Glucose Metabolism of Human Prostate Cancer Mouse Xenografts

Jadvar, Hossein; Li, Xiankui; Shahinian, Antranik; Park, Ryan; Tohme, Michel; Pinski, Jacek; Conti, Peter S.

doi:10.1162/15353500200505118

Cited by 40 publications

(43 citation statements)

References 40 publications

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“…Comparable results in CWR22 mice were found for 18 F-FLT before and after castration by Oyama et al (14). In CWR22 and PC-3 tumors, we found a 18 F-FDG T/M that was approximately a factor of 2 higher than the one reported by Jadvar et al (32). Krause et al showed in a PC-3 tumor model a T/M of 1.8 6 0.4 before treatment and was able to monitor with 11 C-choline a therapy response when using docetaxel (33).…”

Section: Discussioncontrasting

confidence: 48%

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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Section: Discussioncontrasting

confidence: 48%

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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“…Early changes in 18 F-FDG accumulation compared with volume changes were also seen by Leyton et al, who studied the efficacy of the cytotoxic agent cisplatin in an 18 F-FDG microPET study (13). Their study showed a difference in 18 F-FDG accumulation between the drugtreated and control groups at 24 h, whereas a difference in tumor volume was seen later at 48 h. Several other groups (8,(10)(11)(12) have tracked changes in tumor volume and 18 F-FDG accumulation; however, unlike the current study, no direct statistical comparisons were made in any of these prior studies to assess which changes occurred earlier.…”

Section: Ce-355621 Inhibits 18 F-fdg Accumulation In U87 Mg Xenograftsmentioning

confidence: 55%

“…With the development of microPET scanners for small animals (5), assessment of tumor xenograft mouse models with 18 F-FDG became possible for preclinical oncology research. Several authors have used 18 F-FDG microPET to assess various therapies in mouse tumor xenograft models (6)(7)(8)(9). In addition, several studies have compared 18 F-FDG microPET with an alternative proliferation tracer, 39-deoxy-39- 18 F-fluorothymidine ( 18 F-FLT), to assess tumor xenograft response to a variety of therapies (10)(11)(12)(13).…”

Section: Ce-355621 Is a Novel Monoclonal Antibody That Bindsmentioning

confidence: 99%

Preclinical Efficacy of the c-Met Inhibitor CE-355621 in a U87 MG Mouse Xenograft Model Evaluated by¹⁸F-FDG Small-Animal PET

Tseng¹,

Kang²,

Dandekar³

et al. 2007

J Nucl Med

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The purpose of this study was to evaluate the efficacy of CE-355621, a novel antibody against c-Met, in a subcutaneous U87 MG xenograft mouse model using 18 F-FDG small-animal PET. Methods: CE-355621 or control vehicle was administered intraperitoneally into nude mice (drug-treated group, n 5 12; control group, n 5 14) with U87 MG subcutaneous tumor xenografts. Drug efficacy was evaluated over 2 wk using 18 F-FDG smallanimal PET and compared with tumor volume growth curves. Results: The maximum %ID/g (percentage injected dose per gram of tissue) of 18 F-FDG accumulation in mice treated with CE-355621 remained essentially unchanged over 2 wk, whereas the %ID/g of the control tumors increased 66% compared with the baseline. Significant inhibition of 18 F-FDG accumulation was seen 3 d after drug treatment, which was earlier than the inhibition of tumor volume growth seen at 7 d after drug treatment. Conclusion: CE-355621 is an efficacious novel antineoplastic chemotherapeutic agent that inhibits 18 F-FDG accumulation earlier than tumor volume changes in a mouse xenograft model. These results support the use of 18 F-FDG PET to assess early tumor response for CE-355621.

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“…This further underlines the importance of considering the microenvironment, which potentially modulates intracellular metabolism [152]. Additionally, high grade (Gleason > 7) and castration-resistant tumors seem to reactivate glycolysis, since FDG-PET and FDG-PET/CT studies indicate an increased glucose uptake compared to benign and low stage prostate cancers [153][154][155][156][157]. Accordingly, prostate cancer is affected by 2-deoxyglucose [158][159][160].…”

Section: Later Stage Prostate Cancer Metabolismmentioning

confidence: 98%

Organ-Specific Cancer Metabolism and Its Potential for Therapy

Elia

Schmieder

Christen

et al. 2015

Handbook of Experimental Pharmacology

104

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KEYWORDS:Cancer metabolism, metabolic therapy, tissue specific metabolism, genetic drivers, epigenetic drivers, microenvironment, Warburg effect, reverse Warburg effect, mixed Warburg effect, triple-negative breast cancer, estrogen receptor positive breast cancer; prostate cancer, liver cancer, gluconeogenesis, fatty acid metabolism, glucose metabolism, glutamine metabolism, serine metabolism, metabolic normalization, metabolic depletion ABSTRACTTargeting the metabolism of cancer cells has the potential to lead to major advances in tumor therapy. Numerous promising metabolic drug targets have been identified. Yet, it has emerged that there is no singular metabolism that defines the oncogenic state of the cell. Rather, the metabolism of cancer cells is a function of the requirements of a tumor. Hence, the tissue of origin, the (epi)genetic drivers, aberrant signaling, and the microenvironment all together define these metabolic requirements. In this chapter we discuss in light of (epi)genetic, signaling, and environmental factors the diversity in cancer metabolism based on triple-negative and estrogen receptor positive breast cancer, early and late stage prostate cancer, and liver cancer. These types of cancer all display distinct and partially opposing metabolic behaviors (e.g. Warburg versus reverse Warburg metabolism). Yet, for each of the cancers their distinct metabolism supports the oncogenic phenotype. Finally, we will assess the therapeutic potential of metabolism based on the concepts of metabolic normalization and metabolic depletion.

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Glucose Metabolism of Human Prostate Cancer Mouse Xenografts

Cited by 40 publications

References 40 publications

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

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

Preclinical Efficacy of the c-Met Inhibitor CE-355621 in a U87 MG Mouse Xenograft Model Evaluated by¹⁸F-FDG Small-Animal PET

Organ-Specific Cancer Metabolism and Its Potential for Therapy

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Glucose Metabolism of Human Prostate Cancer Mouse Xenografts

Cited by 40 publications

References 40 publications

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

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

Preclinical Efficacy of the c-Met Inhibitor CE-355621 in a U87 MG Mouse Xenograft Model Evaluated by18F-FDG Small-Animal PET

Organ-Specific Cancer Metabolism and Its Potential for Therapy

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Preclinical Efficacy of the c-Met Inhibitor CE-355621 in a U87 MG Mouse Xenograft Model Evaluated by¹⁸F-FDG Small-Animal PET