Brain SPECT as an Imaging Biomarker for Evaluating Effects of Novel Treatments in Psychiatry–A Case Series

The difficulties of evaluating patients with complex neuropsychiatric conditions and prescribing appropriate treatments are well known. Imaging complements clinical assessments and allows a clinician to narrow the differential diagnosis by facilitating accurate and efficient evaluation. This is particularly relevant to neuropsychiatric conditions that are often diagnosed using a trial-and error process of exclusion. Single Photon Emission Computed Tomography (SPECT) is a functional brain imaging procedure that allows practitioners to measure the functional changes of gray matter structures based on regional cerebral blood flow (rCBF). The accurate diagnosis and treatment selection in psychiatry is challenging due to complex cases and frequent comorbidities. However, such complex neuropsychiatric conditions are increasingly benefitting from new treatment approaches, in addition to established medications. Among these are combination transcranial magnetic stimulation with ketamine infusions (CTK), hyperbaric oxygen therapy (HBOT) and perispinal administration of etanercept (PSE). This article provides readers with six case study examples that demonstrate how brain SPECT imaging can be used, both as a diagnostic tool, and as a potential biomarker for monitoring and evaluating novel treatments for patients with complex neuropsychiatric conditions. Six patients were assessed in our clinic and baseline brain SPECT imagesTourettes and a long history of alcohol were visually compared with SPECT images collected after periods of treatment with CTK or HBOT followed by PSE. This retrospective review demonstrates the clinical utility of these novel treatments and describes how SPECT imaging can complement standard diagnostic assessments. A novel display technique for SPECT images is described and we argue that SPECT imaging can be used for monitoring biomarker for clinical change.

Biological Distribution of Orally Administered [123I]MIBG for Estimating Gastrointestinal Tract Absorption

Gastrointestinal tract absorption of cationic anticancer drugs and medicines was estimated using whole-body imaging following oral [123I]MIBG administration. [123I]MIBG was added to cultures of human embryonic kidney (HEK)293 cells expressing human organic anion transporting polypeptide (OATP)2B1, carnitine/organic cation transporter (OCTN)1 and OCTN2, and organic cation transporter (OCT)1, OCT2, and OCT3 with and without cimetidine (an OCTN and OCT inhibitor) and L-carnitine (an OCTN inhibitor). Biodistribution analyses and single-photon emission computed tomography (SPECT) imaging in normal and dextran sodium sulfate (DSS)-induced experimental colitis mice were conducted using [123I]MIBG with and without cimetidine. [123I]MIBG uptake was significantly higher in HEK293/OCTN1, 2, and OCT1-3 cells than in mock cells. Uptake via OCTN was inhibited by L-carnitine, whereas OCT-mediated uptake was inhibited by cimetidine. Biodistribution analyses and SPECT imaging studies showed significantly lower accumulation of [123I]MIBG in the blood, heart, liver, and bladder in DSS-induced experimental colitis mice and mice with cimetidine loading compared with normal mice, whereas significantly higher accumulation in the stomach and kidney was observed after [123I]MIBG injection. [123I]MIBG imaging after oral administration can be used to estimate gastrointestinal absorption in the small intestine via OCTN and/or OCT by measuring radioactivity in the heart, liver, and bladder.

A New Way Forward: How Brain SPECT Imaging Can Improve Outcomes and Transform Mental Health Care Into Brain Health Care

In the past three decades, brain single-photon-emission-computed-tomography (SPECT) imaging has garnered a significant, evidence-based foundation for a wide array of indications relevant to the field of clinical psychiatry, including dementia, traumatic brain injuries, seizures, cerebrovascular disease, complex neuropsychiatric presentations, and treatment-resistant disorders. In clinical psychiatric practice, however, SPECT remains underutilized. Only a small percentage of psychiatric clinicians use brain imaging technology. In this article, the authors provide a rationale for shifting the paradigm to one that includes broader use of SPECT in the clinical psychiatric setting, primarily for patients with complex conditions. This paper will outline seven specific clinical applications. Adding neuroimaging tools like SPECT to day-to-day clinical practice can help move psychiatry forward by transforming mental health care, which can be stigmatizing and often shunned by the general public, to brain health care, which the authors argue will be more likely to be embraced by a larger group of people in need.

The GRP94 Inhibitor PU-WS13 Decreases M2-like Macrophages in Murine TNBC Tumors: A Pharmaco-Imaging Study with 99mTc-Tilmanocept SPECT

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancers and is not eligible for hormone and anti-HER2 therapies. Identifying therapeutic targets and associated biomarkers in TNBC is a clinical challenge to improve patients’ outcome and management. High infiltration of CD206+ M2-like macrophages in the tumor microenvironment (TME) indicates poor prognosis and survival in TNBC patients. As we previously showed that membrane expression of GRP94, an endoplasmic reticulum chaperone, was associated with the anti-inflammatory profile of human PBMC-derived M2 macrophages, we hypothesized that intra-tumoral CD206+ M2 macrophages expressing GRP94 may represent innovative targets in TNBC for theranostic purposes. We demonstrate in a preclinical model of 4T1 breast tumor-bearing BALB/c mice that (i) CD206-expressing M2-like macrophages in the TME of TNBC can be specifically detected and quantified using in vivo SPECT imaging with 99mTc-Tilmanocept, and (ii) the inhibition of GRP94 with the chemical inhibitor PU-WS13 induces a decrease in CD206-expressing M2-like macrophages in TME. This result correlated with reduced tumor growth and collagen content, as well as an increase in CD8+ cells in the TME. 99mTc-Tilmanocept SPECT imaging might represent an innovative non-invasive strategy to quantify CD206+ tumor-associated macrophages as a biomarker of anti-GRP94 therapy efficacy and TNBC tumor aggressiveness.