Characterization of acetate metabolism in tumor cells in relation to cell proliferation: Acetate metabolism in tumor cells

Yoshimoto, Mitsuyoshi; Waki, Atsuo; Yonekura, Yoshiharu; Sadato, Norihiro; Murata, Tetsuhito; Omata, Naoto; Takahashi, Norio; Welch, Michael J.; Fujibayashi, Yasuhisa

doi:10.1016/s0969-8051(00)00195-5

Cited by 219 publications

(131 citation statements)

References 18 publications

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“…VOI generation may be simplified, by generating them directly from the high-resolution anatomic images, which are fused to the metabolic images. FA will remain important for the generation of the tumor time-activity curve, as it highlights the metabolically active, and presumably proliferating, part of the tumor (29). The thresholding algorithm selected the most active part of the tumor/ prostate.…”

Section: Discussionmentioning

confidence: 99%

“…Some consider the increased citrate oxidation in the TCA cycle in neoplasms as the cause of enhanced acetate uptake (27), based on the view of the prostate as a citrate-producing gland (28). Others attribute the increased uptake to acetate retention in the prostate due to enhanced lipid synthesis (4), whereas the contribution as precursor (e.g., to amino and fatty acids, steroids) is usually not considered (29). In the current approach, our previously published myocardial model was adapted to the standard 3-compartment, 2-tissue model in oncology (Fig.…”

Section: Kinetic Modelmentioning

confidence: 99%

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1-¹¹C-Acetate Kinetics of Prostate Cancer

Schiepers¹,

Hoh²,

Nuyts³

et al. 2008

J Nucl Med

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18 F-FDG is in widespread use in cancer imaging but has limited utility in staging and monitoring of prostate cancer. 1-11 CLabeled acetate, a substrate for the citric acid cycle, is superior. The kinetics of prostate tumors were investigated. Methods: Ten patients with primary prostate cancer, 10 with recurrent tumor, and 2 men with benign prostate hypertrophy were studied. After administration of 5.5 MBq/kg 1-11 C-acetate, dynamic PET of the pelvis was acquired for 20 min. Images were reconstructed with iterative algorithms, and corrections for attenuation and scatter were applied. Factor analysis produced factor images, representing iliac vessels and the prostate from which blood-input and tissue-output functions were derived with simple thresholding techniques. Five different kinetic models were applied to the dynamic data to estimate the rate constants. Results: The standard 3-compartment, 2-tissue model was able to describe 1-11 C-acetate kinetics of the prostate. The model could be reduced to 3 parameters by setting the tissue blood fraction and release from the second tissue compartment (k 4 ) to zero. Correction for metabolites appeared to be necessary. This reduced model performed marginally better than a 2-compartment model. A significant correlation was found between the influx rate constant (K) and acetate uptake (standardized uptake value) for primary tumors (r 5 0.91), whereas there was no correlation for recurrent tumors (r 5 20.17). Patlak graphical analysis provided accurate parameter estimates. Conclusion: A 3-compartment, 3-parameter model is able to describe adequately the acetate kinetics in prostate cancer. Significant differences between primary and recurrent cancer were found for transport k 1 , influx K, distribution volume V d , as well as early (6-10 min) and late (15-20 min) 1-11 C-acetate uptake.

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Section: Discussionmentioning

confidence: 99%

Section: Kinetic Modelmentioning

confidence: 99%

1-¹¹C-Acetate Kinetics of Prostate Cancer

Schiepers¹,

Hoh²,

Nuyts³

et al. 2008

J Nucl Med

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“…Recently, it has been demonstrated that PET with AC, which is presumed to be an important probe of the anabolic pathway of metabolism in cancer tissue, shows marked uptake in renal cell carcinoma [8][9][10]. In our case, the longitudinal diameter of temporal bone lesions detected by MRI decreased from 14 mm prior to therapy to 11 mm, and the rest of the lesions detected by CT showed no change in size after the first cycle of sunitinib therapy.…”

Section: Discussionmentioning

confidence: 62%

Assessment of Therapeutic Effect of Sunitinib by 11C-Acetate PET Compared with FDG PET Imaging in a Patient with Metastatic Renal Cell Carcinoma

Oyama

Takahara

Hirabayashi

et al. 2011

Nucl Med Mol Imaging

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Although sunitinib shows a high response rate in patients with untreated metastatic renal cell carcinoma (mRCC), quite a few patients show no therapeutic effect. Therefore, it is crucial to distinguish the patients who respond to sunitinib from those who do not as early as possible after the administration of the therapy. We herein report a case of mRCC in which 11 C-acetate (AC) positron emission tomography (PET) showed an early therapeutic effect of sunitinib treatment 4 weeks after its administration.

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“…Notably, we have also shown that transient insulin deprivation modulates apoptotic signaling and suppresses acetate production by in vitro cultured human SCs [52,77]. Acetate is a central metabolite for the synthesis of fatty acids and cholesterol [78]. Thus, it may be expectable that the acetate produced by SCs is used by developing germ cells to sustain a high rate of lipids synthesis, which is an essential process for the constant membrane remodeling [52].…”

Section: Metabolic Cooperation In Testis Is Piv-otal For Spermatogenesismentioning

confidence: 85%

Metabolic Cooperation in Testis as a Pharmacological Target: From Disease to Contraception

Alves¹,

Dias²,

Silva³

et al. 2015

CMP

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Abstract:The development of a "male pill" to control fertility is still a major challenge. Although women have several options to play an active role in the couple family planning, men are very limited in terms of contraceptive methods. Several approaches have been proposed to develop a male contraceptive and can be divided in two major groups: hormonal and non-hormonal methods. Within the testis, the somatic Sertoli cell (SC) is known as the "nurse cell" since it provides the physical and nutritional support for the developing germ cells. Moreover, adjacent SCs form the Sertoli/blood testis barrier (BTB), which divides the seminiferous epithelium into the basal and the apical compartments, controlling the passage of substances to the site where germ cells develop. Among the several functions of SC, its metabolism and the production of lactate, acetate and other metabolic factors are essential for the normal occurrence of spermatogenesis. In the last years, several works have highlighted that the metabolic cooperation established between SCs and developing germ cells is compromised in several diseases associated with male subfertility/infertility. Notably, several metabolismassociated proteins are specifically expressed in the testis. Thus, there are several evidences illustrating that the control of male fertility can be achieved by targeting testicular cells metabolism. Herein, we discuss the metabolic cooperation in testis as a potential pharmacological target to counteract subfertility/infertility promoted by several diseases, particularly metabolic diseases. We also discuss how it can contribute to the development of a male contraceptive.

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Characterization of acetate metabolism in tumor cells in relation to cell proliferation: Acetate metabolism in tumor cells

Cited by 219 publications

References 18 publications

1-¹¹C-Acetate Kinetics of Prostate Cancer

1-¹¹C-Acetate Kinetics of Prostate Cancer

Assessment of Therapeutic Effect of Sunitinib by 11C-Acetate PET Compared with FDG PET Imaging in a Patient with Metastatic Renal Cell Carcinoma

Metabolic Cooperation in Testis as a Pharmacological Target: From Disease to Contraception

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Characterization of acetate metabolism in tumor cells in relation to cell proliferation: Acetate metabolism in tumor cells

Cited by 219 publications

References 18 publications

1-11C-Acetate Kinetics of Prostate Cancer

1-11C-Acetate Kinetics of Prostate Cancer

Assessment of Therapeutic Effect of Sunitinib by 11C-Acetate PET Compared with FDG PET Imaging in a Patient with Metastatic Renal Cell Carcinoma

Metabolic Cooperation in Testis as a Pharmacological Target: From Disease to Contraception

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1-¹¹C-Acetate Kinetics of Prostate Cancer

1-¹¹C-Acetate Kinetics of Prostate Cancer