[11C]Choline as a PET biomarker for assessment of prostate cancer tumor models

Zheng, Qi; Gardner, Thomas A.; Raikwar, Sudhanshu P.; Kao, Chinghai; Stone, K. Lee; Martinez, Tanya D.; Mock, Bruce H.; Fei, Xiangshu; Wang, Ji Quan; Hutchins, Gary D.

doi:10.1016/j.bmc.2004.03.051

Cited by 61 publications

(38 citation statements)

References 28 publications

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“…Our biodistribution results are in accordance with the results of previous studies (15)(16)(17). At 10 min after injection, the target-to-background (aorta-to-blood) ratio was 5.5, indicating fast blood clearance.…”

Section: Discussionsupporting

confidence: 92%

Uptake of ¹¹C-Choline in Mouse Atherosclerotic Plaques

Laitinen¹,

Luoto²,

Någren³

et al. 2010

J Nucl Med

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The purpose of this study was to explore the feasibility of 11 C-choline in the assessment of the degree of inflammation in atherosclerotic plaques. Methods: Uptake of 11 C-choline was studied ex vivo in tissue samples and aortic sections excised from 6 atherosclerotic mice deficient for both low-density lipoprotein receptor and apolipoprotein B48 (LDLR 2/2 ApoB 100/100 ) and 5 control mice. The autoradiographs were compared with the immunohistology of the arterial sites. Results: The uptake of 11 C-choline (percentage of the injected activity per gram of tissue) in the atherosclerotic aortas of the LDLR 2/2 ApoB 100/100 mice was significantly higher (1.9-fold, P 5 0.0016) than that in the aortas of the control mice. The autoradiography analysis showed significantly higher uptake of 11 C-choline in the plaques than in healthy vessel wall (mean ratio, 2.3 6 0.6; P 5 0.014), prominently in inflamed plaques, compared with noninflamed plaque areas. Conclusion: We observed a high 11 C-choline uptake in the aortic plaques of atherosclerotic mice. Our data suggest that macrophages may be responsible for the uptake of 11 C-choline in the plaques.

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Section: Discussionsupporting

confidence: 92%

Uptake of ¹¹C-Choline in Mouse Atherosclerotic Plaques

Laitinen¹,

Luoto²,

Någren³

et al. 2010

J Nucl Med

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“…[ 11 C]choline is a PET cancer imaging agent used to study prostate cancer patients and breast cancer and prostate cancer animal models (Hara et al, 1998;Zheng et al, 2002Zheng et al, , 2004 was employed in the radiosynthesis of [ (NaI) flow detector showed that the radiochemical purity of [ 11 C]choline was >99%. The cold analytical HPLC chromatogram by UV flow detector showed that no precursor peak (R T DMAE = 2.43 min) was detected, which confirmed that the tracer [ 11 C]choline was completely separated from its unlabeled precursor DMAE through SiO 2 SPE technique.…”

Section: Resultsmentioning

confidence: 99%

“…Carbon-11 PET radiotracers were synthesized using two kinds of general labeling strategies with [ (Fei et al, 2004). It was prepared by O- 11 C-methylation of the precursor desmethyl-raclopride with [ 11 C]methyl triflate and purification with a semi-preparative HPLC method in 30-45% radiochemical yield, based on [ 11 C]methyl bromide, decay corrected to EOB.…”

Section: Resultsmentioning

confidence: 99%

Purification of carbon-11 PET radiotracers from unlabeled precursors by preparative HPLC and SPE

Zheng

Mock

2005

Biomed. Chromatogr.

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“…11 C-choline is transported into the tumor cell, phosphorylated by choline kinase a, and incorporated as phosphatidylcholine into the cell membrane (15). A major advantage of 11 C-choline is its low bladder activity, especially in comparison to 18 Flabeled tracers such as FDG.…”

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confidence: 99%

Assessment of PET Tracer Uptake in Hormone-Independent and Hormone-Dependent Xenograft Prostate Cancer Mouse Models

Kukuk¹,

Reischl²,

Raguin³

et al. 2011

J Nucl Med

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The pharmacokinetics of 18 F-fluorodeoxythymidine (FLT), 18 F-FDG, 11 C-choline, and 18 F-fluoroethylcholine (FEC) in 2 hormoneindependent (PC-3, DU145) and 2 hormone-dependent (CWR22, PAC120) prostate cancer xenograft mouse models were evaluated by PET and compared by immunohistochemistry. Further investigation was performed to determine whether PET can detect early changes in tumor metabolism after androgen ablation therapy through surgical castration. Methods: PET was performed on 4 consecutive days. In addition, the CWR22 and PAC120 tumor models were surgically castrated after the baseline measurement and imaged again after castration. The tracer uptake was analyzed using time-activity curves, percentage injected dose per volume (%ID/cm 3 ), and tumor-to-muscle ratio (T/M). Results: Regarding the hormone-independent prostate tumor models, 18 F-FLT showed the best T/M and highest %ID/cm 3 in PC-3 (2.97 6 0.63 %ID/cm 3 ) and DU145 (2.06 6 0.75 %ID/cm 3 ) tumors. 18 F-FDG seemed to be the tracer of choice for delineation of the PC-3 tumors but not for the DU145 tumors. Using 11 C-choline (PC-3: 1.33 6 0.29 %ID/cm 3 , DU145: 1.60 6 0.27 %ID/cm 3 ) and 18 F-FEC, we did not find any significant uptake in the tumors, compared with muscle tissue. Regarding the hormone-dependent prostate tumor models, the CWR22 model showed a highly significant (P , 0.01) decrease in tumor 18 F-FDG uptake from 4.11 6 1.29 % ID/cm 3 to 2.19 6 1.45 %ID/cm 3 after androgen ablation therapy. However, the 18 F-FLT, 11 C-choline, or 18 F-FEC tracers did not provide sufficient uptake or reliable information about therapy response in CWR22 tumors. The PAC120 model showed a significant increase in 18 F-FLT tumor uptake (P 5 0.015) after androgen ablation therapy. The accumulation of 18 F-FEC (before: 2.32 6 1.01 %ID/cm 3 , after: 1.36 6 0.39 %ID/cm 3 ) was found to be the next highest after 18 F-FDG (before: 2.45 6 0.93 %ID/cm 3 , after: 2.18 6 0.65 %ID/cm 3 ) in PAC120 tumors before castration and is better suited for monitoring therapy response. Conclusion: This comprehensive study in 2 hormone-dependent and 2 hormone-independent prostate tumor mouse models shows that 18 F-FLT and 18 F-FDG are the most appropriate tracers for delineation of PC-3, DU145 (except 18 F-FDG), and CWR22 tumors, but not for PAC120 tumors. 18 F-FEC and 11 Ccholine, in particular, revealed insufficient T/M ratio in the prostate tumor models. The results may indicate that radiolabeled choline and choline derivatives compete with a high concentration of the precursor dimethylaminoethanol, resulting in reduced uptake in small-rodent tumor models, a hypothesis that is currently under investigation in our laboratory.

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[11C]Choline as a PET biomarker for assessment of prostate cancer tumor models

Cited by 61 publications

References 28 publications

Uptake of ¹¹C-Choline in Mouse Atherosclerotic Plaques

Uptake of ¹¹C-Choline in Mouse Atherosclerotic Plaques

Purification of carbon-11 PET radiotracers from unlabeled precursors by preparative HPLC and SPE

Assessment of PET Tracer Uptake in Hormone-Independent and Hormone-Dependent Xenograft Prostate Cancer Mouse Models

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[11C]Choline as a PET biomarker for assessment of prostate cancer tumor models

Cited by 61 publications

References 28 publications

Uptake of 11C-Choline in Mouse Atherosclerotic Plaques

Uptake of 11C-Choline in Mouse Atherosclerotic Plaques

Purification of carbon-11 PET radiotracers from unlabeled precursors by preparative HPLC and SPE

Assessment of PET Tracer Uptake in Hormone-Independent and Hormone-Dependent Xenograft Prostate Cancer Mouse Models

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Uptake of ¹¹C-Choline in Mouse Atherosclerotic Plaques

Uptake of ¹¹C-Choline in Mouse Atherosclerotic Plaques