This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Buck, A. K. Articles by Neumaier, B. Search for Related Content PubMed PubMed Citation Articles by Buck, A. K. Articles by Neumaier, B.

3-Deoxy-3-[¹⁸F]Fluorothymidine-Positron Emission Tomography for Noninvasive Assessment of Proliferation in Pulmonary Nodules

Departments of Nuclear Medicine [A. K. B., H. S., M. v. d. H., G. G., S. N. R., B. N.], Internal Medicine II [M. H.], Thoracic Surgery [G. H., F. L.], and Pathology [T. M.], Universit of Ulm, D-89081 Ulm, Germany

	ABSTRACT

Top ABSTRACT Introduction Materials and Methods Results Discussion REFERENCES

 
We investigated whether uptake of the thymidine analogue 3-deoxy-3-[¹⁸F]fluorothymidine ([¹⁸F]FLT) reflects proliferation in solitary pulmonary nodules (SPNs). Thirty patients with SPNs were prospectively examined with positron emission tomography. Standardized 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-standardized 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.

	Introduction

Top ABSTRACT Introduction Materials and Methods Results Discussion REFERENCES

 
Evaluation of SPNs² remains one of the most common diagnostic problems in daily clinical practice (1) . Only half of the resected lesions are related to malignant disease (1) , and many of the nonmalignant lesions represent inflammatory processes (2) . PET using the glucose analogue FDG enables noninvasive differentiation between benign and malignant lesions because glucose consumption is elevated in malignant tumors (3) . FDG uptake, however, is not specific for malignancies because false positive findings were also reported in inflammation, muscle activity, or sarcoidosis (2) . A study in patients with elevated FDG uptake in pancreatic tumors indicated that determination of the proliferation rate clearly differentiated cancer from inflammation (4) . Recently, Shields et al. (5) developed the new PET tracer FLT for noninvasive measurement of tumor proliferation. This thymidine analogue was reported to accumulate in proliferating cells after intracellular trapping because of phosphorylation by thymidine kinase 1 (6) . This first study in humans was conducted to evaluate the correlation between [¹⁸F]FLT uptake and the proliferation rate in SPNs.

	Materials and Methods

Top ABSTRACT Introduction Materials and Methods Results Discussion REFERENCES

 
Patients.
This prospective study consisted of 30 patients (20 men and 10 women) with a mean age of 61.9 ± 6.8 years (range, 37–88 years). Patients were included when pulmonary nodules on CT with and without contrast enhancement were suspicious for a malignant tumor. None of the patients had prior surgery, chemotherapy, or radiation therapy. Nineteen patients had resective surgery up to 10 days after FLT-PET. Core biopsy specimens were used to evaluate the proliferation in the other 11 patients. All patients gave written consent to participate in this study, which was approved by the local ethical committee.

Histopathology.
Histopathological examination of the resected specimens revealed 22 malignant tumors [16 NSCLC, 1 small cell lung cancer, 1 non-Hodgkin’s lymphoma, and pulmonary metastases in 4 patients (1 colorectal cancer, 2 renal cell carcinoma, and 1 osteosarcoma)] and 8 benign tumors (1 bronchopulmonary chondroma, 3 bronchiolitis, 1 tuberculoma, 1 focal fibrosis, and 2 undefined tumors; malignancy excluded by clinical course).

Immunostaining.
A standard peroxidase-conjugated streptavidin-biotin complex method was used (DAKO Diagnostika, Hamburg, Germany), and 3,3'-diaminobenzidine (Sigma-Aldrich, Deisenhofen, Germany) served as chromogen (4) . Briefly, formalin-fixed, paraffin-embedded sections (5 µm) of resected specimens were dewaxed, rehydrated, and then microwaved in 0.01 M citrate buffer for 30 min. For immunostaining, MIB-1 antibody (Dianova, Hamburg, Germany), a monoclonal murine antibody specific for human nuclear antigen Ki-67, was used as the primary antibody in a 1:500 dilution. Sections were lightly counterstained with hematoxylin. The primary antibody was omitted on sections used as negative controls. Sections obtained from highly proliferating lymph node tissue of a reference patient who was not included in our series served as a positive control for proliferating cells. An evaluation of MIB-1 immunostaining was carried out in an area with high cellularity. All epithelial cells with nuclear staining of any intensity were defined as positive. Proliferative activity was described as the percentage of MIB-1-stained nuclei.

Morphometry.
Histopathological slides were scored by a pathologist experienced in this field who was blinded to the patients’ clinical data. The fraction of stained nucleus profile per total number of nucleus profiles was estimated by counting 600 nuclei/slide and three slides/case. For this purpose, the computer assisted imaging system Optimas 6.2 (Media Cybernetics, Inc., Silver Spring, MD) was used. Slides were analyzed by light microscopy, and three representative images of each slide were transferred to the computer frame by a video camera.

[¹⁸F]FLT Synthesis.
[¹⁸F]FLT was produced via benzoyl-protected anhydrothymidine according to the method reported by Machulla (7) . Radiosynthesis was carried out remotely and automatically in a PET tracer synthesizer from Nuclear Interface (Münster, Germany). [¹⁸F]Fluoride was produced via the ¹⁸O(p,n) ¹⁸F nuclear reaction by bombardment of isotopically enriched [¹⁸O]water with an 18 MeV proton beam at the Cyclone 18/9 cyclotron (IBA, Louvaine-la-Neuve, Belgium). After recovery of [¹⁸O]water using a QMA cartridge (Waters, Milford, MA), [¹⁸F]fluoride was eluted with 360 µl of K₂CO₃ solution (3.3 mg K₂CO₃). Twenty mg of Kryptofix 2.2.2 (Merck, Darmstadt, Germany) in 0.7 ml of acetonitrile was added, and the cryptate of [¹⁸F]fluoride and potassium carbonate was evaporated to dryness. The evaporation step was repeated with 1 ml of acetonitrile to remove any traces of moisture. Then a solution of 10 mg of 5'-benzoyl-3',2-anhydrothymidine in 1 ml of DMSO was added to the dry cryptate, and the resulting solution kept at 160°C for 10 min. Removal of the benzoyl-protecting group was achieved by hydrolysis with 1% 350-µl 1 M NaOH and heating it to 55°C for 10 min. The hydrolysate was transferred through an Alumina N (Waters) to retard unreacted [¹⁸F]fluoride. Subsequently, [¹⁸F]FLT was purified using preparative high-performance liquid chromatography. For the separation of [¹⁸F]FLT, a C-18 column (Phenomenex; Luna 5 µ, 250 x 10 mm) was used and eluted with isotonic sodium chloride solution and ethanol (90/10, v/v) at a flow rate of 5 ml/min. Retention time of [¹⁸F]FLT was 10 min. It was separated from other ¹⁸F impurities, mainly [¹⁸F]fluoride. Finally the collected product was sterile filtered through a 0.2 µm Sterifix filter (Braun, Melsungen, Germany).

FLT-PET Imaging.
PET was performed using a high-resolution full ring scanner (ECAT Exact; Siemens/CTI, Knoxville, TN), which produces 47 contiguous slices/bed position. Axial field of view is 15.5 cm/bed position. Patients fasted for at least 6 h before undergoing PET. Static emission scans were started 45 min after injection of 265–370 MBq of [¹⁸F]FLT (mean, 334 MBq). The acquisition time was 10 min/bed position for emission scanning. Eight-min transmission scans with a germanium-68/gallium-68 ring source were obtained for attenuation correction. Five bed positions covered a field of view of 77.5 cm in each patient. Images were reconstructed using an iterative reconstruction algorithm (8) . For SUV calculation, circular regions of interest were drawn around the area with focally increased pulmonary FLT uptake.

Data Analysis.
Data are presented as mean, median, range, and SD. Amounts of Ki-67 positive cells and FLT-SUVs were compared using linear regression analysis. Differences were considered statistically significant when P < 0.05.

	Results

Top ABSTRACT Introduction Materials and Methods Results Discussion REFERENCES

 
FLT-PET.
Mean [¹⁸F]FLT uptake (FLT-SUV) in SPN was 2.8 (median, 3.1; range, 0–6.4; and SD, 1.8), and the mean maximum FLT-SUV was 4.2 (median, 4.4; range, 0–10.4; and SD, 2.9; Table 1 ). NSCLC was the predominant tumor entity. With the exception of one carcinoma in situ (patient 16) and a highly differentiated large cell NSCLC (patient 6) with a low proliferation index of 10%, FLT-SUV was markedly increased in NSCLC (Fig. 1) . On the basis of the expert qualitative review, sensitivity of FLT-PET is 86%. Using a cutoff level of SUV_max = 1.5, sensitivity of FLT-PET is 77%. Mean FLT-SUV was 3.5 (median, 3.2; range, 0–6.4; and SD, 1.7) in NSCLC, and the mean maximum FLT-SUV was 5.2 (median, 4.7; range, 0–10.4; and SD, 2.6). All benign tumors presented without [¹⁸F]FLT uptake. Hence, SUVs were not calculated in these lesions.

View larger version (131K): [in this window] [in a new window]   Fig. 1. A, FLT-PET of patient 15 with NSCLC with high proliferation fraction and increased FLT uptake (SUV, 6.38) in the tumor margin (70% stained nuclei in the tumor margin, right). Middle, transverse sections of PET and spiral CT. B, patient 12 with a low proliferating NSCLC (25% stained nuclei, right). FLT-PET (left) shows moderate FLT-uptake (SUV, 1.11). Middle, corresponding transverse sections of the spiral CT.

Ki-67 Immunohistochemistry.
All malignant tissue specimens contained Ki-67 positive cells. Stained nuclei mainly belonged to epithelial cells, and a very small portion to inflammatory cells. Ki-67 positivity ranged from 1 to 70% of sampled epithelial nucleus profiles (Table 1) . The mean proliferation fraction in malignant SPNs was 30.9% (median, 33.5%; range, 1–70%; and SD, 18.9%), and in NSCLC, it was 33% (median, 35%; range, 10–70%; and SD, 6.5%).

More than 40% of stained nuclei was present in 8 malignant lesions. The mean proliferation fraction was 15% (range, 0–35%) in lung metastases. Only 1 benign nodule contained Ki-67 positive cells (patient 25 with solitary tuberculoma, Ki-67 index, 5%). In control sections in which the primary antibody was omitted, no positive nuclear staining was present.

Correlation between Proliferative Activity and FLT Uptake.
Immunoreactivity to Ki-67 antigen was present in all malignant nodules. Linear regression analysis indicated a highly significant correlation between FLT-SUV and Ki-67 index in the malignant lesions (P < 0.0001; r = 0.87; Fig. 2 ). In benign tumors, maximum proliferation rate was <5% and no FLT uptake was visible.

View larger version (15K): [in this window] [in a new window]   Fig. 2. Linear regression analysis demonstrates a significant correlation between proliferative fraction and FLT uptake in SPN. , NSCLC; , patient 16 with a carcinoma in situ (NSCLC) negative on FLT-PET; , other malignant lesions.

	Discussion

Top ABSTRACT Introduction Materials and Methods Results Discussion REFERENCES

Despite the perfect specificity of 100%, FLT-PET showed a lack of sensitivity in a highly differentiated lung tumor and in metastases from colorectal cancer. That means, in effect, that histopathological examination for evaluation cannot be omitted when SPNs do not accumulate [¹⁸F]FLT. It has to be mentioned that our series consisted exclusively of untreated patients with suspicious lung lesions. The 100% rate of specificity and the 86% rate of sensitivity may be different for the evaluation of patients who have undergone treatment.

The proliferation rate is currently discussed as a prognostic marker (9 , 10) . For example, patients with increased tumor proliferation as determined by the thymidine labeling index or Ki-67 immunostaining showed decreased survival in NSCLC (11 , 12) . However, in another series, Ki-67 staining in stage I NSCLC was not a significant predictor of outcome (13) . Commonly, proliferation cannot be measured in the entire tumor but only in a small, probably representative portion. Because of sampling errors, this method is naturally not precise. Therefore, noninvasive determination of the proliferation of the entire tumor should be helpful for a more exact estimation of the prognosis with FLT-PET.

Recently, a significant correlation between FDG uptake and proliferation in NSCLC was suggested (14 , 15) . However, the correlation coefficient of r = 0.74 indicated that tumoral FDG uptake originated from additional mechanisms such as expression of glucose transporters (16) rather than from proliferation alone. Several authors reported that high FDG uptake in NSCLC was associated with decreased survival (17, 18, 19) . Correlation to proliferative activity has not been assessed in these studies. Compared with FDG-PET studies, the number of patients is relatively small in our series. The correlation coefficient and the perfect specificity may not hold up in a larger series. However, the greater correlation coefficient of 0.9 suggested that FLT reflects proliferation better than FDG. The high tracer uptake observed in the bone marrow supports the concept of a preferential tracer accumulation in proliferating cells (Fig. 1) .

In summary, [¹⁸F]FLT may be used for noninvasive assessment of proliferation in SPN, which was a typical feature of malignant lesions. Furthermore, a better prediction of prognosis and improved selection of the appropriate therapeutic regimen seems feasible.

	FOOTNOTES

 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom requests for reprints should be addressed, at Universit of Ulm, Robert-Koch-Strasse 8, D-89081 Ulm, Germany. Phone: 0731-500-24504; Fax: 0731-500-24503; E-mail: andreas.buck{at}medizin.uni-ulm.de

² The abbreviations used are: SPN, solitary pulmonary nodule; PET, positron emission tomography; FDG, 2-[¹⁸F]fluoro-2-deoxy-D-glucose; FLT, 3-deoxy-3'-fluorothymidine; NSCLC, non-small cell lung cancer; SUV, standardized uptake value; CT, computed tomography.

Received 2/15/02. Accepted 5/ 1/02.

	REFERENCES

Top ABSTRACT Introduction Materials and Methods Results Discussion REFERENCES

 

1. Svensen S., Viggiano R., Midthun D., Müller N., Sherrick A., Ymashita K., Naidich D., Patz E., Hartman T., Muhm J., Weaver A. Lung nodule enhancement at CT: multicenter study. Radiology, 214: 73-80, 2000.[Abstract/Free Full Text]
2. Shreve P., Anzai Y., Wahl R. Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants. Radiographics, 19: 61-77, 1999.[Abstract/Free Full Text]
3. Kalff V., Hicks R. J., MacManus M. P., Binns D. S., McKenzie A. F., Ware R. E., Hogg A., Ball D. L. Clinical impact of (18)F fluorodeoxyglucose positron emission tomography in patients with non-small cell lung cancer: a prospective study. J. Clin. Oncol., 19: 111-118, 2001.[Abstract/Free Full Text]
4. Buck A. C., Schirrmeister H. H., Guhlmann C. A., Diederichs C. G., Shen C., Buchmann I., Kotzerke J., Birk D., Mattfeldt T., Reske S. N. Ki-67 immunostaining in pancreatic cancer and chronic active pancreatitis: does in vivo FDG uptake correlate with proliferative activity?. J. Nucl. Med., 42: 721-725, 2001.[Abstract/Free Full Text]
5. Shields A. F., Grierson J. R., Dohmen B. M., Machulla H. J., Stayanoff J. C., Lawhorn-Crews J. M., Obradovich J. E., Muzik O., Mangner T. J. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat. Med., 4: 1334-1336, 1998.[Medline]
6. Sherley J. L., Kelly T. J. Regulation of human thymidine kinase during the cell cycle. J. Biol. Chem., 263: 8350-8358, 1988.[Abstract/Free Full Text]
7. Machulla H. J., Blocher A., Kuntzsch M., Grierson J. R. Simplified labeling approach for synthesizing 3'-deoxy-3'-[¹⁸F]fluorothymidine ([¹⁸F]FLT). J. Radioanal. Nucl. Chem., 24: 843-846, 2000.
8. Schmidlin P. Improved iterative reconstruction using variable projection binning and abbreviated convolution. Eur. J. Nucl. Med., 21: 930-936, 1994.[Medline]
9. Hommura F., Dosaka-Akita H., Mishina T., Nishi M., Kojima T., Hiroumi H., Ogura S., Shimizu M., Katoh H., Kawakami Y. Prognostic significance of p27^KIP1 protein and ki-67 growth fraction in non-small cell lung cancers. Clin. Cancer Res., 6: 4073-4081, 2000.[Abstract/Free Full Text]
10. Dosaka-Akita H., Hommura F., Mishina T., Ogura S., Shimizu M., Katoh H., Kawakami Y. A risk-stratification model of non-small cell lung cancers using cyclin E, ki-67, and ras p21: different roles of G1 cyclins in cell proliferation and prognosis. Cancer Res., 61: 2500-2504, 2001.[Abstract/Free Full Text]
11. Harpole D. H. Prognostic issues in non-small cell lung cancer. Chest, 107: 267-269, 1995.
12. Apolinario R. M., van der Valk P., de Jong J. S., Deville W., van Ark-Otte J., Dingemans A. M., van Mourik J. C., Postmus P. E., Pinedo H. M., Giaccone G. Prognostic value of the expression of p53, bcl-2, and bax oncoproteins, and neovascularization in patients with radically resected non-small cell lung cancer. J. Clin. Oncol., 15: 2456-2466, 1997.[Abstract/Free Full Text]
13. D’Amico T. A., Aloia T. A., Moore M. B., Herndon J. E., Brooks K. R., Lau C. L., Harpole D. H. Molecular biologic substaging of stage I lung cancer according to gender and histology. Ann. Thorac. Surg., 69: 882-886, 2000.[Abstract/Free Full Text]
14. Higashi K., Ueda Y., Yagishita M., Arisaka Y., Sakurai A., Oguchi M., Seki H., Nambu Y., Tonami H., Yamamoto I. FDG PET measurement of the proliferative potential of non-small cell lung cancer. J. Nucl. Med., 41: 85-92, 2000.[Abstract/Free Full Text]
15. Vesselle H., Schmidt R. A., Pugsley J. M., Li M., Kohlmyer S. G., Vallires E., Wood D. E. Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography. Clin. Cancer Res., 6: 3837-3844, 2000.[Abstract/Free Full Text]
16. Brown R. S., Leung J. Y., Kison P. V., Zasadny K. R., Flint A., Wahl R. L. Glucose transporters and FDG uptake in untreated primary human non-small cell lung cancer. J. Nucl. Med., 40: 556-565, 1999.[Abstract/Free Full Text]
17. Vansteenkiste J. F., Stroobants S. G., Dupont P. J., De Leyn P. R., Verbeken E. K., Deneffe G. J., Mortelmans L. A., Demedts M. G. Prognostic importance of the standardized uptake value on (18)F-fluoro-2-deoxy-glucose-positron emission tomography scan in non-small cell lung cancer: an analysis of 125 cases. Leuven Lung Cancer Group. J. Clin. Oncol., 17: 3201-3206, 1999.[Abstract/Free Full Text]
18. Hicks R. J., Kalff V., MacManus M. P., Ware R. E., McKenzie A. F., Matthews J. P., Ball D. L. 18F-FDG PET provides high impact and powerful prognostic stratification in staging newly diagnosed non-small cell lung cancer. J. Nucl. Med., 42: 1596-1604, 2001.[Abstract/Free Full Text]
19. Mac Manus M. P., Hicks R. J., Ball D. L., Kalff V., Matthews J. P., Salminen E., Khaw P., Wirth A., Rischin D., McKenzie A. F-18 fluorodeoxyglucose positron emission tomography staging in radical radiotherapy candidates with non-small cell lung carcinoma: powerful correlation with survival and high impact on treatment. Cancer (Phila.), 92: 886-895, 2001.[Medline]

This article has been cited by other articles:

				J. R. Bading and A. F. Shields Imaging of Cell Proliferation: Status and Prospects J. Nucl. Med., June 1, 2008; 49(Suppl_2): 64S - 80S. [Abstract] [Full Text] [PDF]

				R. Ullrich, H. Backes, H. Li, L. Kracht, H. Miletic, K. Kesper, B. Neumaier, W.-D. Heiss, K. Wienhard, and A. H. Jacobs Glioma Proliferation as Assessed by 3'-Fluoro-3'-Deoxy-L-Thymidine Positron Emission Tomography in Patients with Newly Diagnosed High-Grade Glioma Clin. Cancer Res., April 1, 2008; 14(7): 2049 - 2055. [Abstract] [Full Text] [PDF]

				O. S. Tehrani, O. Muzik, L. K. Heilbrun, K. A. Douglas, J. M. Lawhorn-Crews, H. Sun, T. J. Mangner, and A. F. Shields Tumor Imaging Using 1-(2'-deoxy-2'-18F- Fluoro-{beta}-D-Arabinofuranosyl)Thymine and PET J. Nucl. Med., September 1, 2007; 48(9): 1436 - 1441. [Abstract] [Full Text] [PDF]

				H.-J. Wester Nuclear Imaging Probes: from Bench to Bedside Clin. Cancer Res., June 15, 2007; 13(12): 3470 - 3481. [Abstract] [Full Text] [PDF]

				E. G.C. Troost, W. V. Vogel, M. A.W. Merkx, P. J. Slootweg, H. A.M. Marres, W. J.M. Peeters, J. Bussink, A. J. van der Kogel, W. J.G. Oyen, and J. H.A.M. Kaanders 18F-FLT PET Does Not Discriminate Between Reactive and Metastatic Lymph Nodes in Primary Head and Neck Cancer Patients J. Nucl. Med., May 1, 2007; 48(5): 726 - 735. [Abstract] [Full Text] [PDF]

				A. K. Buck, M. Bommer, S. Stilgenbauer, M. Juweid, G. Glatting, H. Schirrmeister, T. Mattfeldt, D. Tepsic, D. Bunjes, F. M. Mottaghy, et al. Molecular Imaging of Proliferation in Malignant Lymphoma. Cancer Res., November 15, 2006; 66(22): 11055 - 11061. [Abstract] [Full Text] [PDF]

				J. Leyton, M. Lockley, J. L. Aerts, S. K. Baird, E. O. Aboagye, N. R. Lemoine, and I. A. McNeish Quantifying the Activity of Adenoviral E1A CR2 Deletion Mutants Using Renilla Luciferase Bioluminescence and 3'-Deoxy-3'-[18F]Fluorothymidine Positron Emission Tomography Imaging. Cancer Res., September 15, 2006; 66(18): 9178 - 9185. [Abstract] [Full Text] [PDF]

				J. Leyton, J. P. Alao, M. Da Costa, A. V. Stavropoulou, J. R. Latigo, M. Perumal, R. Pillai, Q. He, P. Atadja, E. W.-F. Lam, et al. In vivo Biological Activity of the Histone Deacetylase Inhibitor LAQ824 Is detectable with 3'-Deoxy-3'-[18F]Fluorothymidine Positron Emission Tomography. Cancer Res., August 1, 2006; 66(15): 7621 - 7629. [Abstract] [Full Text] [PDF]

				W. A. Weber Positron Emission Tomography As an Imaging Biomarker J. Clin. Oncol., July 10, 2006; 24(20): 3282 - 3292. [Abstract] [Full Text] [PDF]

				C. S. Yap, J. Czernin, M. C. Fishbein, R. B. Cameron, C. Schiepers, M. E. Phelps, and W. A. Weber Evaluation of Thoracic Tumors With 18F-Fluorothymidine and 18F- Fluorodeoxyglucose-Positron Emission Tomography. Chest, February 1, 2006; 129(2): 393 - 401. [Abstract] [Full Text] [PDF]

				A. H. Jacobs, A. Thomas, L. W. Kracht, H. Li, C. Dittmar, G. Garlip, N. Galldiks, J. C. Klein, J. Sobesky, R. Hilker, et al. 18F-Fluoro-L-Thymidine and 11C-Methylmethionine as Markers of Increased Transport and Proliferation in Brain Tumors J. Nucl. Med., December 1, 2005; 46(12): 1948 - 1958. [Abstract] [Full Text] [PDF]

				J. R. Tseng, M. Dandekar, M. Subbarayan, Z. Cheng, J. M. Park, S. Louie, and S. S. Gambhir Reproducibility of 3'-Deoxy-3'-18F-Fluorothymidine MicroPET Studies in Tumor Xenografts in Mice J. Nucl. Med., November 1, 2005; 46(11): 1851 - 1857. [Abstract] [Full Text] [PDF]

				L. M. Kenny, D. M. Vigushin, A. Al-Nahhas, S. Osman, S. K. Luthra, S. Shousha, R. C. Coombes, and E. O. Aboagye Quantification of Cellular Proliferation in Tumor and Normal Tissues of Patients with Breast Cancer by [18F]Fluorothymidine-Positron Emission Tomography Imaging: Evaluation of Analytical Methods Cancer Res., November 1, 2005; 65(21): 10104 - 10112. [Abstract] [Full Text] [PDF]

				M. R. Acker and S. C. Burrell Utility of 18F-FDG PET in Evaluating Cancers of Lung J. Nucl. Med. Technol., June 1, 2005; 33(2): 69 - 74. [Abstract] [Full Text] [PDF]

				W. Chen, T. Cloughesy, N. Kamdar, N. Satyamurthy, M. Bergsneider, L. Liau, P. Mischel, J. Czernin, M. E. Phelps, and D. H.S. Silverman Imaging Proliferation in Brain Tumors with 18F-FLT PET: Comparison with 18F-FDG J. Nucl. Med., June 1, 2005; 46(6): 945 - 952. [Abstract] [Full Text] [PDF]

				J. Leyton, J. R. Latigo, M. Perumal, H. Dhaliwal, Q. He, and E. O. Aboagye Early Detection of Tumor Response to Chemotherapy by 3'-Deoxy-3'-[18F]Fluorothymidine Positron Emission Tomography: The Effect of Cisplatin on a Fibrosarcoma Tumor Model In vivo Cancer Res., May 15, 2005; 65(10): 4202 - 4210. [Abstract] [Full Text] [PDF]

				L. K. Shankar and D. C. Sullivan Functional Imaging in Lung Cancer J. Clin. Oncol., May 10, 2005; 23(14): 3203 - 3211. [Abstract] [Full Text] [PDF]

				F. C. Detterbeck, J. F. Vansteenkiste, D. E. Morris, C. A. Dooms, A. H. Khandani, and M. A. Socinski Seeking a Home for a PET, Part 3: Emerging Applications of Positron Emission Tomography Imaging in the Management of Patients With Lung Cancer Chest, November 1, 2004; 126(5): 1656 - 1666. [Abstract] [Full Text] [PDF]

				H. Schirrmeister, M. Hetzel, J. Hetzel, T. Habig, C. Schumann, M. Bommer, P. Blum, H. von Beauvais, and A. Babiak Challenging Manifestations of Malignancies: CASE 3. Fibrinous Tracheitis: An Uncommon Manifestation of Hodgkin's Lymphoma J. Clin. Oncol., September 1, 2004; 22(17): 3642 - 3643. [Full Text] [PDF]

				A. van Waarde, D. C.P. Cobben, A. J.H. Suurmeijer, B. Maas, W. Vaalburg, E. F.J. de Vries, P. L. Jager, H. J. Hoekstra, and P. H. Elsinga Selectivity of 18F-FLT and 18F-FDG for Differentiating Tumor from Inflammation in a Rodent Model J. Nucl. Med., April 1, 2004; 45(4): 695 - 700. [Abstract] [Full Text] [PDF]

				G. Halter, A. K. Buck, H. Schirrmeister, I. Wurziger, F. Liewald, G. Glatting, B. Neumaier, L. Sunder-Plassmann, S. N. Reske, and M. Hetzel [18F] 3-deoxy-3'-fluorothymidine positron emission tomography: Alternative or diagnostic adjunct to 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography in the workup of suspicious central focal lesions? J. Thorac. Cardiovasc. Surg., April 1, 2004; 127(4): 1093 - 1099. [Abstract] [Full Text] [PDF]

				N. Oyama, D. E. Ponde, C. Dence, J. Kim, Y.-C. Tai, and M. J. Welch Monitoring of Therapy in Androgen-Dependent Prostate Tumor Model by Measuring Tumor Proliferation J. Nucl. Med., March 1, 2004; 45(3): 519 - 525. [Abstract] [Full Text]

				D. C.P. Cobben, B. F.A.M. van der Laan, B. Maas, W. Vaalburg, A. J.H. Suurmeijer, H. J. Hoekstra, P. L. Jager, and P. H. Elsinga 18F-FLT PET for Visualization of Laryngeal Cancer: Comparison with 18F-FDG PET J. Nucl. Med., February 1, 2004; 45(2): 226 - 231. [Abstract] [Full Text] [PDF]

				H. Barthel, E. Aboagye, and P. Price Reply Cancer Res., December 1, 2003; 63(23): 8560 - 8560. [Full Text] [PDF]

				D. C.P. Cobben, P. H. Elsinga, A. van Waarde, and P. L. Jager Correspondence re: H. Barthel et al., 3'-Deoxy-3'-[18F]fluorothymidine as a New Marker for Monitoring Tumor Response to Antiproliferative Therapy in Vivo with Positron Emission Tomography. Cancer Res., 63: 3791-3798, 2003. Cancer Res., December 1, 2003; 63(23): 8558 - 8559. [Full Text] [PDF]

				D L Francis, A Freeman, D Visvikis, D C Costa, S K Luthra, M Novelli, I Taylor, and P J Ell In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography Gut, November 1, 2003; 52(11): 1602 - 1606. [Abstract] [Full Text] [PDF]

				A. K. Buck, G. Halter, H. Schirrmeister, J. Kotzerke, I. Wurziger, G. Glatting, T. Mattfeldt, B. Neumaier, S. N. Reske, and M. Hetzel Imaging Proliferation in Lung Tumors with PET: 18F-FLT Versus 18F-FDG J. Nucl. Med., September 1, 2003; 44(9): 1426 - 1431. [Abstract] [Full Text] [PDF]

				H. Barthel, M. C. Cleij, D. R. Collingridge, O. C. Hutchinson, S. Osman, Q. He, S. K. Luthra, F. Brady, P. M. Price, and E. O. Aboagye 3'-Deoxy-3'-[18F]Fluorothymidine as a New Marker for Monitoring Tumor Response to Antiproliferative Therapy in Vivo with Positron Emission Tomography Cancer Res., July 1, 2003; 63(13): 3791 - 3798. [Abstract] [Full Text] [PDF]

				M. Wagner, U. Seitz, A. Buck, B. Neumaier, S. Schultheiss, M. Bangerter, M. Bommer, F. Leithauser, E. Wawra, G. Munzert, et al. 3'-[18F]Fluoro-3'-Deoxythymidine ([18F]-FLT) as Positron Emission Tomography Tracer for Imaging Proliferation in a Murine B-Cell Lymphoma Model and in the Human Disease Cancer Res., May 15, 2003; 63(10): 2681 - 2687. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Buck, A. K. Articles by Neumaier, B. Search for Related Content PubMed PubMed Citation Articles by Buck, A. K. Articles by Neumaier, B.