transformation Abstract The aim of this study was to evaluate the feasibility of using [ 18F ] 3′-deoxy-3′-fluorothymidine ( FLT ) positron emission tomography ( PET ) for the diagnosis and grading of brain tumors . Methods The patient population comprised 26 patients ( 15 males , 11 females ) with brain tumors ( n=18 ) or nontumorous lesions ( n=8 ) .  2-[18F]fluoro-2-deoxy-d-glucose ( FDG ) and FLT PET images were obtained using a dedicated PET scanner 1 h after the injection of 370 MBq of FDG or FLT . Uptake of FDG and FLT by the lesions was visually and semiquantitatively assessed in comparison with normal brain tissue . Results Of 26 brain lesions , four showed increased FDG uptake compared with normal gray matter ( grade 5 ) . These four lesions showed intensely increased FLT uptake and were all high- grade tumors . Twenty-two lesions with similar ( grade 4 ) or decreased ( grade s 1–3 ) FDG uptake compared with normal gray matter showed variable pathology . Among the 18 brain tumors , FLT PET showed increased uptake in all 12 high- grade tumors but FDG uptake was variable . In 22 brain lesions with similar or decreased uptake compared with normal gray matter on FDG PET , the sensitivity and specificity of FLT PET  for the diagnosis of brain tumor were 79 % ( 11/14 ) and 63 % ( 5/8 ) , respectively . The uptake ratios of 14 brain tumors on FLT PET were significantly higher than the lesion to gray matter ratios ( p=0.012 ) and lesion to white matter ratios ( p=0.036 ) of FDG uptake and differed significantly between high ( 5.1±2.6 ) and low ( 2.1±1.1 ) grade tumors ( p=0.029 ) . In nine gliomas , FLT uptake was significantly correlated with the Ki-67 proliferation index ( rho=0.817 , p=0.007 ) . Conclusion These findings indicate that FLT PET is useful for evaluating tumor grade and cellular proliferation in brain tumors . It displayed high sensitivity and good contrast in evaluating brain lesions that showed similar or decreased uptake compared with normal gray matter on FDG PET . FLT PET , however , did not appear to be sufficiently useful for differentiating tumors from nontumorous lesions The prognostic significance of tumour cell proliferation was investigated in a series of 418 gastric carcinomas using the monoclonal antibody MIB-1 .  Owing to strong intratumoural heterogeneity of MIB-1 expression three different proliferation indices ( PIs ) were determined in all carcinomas : ( 1 ) PImax in areas of maximal tumour cell proliferation , ( 2 ) PIr and in areas r and omly distributed over the whole tumour . ( 3 ) PIfront in areas exclusively located at the tumour invasion front . There was a strong intertumoral heterogeneity with PImax ranging from 4.9 % to 92.2 % , PIr and ranging from 3.4 % to 81.4 % and PIfront ranging from 4.2 % to 87.1 % . The mean values were 51.3 % + /- 19.7 for PImax , 34.2 % + /- 18.3 for PIr and and 37.2 % + /- 19.5 for PIfront . Whereas no statistically significant correlation could be found between proliferative activity and the clinicopathological parameters depth of invasion , lymph node involvement or grade of tumour differentiation , there was a positive correlation between a high proliferation index at the tumour invasion front ( PIfront ) and the presence of blood or lymphatic vessel invasion . No significant correlation could be demonstrated between the different proliferation indices and survival , even when different subgroups of patients were analysed separately . The present results suggest that the immunohistochemical evaluation of the proliferation activity has no predictive value for the prognosis of gastric cancer patients or the identification of subgroups of patients who may be at higher risk Background and aims : Positron emission tomography ( PET ) using 18F labelled 2-fluoro-2-deoxy-D-glucose ( 18FDG ) is an established imaging tool , although the recent development of a biologically stable thymidine analogue [ 18F ] 3′-deoxy-3-fluorothymidine ( 18FLT ) has allowed PET to image cellular proliferation by utilising the salvage pathway of DNA synthesis . In this study , we have compared uptake of 18FLT and 18FDG with MIB-1 immunohistochemistry to evaluate the role of PET in quantifying in vivo cellular proliferation in colorectal cancer ( CRC ) . Patients and methods : Patients with resectable , primary , or recurrent CRC were prospect ively studied . Thirteen lesions from 10 patients ( five males , five females ) , median age 68 years ( range 54–87 ) , were evaluated . Patients underwent 18FDG and 18FLT PET scanning .  Tracer uptake within lesions was quantified using st and ardised uptake values ( SUVs ) . Histopathological examination and MIB-1 immunohistochemistry were performed on all lesions , and proliferation quantified by calculating a labelling index ( % of MIB-1 positively stained nuclei within 1500 tumour cells ) . Results : Histology confirmed adenocarcinoma in 12 of 13 lesions ; the remaining lesion was reactive . All eight extrahepatic lesions were visualised using both 18FLT and 18FDG . Three of the five resected liver metastases were also avid for 18FLT and showed high proliferation , while the remaining two lesions which demonstrated no uptake of 18FLT had correspondingly very low proliferation . There was a statistically significant positive correlation ( r = 0.8 , p<0.01 ) between SUVs of the tumours visualised with 18FLT and the corresponding MIB-1 labelling indices . No such correlation was demonstrated with 18FDG avid lesions ( r = 0.4 ) . Conclusions : 18FLT PET correlates with cellular proliferation markers in both primary and metastatic CRC . This technique could provide a mechanism for in vivo grading of malignancy and early prediction of response to adjuvant chemotherapy Diagnosis is a critical component of health care , and clinicians , policymakers , and patients routinely face a range of questions regarding diagnostic tests . They want to know whether testing improves outcome ; what test to use , purchase , or recommend in practice guidelines ; and how to interpret test results . Well- design ed  diagnostic test accuracy studies can help in making these decisions , provided that they transparently and fully report their participants , tests , methods , and results as facilitated , for example , by the STARD ( St and ards for Reporting of Diagnostic Accuracy ) statement ( 1 ) . That 25-item checklist was published in many journals and is now adopted by more than 200 scientific journals worldwide . As in other areas of science , systematic review s and meta- analysis of accuracy studies can be used to obtain more precise estimates when small studies addressing the same test and patients in the same setting are available . Review s can also be useful to establish whether and how scientific 
    Output:
    
The meta- analysis showed that given an appropriate study design the FLT/Ki-67 correlation is significant and independent of cancer type .
In terms of the cancer type subgroup analysis there is sufficient data to support a strong FLT/Ki-67 correlation for brain , lung and breast cancer .
INTERPRETATION This systematic review and meta- analysis highlights the importance of the methods used in validation studies comparing FLT-PET imaging with the biomarker Ki-67 .
The correlation is significant and independent of cancer type provided a study design that uses Ki-67 average measurements , regardless of nature of sample , or whole surgical sample s when measuring Ki-67 maximum expression .
Sufficient data to support a strong correlation for brain , lung and breast cancer exist .