Deepak Behera, MD

Immunotherapy is becoming the mainstay for the treatment of a variety of malignancies, but only a subset of patients respond to treatment. Tumor-infiltrating CD8-positive (CD8+) T lymphocytes play a central role in anti-tumor immune responses. Non-invasive imaging of CD8+ T cells may provide new insights into the mechanisms of immunotherapy and potentially predict treatment response. We are studying the safety and utility of 89Zr-IAB22M2C, a radiolabeled minibody against CD8+ T cells, for… Show more

Immunotherapy is becoming the mainstay for the treatment of a variety of malignancies, but only a subset of patients respond to treatment. Tumor-infiltrating CD8-positive (CD8+) T lymphocytes play a central role in anti-tumor immune responses. Non-invasive imaging of CD8+ T cells may provide new insights into the mechanisms of immunotherapy and potentially predict treatment response. We are studying the safety and utility of 89Zr-IAB22M2C, a radiolabeled minibody against CD8+ T cells, for targeted imaging of CD8+ T cells in patients with cancer.

Results:
89Zr-IAB22M2C infusion was well tolerated with no immediate or delayed side effects observed after injection. Serum clearance was typically bi-exponential and dependent on the mass of minibody administered. Areas under the serum time-activity curve normalized to administered activity ranged from 1.3 h/l for 0.2 mg to 8.9 h/l for 10 mg. Biodistribution was dependent on the minibody mass administered. The highest uptake was always seen in spleen, followed by bone marrow. Liver uptake was more pronounced with higher minibody masses. Kidney uptake was typically low. Prominent uptake was seen in multiple normal lymph nodes as early as 2 h p.i., reaching peak levels by 24-48 h p.i. Uptake in tumor lesions was seen on imaging as early as 2 h p.i., with a majority of 89Zr-IAB22M2C-positive lesions detectable by 24 h. Lesions were visualized early in patients receiving treatment, with SUV ranging from 5.85-22.8 in 6 target lesions.

Conclusion:
89Zr-IAB22M2C imaging is safe and has favorable kinetics for early imaging. Biodistribution suggests successful targeting of CD8+ T cell-rich tissues. The observed targeting of tumor lesions suggests this may be informative for CD8+ T cell accumulation within tumors. Further evaluation is underway. Show less

Background
The cystine/glutamate antiporter (xc-) has been implicated in several neurological disorders and, specifically, in multiple sclerosis (MS) as a mediator of glutamate excitotoxicity and proinflammatory immune responses. We aimed to evaluate an xc-specific positron emission tomography (PET) radiotracer, (4S)-4-(3-[18F]fluoropropyl)-l-glutamate ([18F]FSPG), for its ability to allow non-invasive monitoring of xc- activity in a mouse model of MS.

Results
[18F]FSPG was found… Show more

Background
The cystine/glutamate antiporter (xc-) has been implicated in several neurological disorders and, specifically, in multiple sclerosis (MS) as a mediator of glutamate excitotoxicity and proinflammatory immune responses. We aimed to evaluate an xc-specific positron emission tomography (PET) radiotracer, (4S)-4-(3-[18F]fluoropropyl)-l-glutamate ([18F]FSPG), for its ability to allow non-invasive monitoring of xc- activity in a mouse model of MS.

Results
[18F]FSPG was found to be more sensitive than [18F]FDG at detecting pathological changes in the spinal cord and brain of EAE mice. Even before clinical signs of disease, a small but significant increase in [18F]FSPG signal was observed in the spinal cord of EAE mice compared to controls. This increase in PET signal became more pronounced in symptomatic EAE mice and was confirmed by ex vivo biodistribution and autoradiography. Likewise, in the brain of symptomatic EAE mice, [18F]FSPG uptake was significantly higher than controls, with the largest changes observed in the cerebellum. Western blot analyses of CNS tissues revealed a significant correlation between light chain of xc- (xCT) protein levels, the subunit of xc- credited with its transporter activity, and [18F]FSPG-PET signal. In vitro [18F]FSPG uptake studies suggest that both activated monocytes and T cells contribute to the observed in vivo PET signal.

Conclusion
These data highlight the promise of [18F]FSPG-PET as a technique to provide insights into neuroimmune interactions in MS and the in vivo role of xc- in the development and progression of this disease, thus warranting further investigation. Show less

Sigma-1 receptors (S1Rs) play an important role in many neurological disorders. Simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) with S1R radioligands may provide valuable information for diagnosing and guiding treatment for these diseases. Our previously reported S1R radioligand, [18F]FTC-146, demonstrated high affinity for the S1R (Ki = 0.0025 nM) and excellent selectivity for the S1R over the sigma-2 receptor (S2Rs; Ki = 364 nM) across several species (from… Show more

Sigma-1 receptors (S1Rs) play an important role in many neurological disorders. Simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) with S1R radioligands may provide valuable information for diagnosing and guiding treatment for these diseases. Our previously reported S1R radioligand, [18F]FTC-146, demonstrated high affinity for the S1R (Ki = 0.0025 nM) and excellent selectivity for the S1R over the sigma-2 receptor (S2Rs; Ki = 364 nM) across several species (from mouse to non-human primate). Herein, we report the clinical-grade radiochemistry filed with exploratory Investigational New Drug (eIND) and first-in-human PET/MRI evaluation of [18F]FTC-146. Show less

Objectives: Pain, whether it is back pain, arthritic, headache, etc., is now the most common reason to seek medical attention worldwide. The chronic pain sufferer, however, is currently faced with a lack of objective tools to identify the source of their pain. In chronic pain, neural tissues as well as any associated inflamed tissues, are hypermetabolic and, therefore, glucose avid. Accordingly, the overarching goal of this work is to develop a clinical [18F]FDG PET/MRI method to more… Show more

Objectives: Pain, whether it is back pain, arthritic, headache, etc., is now the most common reason to seek medical attention worldwide. The chronic pain sufferer, however, is currently faced with a lack of objective tools to identify the source of their pain. In chronic pain, neural tissues as well as any associated inflamed tissues, are hypermetabolic and, therefore, glucose avid. Accordingly, the overarching goal of this work is to develop a clinical [18F]FDG PET/MRI method to more accurately localize sites of increased tissue inflammation as it relates to sources of pain. The aims are to 1) determine whether imaging findings correlate with location of pain symptomology (radiologist unblinded to patient exam or history), 2) determine whether location of symptoms can be determined by MR imaging findings alone or PET/MRI imaging findings (radiologist blind to patient physical exam and history) and 3) to determine whether the imaging results affect current management decisions.

Conclusions: Our early experience suggests that [18F]FDG PET/MRI can identify hypermetabolic or inflammatory abnormalities in patients suffering from neuropathic pain. We have seen new plans implemented in 14 out of 16 patients, which were not anticipated by the referring physician. While initial results show some promise, the imaging data will have to be carefully scrutinized for non-specific uptake of [18F]FDG which can be observed in non-painful muscle recruitment, age-related arthritic changes and atherosclerotic vascular tissue. As we recruit more patients for the study, we will gain more insight into the use of this approach in helping patients with chronic neuropathic pain. Show less

Analgesic misuse is a major and expensive health issue. Among several others, inability to identify chronic pain generating foci is a contributing factor, leading to empirical treatments and interventions. Chronicity of pain occurs due to maladaptive cellular and molecular changes in the nervous system, which are divorced from initial injury, if any. Clinical imaging techniques used currently depend on discovering anatomic abnormalities, and, thus, are not sufficiently specific or sensitive to… Show more

Analgesic misuse is a major and expensive health issue. Among several others, inability to identify chronic pain generating foci is a contributing factor, leading to empirical treatments and interventions. Chronicity of pain occurs due to maladaptive cellular and molecular changes in the nervous system, which are divorced from initial injury, if any. Clinical imaging techniques used currently depend on discovering anatomic abnormalities, and, thus, are not sufficiently specific or sensitive to pin point causes of chronic pain. Molecular imaging can detect functional abnormalities that are a part of the maladaptive pathology of chronic pain syndromes. This chapter describes various molecular imaging techniques used to image pain processing and perception in the central nervous system, as well as pain generation in the peripheral nervous system. Show less

Molecular and cellular imaging of neuropathic pain, utilizing themyriad of receptors and
inflammatorymediators involved in nociceptive activity, is a promising approach toward
objectively identifying peripheral pain generators. Neuropathic conditions arise from
injured and inflamed nerves, which have been shown to elaborate severalmolecular and
cellular elements that give rise to the neuropathic phenotype and can be exploited for
imaging purposes. As such, in vivo approaches to… Show more

Molecular and cellular imaging of neuropathic pain, utilizing themyriad of receptors and
inflammatorymediators involved in nociceptive activity, is a promising approach toward
objectively identifying peripheral pain generators. Neuropathic conditions arise from
injured and inflamed nerves, which have been shown to elaborate severalmolecular and
cellular elements that give rise to the neuropathic phenotype and can be exploited for
imaging purposes. As such, in vivo approaches to image neuropathic pain mechanisms
include imaging voltage-gated sodium channels with radiolabeled saxitoxin, calcium
signaling with manganese-enhanced magnetic resonance imaging, and inflammatory
changes and nerve metabolism with 18F-fluorodeoxyglucose. Imaging approaches
exploiting other mediators of nociceptive activity, such as substance P (neurokinin-1)
receptor, sigma-1 receptor, and macrophages, have shown promising early advances in
animal models. By combining the sensitivity and specificity of molecular imaging with
the high anatomical, spatial and contrast resolution afforded by computed tomography
and MRI, radiologists can potentially identify sites of nerve injury or neuroinflammation
that are implicated as peripheral pain drivers with greater accuracy and confidence. In
addition to guiding therapy, these approaches will aid in new drug designs for analgesia
and more individualized treatment options. Show less

The noninvasive imaging of σ-1 receptors (S1Rs) could provide insight into their role in different diseases and lead to novel diagnostic/treatment strategies. The main objective of this study was to assess the S1R radiotracer (18)F-FTC-146 in rats. Preliminary squirrel monkey imaging and human serum/liver microsome studies were performed to gain information about the potential of (18)F-FTC-146 for eventual clinical translation.

Both chronic and neuropathic pain conditions are associated with increased expression of certain voltage-gated sodium ion channel (NaV) isoforms in peripheral sensory neurons. A method for noninvasive imaging of these channels could represent a powerful tool for investigating aberrant expression of NaV and its role in pain pathogenesis. Herein, we describe the synthesis and evaluation of a positron emission tomography (PET) radiotracer targeting NaVs, the design of which is based on the potent,… Show more

Both chronic and neuropathic pain conditions are associated with increased expression of certain voltage-gated sodium ion channel (NaV) isoforms in peripheral sensory neurons. A method for noninvasive imaging of these channels could represent a powerful tool for investigating aberrant expression of NaV and its role in pain pathogenesis. Herein, we describe the synthesis and evaluation of a positron emission tomography (PET) radiotracer targeting NaVs, the design of which is based on the potent, NaV-selective inhibitor saxitoxin. Both autoradiography analysis of sciatic nerves excised from injured rats as well as whole animal PET-MR imaging demonstrate that a systemically administered [18F]-labeled saxitoxin derivative concentrates at the site of nerve injury, consistent with upregulated sodium channel expression following axotomy. This type of PET agent has potential use for serial monitoring of channel expression levels at injured nerves throughout wound healing and/or following drug treatment. Such information may be correlated with pain behavioral analyses to help shed light on the complex molecular processes that underlie pain sensation. Show less

Knowledge of healthcare and wellness needs to be incessant. Owing to the concept of quantified self, the collaboration of technologies and healthcare ensure efficient self discovery, self awareness and self knowledge.

OBJECTIVE. A review of the innovative role molecular imaging plays in musculoskeletal radiology is provided. Musculoskeletal molecular imaging is under development in four key areas: imaging the activity of osteoblasts and osteoclasts, imaging of molecular and cellular biomarkers of arthritic joint destruction, cellular imaging of osteomyelitis, and imaging generators of musculoskeletal pain. CONCLUSION. Together, these applications suggest that next-generation musculoskeletal radiology will… Show more

OBJECTIVE. A review of the innovative role molecular imaging plays in musculoskeletal radiology is provided. Musculoskeletal molecular imaging is under development in four key areas: imaging the activity of osteoblasts and osteoclasts, imaging of molecular and cellular biomarkers of arthritic joint destruction, cellular imaging of osteomyelitis, and imaging generators of musculoskeletal pain. CONCLUSION. Together, these applications suggest that next-generation musculoskeletal radiology will facilitate quantitative visualization of molecular and cellular biomarkers, an advancement that appeared futuristic just a decade ago. Show less

Manganese-enhanced magnetic resonance imaging (MRI) is a surrogate method to measure calcium content in nervous system since manganese physiologically follows calcium. Manganese is detectable in MRI and therefore visualizes structures and cell populations that actively regulate calcium. Since calcium is actively recruited for the transmission of action potentials, our purpose is to validate manganese-enhanced MRI for detection of changes in lumbar nerves related to nociception. A neuropathic… Show more

Manganese-enhanced magnetic resonance imaging (MRI) is a surrogate method to measure calcium content in nervous system since manganese physiologically follows calcium. Manganese is detectable in MRI and therefore visualizes structures and cell populations that actively regulate calcium. Since calcium is actively recruited for the transmission of action potentials, our purpose is to validate manganese-enhanced MRI for detection of changes in lumbar nerves related to nociception. A neuropathic pain model was created by chronic constrictive injury of the left sciatic nerve of Sprague-Dawley rats. Behavioral measurements, using von Frey’s tests, confirmed the presence of significant allodynia in the left hind limb of animals in the injured group. T1-weighted fast spin echo images were obtained of the lumbar cord and plexus of animals with injured left sciatic nerve and uninjured animals (control) scanned in a 7 Tesla magnet after intraperitoneal manganese chloride administration four weeks after surgery. Lumbar nerve roots and sciatic nerves in the injured group show increased normalized manganese-enhanced MRI signal, representing manganese enhancement, compared to the control group. In conclusion, animals with neuropathic pain in the left hind limb show increased manganese uptake in not only the injured sciatic nerve but also in the contralateral uninjured sciatic nerve on manganese-enhanced MRI in vivo. Although poorly understood, this finding corroborates ex vivo finding of bilateral nociceptive-related molecular changes in the nervous system of unilateral pain models. Show less

We report a simple, efficient synthesis of novel 18F-labeled imaging agents based on YF3 nanoparticles. Targeting ligands and antitumor drug molecules can be introduced onto the YF3 nanoparticles in a one-pot synthesis. The 18F-labeling reaction proceeds in aqueous solutions at room temperature with excellent radiolabeling yields (>80%) in a very short time (5–10 min). 18F-labeled YF3 nanoparticles displayed high stability in mouse and human serum, and their application for mapping lymph… Show more

We report a simple, efficient synthesis of novel 18F-labeled imaging agents based on YF3 nanoparticles. Targeting ligands and antitumor drug molecules can be introduced onto the YF3 nanoparticles in a one-pot synthesis. The 18F-labeling reaction proceeds in aqueous solutions at room temperature with excellent radiolabeling yields (>80%) in a very short time (5–10 min). 18F-labeled YF3 nanoparticles displayed high stability in mouse and human serum, and their application for mapping lymph nodes in live rats after local injection has also been demonstrated. Show less

BACKGROUND: Minocycline has proven anti-nociceptive effects, and delays the development of allodynia/hyperalgesia after peripheral nerve injury. However, the mechanism by which this occurs remains unclear. Inflammatory cells, in particular macrophages, are critical components of the response to nerve injury. Using ultrasmall superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI) to monitor macrophage trafficking, the purpose of this project is to determine whether minocycline… Show more

BACKGROUND: Minocycline has proven anti-nociceptive effects, and delays the development of allodynia/hyperalgesia after peripheral nerve injury. However, the mechanism by which this occurs remains unclear. Inflammatory cells, in particular macrophages, are critical components of the response to nerve injury. Using ultrasmall superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI) to monitor macrophage trafficking, the purpose of this project is to determine whether minocycline modulates macrophage trafficking to the site of nerve injury in vivo and, in turn, results in altered pain thresholds.
RESULTS: A model of neuropathic pain was created using the Spared Nerve Injury (SNI) model that involves ligation of the left sciatic nerve in the left thigh of adult Sprague-Dawley rats. Animals with SNI and uninjured animals (control) were then injected with/without USPIOs and with/without minocycline. Bilateral sciatic nerves were scanned in a 7T magnet 7 days after USPIO administration. Pain behavior modulation was measured using the Von Frey filaments. Sciatic nerves were ultimately harvested at day 7 and stained for the presence of iron oxide-laden macrophages. Behavioral measurements confirmed the presence of allodynia in the neuropathic pain model (p<0.011). Decreased MR signal is observed in the SNI group that received USPIOs compared to the minocycline-treated SNI group that did/did not receive USPIOs (p<0.04). Histology confirmed the presence USPIOs at the nerve injury site in the SNI group without minocycline treatment.
CONCLUSION: Animals with neuropathic pain in the left hindpaw show increased trafficking of USPIO-laden macrophages to the site of sciatic nerve injury. Minocycline appears to retard the migration of macrophages to the nerve injury site, which may partly explain its anti-nociceptive effects. USPIO-MRI is an effective in vivo imaging tool to study the role of macrophages in the development of neuropathic pain. Show less

We demonstrated increased (18)F-FDG uptake in injured peripheral nerves in a model of neuropathic pain using small-animal PET/MRI.

METHODS:
A neuropathic pain model in rats was created by spared-nerve injury of the left sciatic nerve. Sham-operated rats without nerve injury were used as a control. The presence of pain was confirmed by testing for allodynia. Sequential small-animal (18)F-FDG PET and MRI scans of the thighs were obtained and coregistered. Autoradiography was performed… Show more

We demonstrated increased (18)F-FDG uptake in injured peripheral nerves in a model of neuropathic pain using small-animal PET/MRI.

METHODS:
A neuropathic pain model in rats was created by spared-nerve injury of the left sciatic nerve. Sham-operated rats without nerve injury were used as a control. The presence of pain was confirmed by testing for allodynia. Sequential small-animal (18)F-FDG PET and MRI scans of the thighs were obtained and coregistered. Autoradiography was performed on harvested nerves and muscle.

RESULTS:
The group with spared-nerve injury showed the development of allodynia in the operated limb (P < 0.001). Increased (18)F-FDG uptake was observed on both PET/MRI (P < 0.001) and autoradiography (P < 0.005) in the operated nerve in this group. (18)F-FDG uptake in the nerves correlated well with allodynia (ρ = -0.59; P < 0.024).

CONCLUSION:
Animals with neuropathic pain show increased (18)F-FDG uptake in the affected nerve. Small-animal PET/MRI can be effectively used to localize (18)F-FDG uptake in peripheral nerves. Show less

Existing treatment options for pain, such as the opioids, are not always effective and suffer from a wide range of side effects including potential for addiction. Saxitoxin (STX) is a highly potent naturally occurring sodium channel inhibitor that has been successfully employed in human clinical trials on >100 subjects for pain and certain neurological disorders. We hypothesized that our ability to prepare STX through de novo chemical synthesis would make possible the construction of… Show more

Existing treatment options for pain, such as the opioids, are not always effective and suffer from a wide range of side effects including potential for addiction. Saxitoxin (STX) is a highly potent naturally occurring sodium channel inhibitor that has been successfully employed in human clinical trials on >100 subjects for pain and certain neurological disorders. We hypothesized that our ability to prepare STX through de novo chemical synthesis would make possible the construction of modified forms of this compound having unique pharmacologic properties. Novel STXs were synthesized, characterized by patch clamp electrophysiology, and administered by local injection to the footpad of male Sprague Dawley rats. Antinociceptive efficacy and duration of action were measured through a variety of behavioral assays. Using this strategy, we have identified a STX derivative that provides up to six days of local analgesia in a rat nociception assay. We continue to evaluate the ADMET properties of our initial STX lead compounds through animal behavioral and radiological studies, and expect that such information will help guide the development of a STX-based therapeutic that offers improved efficacy and reduced side effects compared to existing treatment options for moderate to severe pain. Show less

The ability of divalent manganese to enter neurons via calcium channels makes manganese an excellent MRI contrast agent for the imaging of nociception, the afferent neuronal encoding of pain perception. There is growing evidence that nociceptive neurons possess increased expression and activity of calcium channels, which would allow for the selective accumulation of manganese at these sites. In this study, we show that oral manganese chloride leads to increased enhancement of peripheral nerves… Show more

The ability of divalent manganese to enter neurons via calcium channels makes manganese an excellent MRI contrast agent for the imaging of nociception, the afferent neuronal encoding of pain perception. There is growing evidence that nociceptive neurons possess increased expression and activity of calcium channels, which would allow for the selective accumulation of manganese at these sites. In this study, we show that oral manganese chloride leads to increased enhancement of peripheral nerves involved in nociception on T1-weighted MRI. Oral rather than intravenous administration was chosen for its potentially better safety profile, making it a better candidate for clinical translation with important applications, such as pain diagnosis, therapy and research. The spared nerve injury (SNI) model of neuropathic pain was used for the purposes of this study. SNI rats were given, sequentially, increasing amounts of manganese chloride (lowest, 2.29 mg/100 g weight; highest, 20.6 mg/100 g weight) with alanine and vitamin D3 by oral gavage. Compared with controls, SNI rats demonstrated increased signal-to-background ratios on T1-weighted fast spin echo MRI, which was confirmed by and correlated strongly with spectrometry measurements of nerve manganese concentration. We also found the difference between SNI and control rats to be greater at 48 h than at 24 h after dosing, indicating increased manganese retention in addition to increased manganese uptake in nociceptive nerves. This study demonstrates that oral manganese is a viable method for the imaging of nerves associated with increased nociceptive activity. Show less

Ovarian vein thrombosis (OVT) is a relatively uncommon but serious postpartum complication. Although infrequent, OVT may progress to involve the inferior vena cava, the renal vein or may cause sepsis and septic pulmonary embolism, all of which are potentially life-threatening. Clinical misdiagnosis is common, and, unfortunately, most affected women undergo laparotomy for possible appendicitis. We present an interesting case of OVT presenting as ureteral obstruction in a postpartum woman who was… Show more

Ovarian vein thrombosis (OVT) is a relatively uncommon but serious postpartum complication. Although infrequent, OVT may progress to involve the inferior vena cava, the renal vein or may cause sepsis and septic pulmonary embolism, all of which are potentially life-threatening. Clinical misdiagnosis is common, and, unfortunately, most affected women undergo laparotomy for possible appendicitis. We present an interesting case of OVT presenting as ureteral obstruction in a postpartum woman who was in her early 20s. Knowledge of this entity and clinical suspicion for its occurrence, in a puerperal patient with fever and abdominal pain not responding to antibiotics, should guide clinicians to appropriate diagnosis and treatment, avoiding misdiagnosis, unnecessary laparotomy and potential complications. Show less

A key challenge in developing nanoplatform-based molecular imaging is to achieve an optimal pharmacokinetic profile to allow sufficient targeting and to avoid rapid clearance by the reticuloendothelial system (RES). In the present study, iron oxide nanoparticles (IONPs) were coated with a PEGylated amphiphilic triblock copolymer, making them water soluble and function-extendable. These particles were then conjugated with a near-infrared fluorescent (NIRF) dye IRDye800 and cyclic… Show more

A key challenge in developing nanoplatform-based molecular imaging is to achieve an optimal pharmacokinetic profile to allow sufficient targeting and to avoid rapid clearance by the reticuloendothelial system (RES). In the present study, iron oxide nanoparticles (IONPs) were coated with a PEGylated amphiphilic triblock copolymer, making them water soluble and function-extendable. These particles were then conjugated with a near-infrared fluorescent (NIRF) dye IRDye800 and cyclic Arginine-Glycine-Aspartic acid (RGD) containing peptide c(RGDyK) for integrin alpha(v)beta(3) targeting. In vitro binding assays confirmed the integrin-specific association between the RGD-particle adducts and U87MG glioblastoma cells. Successful tumor homing in vivo was perceived in a subcutaneous U87MG glioblastoma xenograft model by both magnetic resonance imaging (MRI) and NIRF imaging. Ex vivo histopathological studies also revealed low particle accumulation in the liver, which was attributed to their compact hydrodynamic size and PEGylated coating. In conclusion, we have developed a novel RGD-IONP conjugate with excellent tumor integrin targeting efficiency and specificity as well as limited RES uptake for molecular MRI. Show less

Purpose: Understanding physiologic spinal cord glucose metabolism may provide insight regarding spinal cord diseases such as myelitis, trauma, and malignancy. We have refined characterized of the spinal cord and cauda equina by taking measurements at every slice of the whole body PET/CT through the length of the spine. Method and Materials: Approval was attained by our IRB. A retrospective review of 13 negative whole body 18F-FDG PET/CT studies with non-CNS cancers was performed. Studies with… Show more

Purpose: Understanding physiologic spinal cord glucose metabolism may provide insight regarding spinal cord diseases such as myelitis, trauma, and malignancy. We have refined characterized of the spinal cord and cauda equina by taking measurements at every slice of the whole body PET/CT through the length of the spine. Method and Materials: Approval was attained by our IRB. A retrospective review of 13 negative whole body 18F-FDG PET/CT studies with non-CNS cancers was performed. Studies with vertebral marrow hyperplasia, severe spinal arthritis, cervical/thoracic kyphosis or motion artifact had been previously excluded. Using the transaxial CT to define the spinal canal, oval region of interests (ROIs) of fixed dimensions were placed within the canal and excluded the bony elements of the spine. Corresponding PET measurements were obtained at every slice of the study C1 to S1. ROI measurements included average standard uptake values (SUVavg), which were standardized against L5 where minimal neural tissue was present. Data was analyzed using RT Image analysis software and statistical package Stata. Significance was p<0.005. Results: A significant decreasing cranial-caudal vertebral SUV trend with linear and quadratic effects relative to vertebral location has been identified. Standardized de-trended residuals from the regression were regressed on the individual vertebral segments, with L2 as the reference segment (because its mean residual was closest to zero). T12 was found to have a significantly different SUV. Conclusion: A predictable decreasing cranial-caudal pattern of 18-FDG uptake with a focal increase at T12 is observed in the spinal canal subjects. The nature of this pattern is unknown at this time, but may be related to relatively higher levels of grey matter and contributions from lower extremity peripheral nerves at this level. Show less