1-<sup>11</sup>C-Acetate as a PET Radiopharmaceutical for Imaging Fatty Acid Synthase Expression in Prostate Cancer

Vāvere, Amy L.; Kridel, Steven J.; Wheeler, Frances B.; Lewis, Jason S.

doi:10.2967/jnumed.107.046672

Cited by 158 publications

(128 citation statements)

References 41 publications

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“…Imaging with positron emission tomography tracers such as 11 C-acetate has been evaluated to monitor the lipogenic phenotype. 22 In the future, this animal model combined with 11 C-actetate/positron emission tomography tracer will provide not only a better understanding of the endogeneous lipogenesis in prostate cancer progression, but also a unique opportunity to validate the effectiveness of novel combinational therapy for translational research. …”

Section: Discussionmentioning

confidence: 99%

Targeted therapy with fatty acid synthase inhibitors in a human prostate carcinoma LNCaP/tk-luc-bearing animal model

Chen

Chang

Chuang

et al. 2012

Prostate Cancer Prostatic Dis

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BACKGROUND: Fatty acid synthase (FASN) is highly upregulated in human prostate carcinomas. Inhibition of FASN could arrest cell cycle and trigger apoptosis rapidly, implying the reliance of cancer cell survival on FASN. However, little is known about the effect of C75, a FASN inhibitor, and siFASN (that is, small interfering RNA targeted at FASN) on prostate cancer in living subjects. METHODS: We used C75 and siFASN to mediate the endogenous fatty acid metabolism in LNCaP human prostate cancer cells stably expressing herpes simplex virus type 1 thymidine kinase (HSV1-tk) and luciferase (luc) reporter genes, and assessed the effect of FASN blockade with different schedules of administration on tumor growth using noninvasive molecular imaging. RESULTS: FASN blockade exhibited the proliferative inhibition and induced G1-phase cell cycle arrest of LNCaP cells. For in vivo studies, the tumor growth inhibition by C75 (total 120 mg kg À1; 30 mg kg À1 once a week or 15 mg kg À1 twice a week for 4 weeks) and siFASN (1.4 mg kg À1 every alternate day up to 16 days) treatments were 80% and 70%, respectively, compared with that of the control. CONCLUSION:The results suggest that C75 may be superior to siFASN in anticancer effect on prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Targeted therapy with fatty acid synthase inhibitors in a human prostate carcinoma LNCaP/tk-luc-bearing animal model

Chen

Chang

Chuang

et al. 2012

Prostate Cancer Prostatic Dis

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“…Multiple other studies have evaluated the effectiveness of 11 C-acetate-PET in prostate cancer (14)(15)(16)(17)(18)(19)(20)(21)25). However, most of these studies have focused on patients with recurrent disease; have included heterogeneous patient populations (local recurrence, nodal disease, bone or visceral metastasis) or reference standards; and have been limited by small sample sizes.…”

Section: Discussionmentioning

confidence: 99%

“…Acetate enters the biochemical pathways of fatty acid metabolism, which are consistently upregulated in prostate cancer cell lines (14), and 11 C-acetate has minimal urinary excretion (15). Although multiple studies have demonstrated promising results with 11 C-acetate-PET for diagnosing local and distant disease after initial treatment failure (16)(17)(18)(19)(20), less is known about its value for initial prostate cancer staging (21).…”

Section: Introductionmentioning

confidence: 99%

2038 11c-Acetate Pet/Ct Before Radical Prostatectomy: Nodal Staging and Treatment Failure Prediction

et al. 2012

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Despite early detection programs, many patients with prostate cancer present with intermediate-or high-risk disease. We prospectively investigated whether 11 C-acetate PET/CT predicts lymphnode (LN) metastasis and treatment failure in men planned for radical prostatectomy.Methods-107 men with intermediate-or-high-risk localized prostate cancer with negative conventional imaging underwent PET/CT with 11 C-acetate. Five underwent LN staging only and 102 LN staging and prostatectomy. PET/CT findings were correlated with pathologic nodal status. Treatment-failure-free survival (TFFS) was estimated by Kaplan-Meier method. The ability of PET/CT to predict outcomes was evaluated by multivariate Cox proportional hazards analysis.Results-PET/CT was positive for pelvic LN or distant metastasis in 36 of 107 patients (33.6%). LN metastasis was present histopathologically in 25 (23.4%). The sensitivity, specificity, positiveand negative-predictive values of PET/CT for detecting LN metastasis were 68.0%, 78.1%, 48.6% and 88.9% respectively. 64 patients failed: 25 with metastasis, 17 with persistent postprostatectomy prostate specific antigen (PSA) >0.20 ng/mL, and 22 with biochemical recurrence (PSA >0.20 ng/mL after nadir) during follow-up for a median of 44.0 months. TFFS was worse in PET-positive than in PET-negative patients (p<0.0001) and in those with false-positive versus true-negative scans (p<0.01), suggesting that PET may have demonstrated nodal disease not removed surgically or identified pathologically. PET positivity independently predicted failure in preoperative (hazard ratio=3.26, p<0.0001) and postoperative (HR=3.07, p=0.0001) multivariate models.Conclusion-In patients planned for or completing prostatectomy, 11 C-acetate-PET/CT detects LN metastasis not identified by conventional imaging and independently predicts TTFS.

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“…The catabolic pathway influences as well, with acetate being able to metabolize into CO 2 via the Krebs cycle. Acetate is used as a substrate in some intracellular processes within the mitochondria by producing energy and in the cytosol in the synthesis of lipids 40,41 . The 11C-acetate is unable to distinguish between benign prostatic hyperplasia (BPH) and prostate cancer.…”

Section: C-acetatementioning

confidence: 99%

Radiotracers Used in Nuclear Medicine for Prostate Cancer Diagnosis and Follow-Up

García-Pérez¹,

Medina-Ornelas²

2022

GAMO

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Prostate cancer is the most common cause of cancer in males worldwide. Currently, imaging in prostate cancer has acquired great importance in staging, re-staging, treatment selection, and recurrence assessment. Molecular imaging with positron-emission tomography has enabled a personalized approach for these purposes. In addition to these clinical needs, there are growing perspectives and a challenge for new molecular imaging techniques, not only to detect metastatic disease, but also to provide relevant information on tumor biology and prognosis, and one of the greatest challenges for non-radioisotope imaging techniques is the ability to detect recurrence in patients with low levels of prostate-specific antigen. (creativecommons.org/licenses/by-nc-nd/4.0/).

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1-¹¹C-Acetate as a PET Radiopharmaceutical for Imaging Fatty Acid Synthase Expression in Prostate Cancer

Cited by 158 publications

References 41 publications

Targeted therapy with fatty acid synthase inhibitors in a human prostate carcinoma LNCaP/tk-luc-bearing animal model

Targeted therapy with fatty acid synthase inhibitors in a human prostate carcinoma LNCaP/tk-luc-bearing animal model

2038 11c-Acetate Pet/Ct Before Radical Prostatectomy: Nodal Staging and Treatment Failure Prediction

Radiotracers Used in Nuclear Medicine for Prostate Cancer Diagnosis and Follow-Up

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1-11C-Acetate as a PET Radiopharmaceutical for Imaging Fatty Acid Synthase Expression in Prostate Cancer

Cited by 158 publications

References 41 publications

Targeted therapy with fatty acid synthase inhibitors in a human prostate carcinoma LNCaP/tk-luc-bearing animal model

Targeted therapy with fatty acid synthase inhibitors in a human prostate carcinoma LNCaP/tk-luc-bearing animal model

2038 11c-Acetate Pet/Ct Before Radical Prostatectomy: Nodal Staging and Treatment Failure Prediction

Radiotracers Used in Nuclear Medicine for Prostate Cancer Diagnosis and Follow-Up

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1-¹¹C-Acetate as a PET Radiopharmaceutical for Imaging Fatty Acid Synthase Expression in Prostate Cancer