BMET-30ACCURACY OF SCREENING FOR BRAIN METASTASES WITH WHOLE-BODY FDG PET IN INITIAL STAGING OF NON-CENTRAL NERVOUS SYSTEM MALIGNANCY

Background:: Epigenetic dysfunction is implicated in many neurologic, psychiatric and oncologic diseases. Consequently, histone deacetylases (HDACs) inhibitors have been developed as therapeutic and imaging agents for these diseases. However, only a few radiotracers have been developed as HDACs imaging agents for the central nervous system (CNS). We report herein the synthesis and evaluation of [18F]INER-1577-3 ([18F]5) as an HDACs imaging agent for CNS. Methods:: [18F]INER-1577-3 ([18F]5) was synthesized by two methods: one-step (A) and two-step (B) methods. Briefly, radiofluorination of the corresponding precursors (11, 12) with K[18F]/K2.2.2 followed by purifications with HPLC gave ([18F]5). The quality of [18F]INER- 1577-3 synthesized by these methods was verified by HPLC and TLC as compared to an authentic sample. The inhibitions of [18F]INER-1577-3 and related HDACs inhibitors on tumor cells growth were carried out with breast cancer cell line 4T1 and MCF-7. The whole-body and brain uptake of [18F]INER-1577-3 in rats and AD mice were determined using a micro-PET scanner and the data was analyzed using PMOD. Results: : The radiochemical yield of [18F]INER-1577-3 synthesized by these two methods was 1.4 % (Method A) and 8.8% (Method B) (EOB), respectively. The synthesis time was 115 min and 100 min, respectively, from EOB. The inhibition studies showed that INER-1577-3 has a significant inhibitory effect in HDAC6 and HDAC8 but not HDAC2. PET studies in rats and AD mice showed a maximum at about 15 min postinjection for the whole brain of a rat (0.47 ± 0.03 %ID/g), SAMP8 mice (5.63 ± 1.09 %ID/g) and SAMR1 mice (7.23 ± 1.21 %ID/g). Conclusion:: This study showed that INER-1577-3 can inhibit tumor cell growth and is one of a few HDACs inhibitors that can penetrate the blood-brain barrier (BBB) and monitor HDAC activities in AD mice. Thus, [18F]INER-1577-3 may be a potent HDACs imaging agent, especially for CNS.

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Prospective comparison of the diagnostic accuracy of 18F-FDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients

European Radiology ◽

10.1007/s00330-021-07956-0 ◽

2021 ◽

Author(s):

Nils Martin Bruckmann ◽

Julian Kirchner ◽

Lale Umutlu ◽

Wolfgang Peter Fendler ◽

Robert Seifert ◽

...

Keyword(s):

Breast Cancer ◽

Bone Metastases ◽

Cancer Patients ◽

Bone Scintigraphy ◽

Fdg Pet ◽

Primary Breast Cancer ◽

Whole Body ◽

Newly Diagnosed ◽

Breast Cancer Patients ◽

Initial Staging

Abstract Objectives To compare the diagnostic performance of [18F]FDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients. Material and methods A cohort of 154 therapy-naive patients with newly diagnosed, histopathologically proven breast cancer was enrolled in this study prospectively. All patients underwent a whole-body [18F]FDG PET/MRI, computed tomography (CT) scan, and a bone scintigraphy prior to therapy. All datasets were evaluated regarding the presence of bone metastases. McNemar χ2 test was performed to compare sensitivity and specificity between the modalities. Results Forty-one bone metastases were present in 7/154 patients (4.5%). Both [18F]FDG PET/MRI and MRI alone were able to detect all of the patients with histopathologically proven bone metastases (sensitivity 100%; specificity 100%) and did not miss any of the 41 malignant lesions (sensitivity 100%). CT detected 5/7 patients (sensitivity 71.4%; specificity 98.6%) and 23/41 lesions (sensitivity 56.1%). Bone scintigraphy detected only 2/7 patients (sensitivity 28.6%) and 15/41 lesions (sensitivity 36.6%). Furthermore, CT and scintigraphy led to false-positive findings of bone metastases in 2 patients and in 1 patient, respectively. The sensitivity of PET/MRI and MRI alone was significantly better compared with CT (p < 0.01, difference 43.9%) and bone scintigraphy (p < 0.01, difference 63.4%). Conclusion [18F]FDG PET/MRI and MRI are significantly better than CT or bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. Both CT and bone scintigraphy show a substantially limited sensitivity in detection of bone metastases. Key Points • [18F]FDG PET/MRI and MRI alone are significantly superior to CT and bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. • Radiation-free whole-body MRI might serve as modality of choice in detection of bone metastases in breast cancer patients.

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18F-FDG PET Is an Independent Outcome Predictor in Primary Central Nervous System Lymphoma

Journal of Nuclear Medicine ◽

10.2967/jnumed.112.108654 ◽

2012 ◽

Vol 54 (2) ◽

pp. 184-191 ◽

Cited By ~ 23

Author(s):

B. Kasenda ◽

V. Haug ◽

E. Schorb ◽

K. Fritsch ◽

J. Finke ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Fdg Pet ◽

Central Nervous System Lymphoma ◽

Outcome Predictor ◽

18F Fdg

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Bone-brain crosstalk and potential associated diseases

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2016-0030 ◽

2016 ◽

Vol 28 (2) ◽

Cited By ~ 3

Author(s):

Audrey Rousseaud ◽

Stephanie Moriceau ◽

Mariana Ramos-Brossier ◽

Franck Oury

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Brain Development ◽

Cognitive Functions ◽

Intimate Relationship ◽

Whole Body ◽

Reciprocal Relationships ◽

Skeletal Homeostasis ◽

The Central Nervous System ◽

The Brain

AbstractReciprocal relationships between organs are essential to maintain whole body homeostasis. An exciting interplay between two apparently unrelated organs, the bone and the brain, has emerged recently. Indeed, it is now well established that the brain is a powerful regulator of skeletal homeostasis via a complex network of numerous players and pathways. In turn, bone via a bone-derived molecule, osteocalcin, appears as an important factor influencing the central nervous system by regulating brain development and several cognitive functions. In this paper we will discuss this complex and intimate relationship, as well as several pathologic conditions that may reinforce their potential interdependence.

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18F-FDG PET/CT in HIV-related central nervous system pathology

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-013-2448-1 ◽

2013 ◽

Vol 40 (9) ◽

pp. 1420-1427 ◽

Cited By ~ 17

Author(s):

Scarlett Lewitschnig ◽

Keerti Gedela ◽

Martina Toby ◽

Ranjababu Kulasegaram ◽

Mark Nelson ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Fdg Pet ◽

Central Nervous System Pathology ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

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The influence of brain metastases on the central nervous system effects of methylnaltrexone: a post hoc analysis of 3 randomized, double-blind studies

Supportive Care in Cancer ◽

10.1007/s00520-021-06070-7 ◽

2021 ◽

Author(s):

Darren M. Brenner ◽

Neal E. Slatkin ◽

Nancy Stambler ◽

Robert J. Israel ◽

Paul H. Coluzzi

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Brain Metastases ◽

Cancer Patients ◽

Opioid Withdrawal ◽

Double Blind ◽

Post Hoc Analysis ◽

Pain Scores ◽

Opioid Receptor Antagonists ◽

Post Hoc

Abstract Purpose Peripherally acting μ-opioid receptor antagonists such as methylnaltrexone (MNTX, Relistor®) are indicated for the treatment of opioid-induced constipation (OIC). The structural properties unique to MNTX restrict it from traversing the blood-brain barrier (BBB); however, the BBB may become more permeable in patients with brain metastases. We investigated whether the presence of brain metastases in cancer patients compromises the central effects of opioids among patients receiving MNTX for OIC. Methods This post hoc analysis of pooled data from 3 randomized, placebo-controlled trials included cancer patients with OIC who received MNTX or placebo. Endpoints included changes from baseline in pain scores, rescue-free laxation (RFL) within 4 or 24 h of the first dose, and treatment-emergent adverse events (TEAEs), including those potentially related to opioid withdrawal symptoms. Results Among 356 cancer patients in the pooled population, 47 (MNTX n = 27; placebo n = 20) had brain metastases and 309 (MNTX n = 172; placebo n = 137) did not have brain metastases. No significant differences in current pain, worst pain, or change in pain scores from baseline were observed between patients treated with MNTX or placebo. Among patients with brain metastases, a significantly greater proportion of patients who received MNTX versus placebo achieved an RFL within 4 h after the first dose (70.4% vs 15.0%, respectively, p = 0.0002). TEAEs were similar between treatment groups and were generally gastrointestinal in nature and not related to opioid withdrawal. Conclusion Focal disruptions of the BBB caused by brain metastases did not appear to alter central nervous system penetrance of MNTX.

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