scholarly journals Siponimod (BAF312) penetrates, distributes, and acts in the central nervous system: Preclinical insights

2021 ◽  
Vol 7 (4) ◽  
pp. 205521732110491
Author(s):  
Marc Bigaud ◽  
Bettina Rudolph ◽  
Emmanuelle Briard ◽  
Christian Beerli ◽  
Andreas Hofmann ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Single Photon ◽  
Photon Emission ◽  
Whole Body ◽  
Blood Levels ◽  
Distribution Analysis ◽  
Single Photon Emission Ct ◽  
Cns Penetration ◽  
Exposure Ratio ◽  
Dose Dependent

Background Siponimod (BAF312), a selective S1P1/S1P5 agonist, reduces disability progression in secondary progressive MS. Recent observations suggest it could act via S1P1/S1P5-dependent anti-inflammatory and pro-myelination effects on CNS-resident cells. Objective Generate preclinical evidence confirming siponimod's CNS penetration and activity. Methods Siponimod's CNS penetration and distribution was explored in rodents and non-human primates (NHPs) using: Liquid Chromatography coupled to tandem Mass Spectrometry (LC-MS/MS), quantitative whole-body autoradiography (QWBA) using 14C-radiolabeled siponimod or non-invasive single-photon emission CT (SPECT) with a validated 123I-radiolabeled siponimod analog. Functional CNS activity was investigated by S1P1 receptor quantification in brain homogenates. Results In mice/rats, siponimod treatments achieved dose-dependent efficacy and dose-proportional increase in drug blood levels, with mean brain/blood drug-exposure ratio (Brain/BloodDER) of 6–7. Efficacy in rat brain tissues was revealed by a dose-dependent reduction in brain S1P1 levels. QWBA distribution analysis in rats indicated that [14C]siponimod related radioactivity could readily penetrate CNS, with particularly high uptakes in white matter of cerebellum, corpus callosum, and medulla oblongata versus lower exposures in other areas such as olfactory bulb. SPECT monitoring in NHPs revealed CNS distribution with a brain/bloodDER of ∼6, as in rodents. Conclusion Findings demonstrate siponimod's CNS penetration and distribution across species, with high translational potential to human.

scholarly journals Correlation of an Index-Lesion-Based SPECT Dosimetry Method with Mean Tumor Dose and Clinical Outcome after 177Lu-PSMA-617 Radioligand Therapy

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 428
Author(s):  
Friederike Völter ◽  
Lena Mittlmeier ◽  
Astrid Gosewisch ◽  
Julia Brosch-Lenz ◽  
Franz Josef Gildehaus ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Single Photon ◽  
Photon Emission ◽  
Whole Body ◽  
Biochemical Response ◽  
Emission Computed Tomography ◽  
Radioligand Therapy ◽  
Index Lesion ◽  
Recist 1.1 ◽  
Psma Pet

Background: Dosimetry can tailor prostate-specific membrane-antigen-targeted radioligand therapy (PSMA-RLT) for metastatic castration-resistant prostate cancer (mCRPC). However, whole-body tumor dosimetry is challenging in patients with a high tumor burden. We evaluate a simplified index-lesion-based single-photon emission computed tomography (SPECT) dosimetry method in correlation with clinical outcome. Methods: 30 mCRPC patients were included (median 71 years). The dosimetry was performed for the first cycle using quantitative 177Lu-SPECT. The response was evaluated using RECIST 1.1 and PERCIST criteria, as well as changes in PSMA-positive tumor volume (PSMA-TV) in post-therapy PSMA-PET and biochemical response according to PSA changes after two RLT cycles. Results: Mean tumor doses as well as index-lesion doses were significantly higher in PERCIST responders compared to non-responders (10.2 ± 12.0 Gy/GBq vs. 4.0 ± 2.9 Gy/GBq, p = 0.03 and 13.7 ± 14.2 Gy/GBq vs. 5.9 ± 4.4 Gy/GBq, p = 0.04, respectively). No significant differences in mean tumor and index lesion doses were observed between responders and non-responders according to RECIST 1.1, PSMA-TV, and biochemical response criteria. Conclusion: Compared to mean tumor doses on a patient level, single index-lesion-based SPECT dosimetry correlates equally well with the response to PSMA-RLT according to PERCIST criteria and may represent a fast and feasible dosimetry approach for clinical routine.

scholarly journals PET and SPECT Imaging of the EGFR Family (RTK Class I) in Oncology

2021 ◽  
Vol 22 (7) ◽  
pp. 3663
Author(s):  
Sara S. Rinne ◽  
Anna Orlova ◽  
Vladimir Tolmachev
Keyword(s):  
Single Photon ◽  
Photon Emission ◽  
Growth Factor Receptor ◽  
Spect Imaging ◽  
Emission Tomography ◽  
Class I ◽  
Whole Body ◽  
Her Family ◽  
Endogenous Expression ◽  
Egfr Family

The human epidermal growth factor receptor family (EGFR-family, other designations: HER family, RTK Class I) is strongly linked to oncogenic transformation. Its members are frequently overexpressed in cancer and have become attractive targets for cancer therapy. To ensure effective patient care, potential responders to HER-targeted therapy need to be identified. Radionuclide molecular imaging can be a key asset for the detection of overexpression of EGFR-family members. It meets the need for repeatable whole-body assessment of the molecular disease profile, solving problems of heterogeneity and expression alterations over time. Tracer development is a multifactorial process. The optimal tracer design depends on the application and the particular challenges of the molecular target (target expression in tumors, endogenous expression in healthy tissue, accessibility). We have herein summarized the recent preclinical and clinical data on agents for Positron Emission Tomography (PET) and Single Photon Emission Tomography (SPECT) imaging of EGFR-family receptors in oncology. Antibody-based tracers are still extensively investigated. However, their dominance starts to be challenged by a number of tracers based on different classes of targeting proteins. Among these, engineered scaffold proteins (ESP) and single domain antibodies (sdAb) show highly encouraging results in clinical studies marking a noticeable trend towards the use of smaller sized agents for HER imaging.

New Cardiac Cameras: Single-Photon Emission CT and PET

2014 ◽  
Vol 44 (4) ◽  
pp. 232-251 ◽  
Author(s):  
Piotr J. Slomka ◽  
Daniel S. Berman ◽  
Guido Germano
Keyword(s):  
Single Photon ◽  
Photon Emission ◽  
Single Photon Emission ◽  
Single Photon Emission Ct

scholarly journals Diagnostic Accuracy of Single Photon Emission CT in Alzheimer-Type Dementia.

1992 ◽  
Vol 29 (6) ◽  
pp. 463-468 ◽  
Author(s):  
Haruo Hanyu ◽  
Shinei Abe ◽  
Hisayuki Arai ◽  
Tetsuichi Asano ◽  
Toshihiko Iwamoto ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Single Photon ◽  
Photon Emission ◽  
Alzheimer Type ◽  
Single Photon Emission ◽  
Alzheimer Type Dementia ◽  
Single Photon Emission Ct

scholarly journals Limited value of99mTc depreotide single photon emission CT compared with CT for the evaluation of pulmonary lesions

2012 ◽  
Vol 85 (1015) ◽  
pp. e307-e313 ◽  
Author(s):  
S W Harders ◽  
H H Madsen ◽  
K Hjorthaug ◽  
M Rehling ◽  
T R Rasmussen ◽  
...  
Keyword(s):  
Single Photon ◽  
Photon Emission ◽  
Single Photon Emission ◽  
Pulmonary Lesions ◽  
Single Photon Emission Ct

scholarly journals Tc-99m HYNIC-TOC scintigraphy in dedifferentiated thyroid cancer

2019 ◽  
Vol 12 (4) ◽  
pp. e227910
Author(s):  
Kanhaiyalal Agrawal ◽  
P Sai Sradha Patro ◽  
C Preetam
Keyword(s):  
Thyroid Cancer ◽  
Single Photon ◽  
Somatostatin Receptor ◽  
Photon Emission ◽  
Peptide Receptor Radionuclide Therapy ◽  
Ct Imaging ◽  
Whole Body ◽  
Emission Computed Tomography ◽  
Serum Thyroglobulin ◽  
Pet Ct

There is literature evidence showing utility of somatostatin receptor (SSTR) positron emission tomography-CT (PET-CT) imaging in differentiated thyroid cancer with Thyroglobulin Elevated and Negative Iodine Scan (TENIS). These patients are less benefited with I-131 therapy and surgery remains only curable option if disease could be localised. If surgery is not feasible, other therapeutic options are not promising. However, if these patients show strongly positive SSTR imaging, then possibility of peptide receptor radionuclide therapy may be explored. As SSTR PET-CT imaging is expensive and not widely available, Technetium-99m (Tc-99m) hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC), which is a Single photon emission computed tomography (SPECT) tracer, can be used. We are documenting a case of raised serum thyroglobulin antibody and negative I-131 whole body scan with disease recurrence localised on Tc-99m HYNIC-TOC scan.

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