Assessment of tumor hypoxia in spontaneous canine tumors after treatment with OMX, a novel H-NOX oxygen carrier, with [18F]FMISO PET/CT.

BACKGROUND: Hypoxia is a detrimental factor in solid tumors, leading to aggressiveness and therapy resistance. OMX, a tunable oxygen carrier from the heme nitric oxide/oxygen-binding (H-NOX) protein family, has the potential to reduce tumor hypoxia. [18F]Fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) is the most widely used and investigated method for non-invasive imaging of tumor hypoxia. In this study, we used [18F]FMISO PET/CT (computed tomography) to assess the effect of OMX on tumor hypoxia in spontaneous canine tumors. RESULTS: Thirteen canine patients with various tumors (n = 14) were randomly divided into blocks of two, with the treatment groups alternating between receiving intratumoral (IT) OMX injection (OMX IT group) and intravenous (IV) OMX injection (OMX IV group). Tumors were regarded as hypoxic if maximum tumor-to-muscle ratio (TMRmax) was greater than 1.4. In addition, hypoxic volume (HV) was defined as the region with tumor-to-muscle ratio greater than 1.4 on [18F]FMISO PET images. Hypoxia was detected in 6/7 tumors in the OMX IT group and 5/7 tumors in the OMX IV injection group. Although there was no significant difference in baseline hypoxia between the OMX IT and IV groups, the two groups showed different responses to OMX. In the OMX IV group, hypoxic tumors (n = 5) exhibited significant reductions in tumor hypoxia, as indicated by decreased TMRmax and HV in [18F]FMISO PET imaging after treatment. In contrast, hypoxic tumors in the OMX IT group (n = 6) displayed a significant increase in [18F]FMISO uptake and variable changes in TMRmax and HV. CONCLUSIONS: [18F]FMISO PET/CT imaging presents a promising non-invasive procedure for monitoring tumor hypoxia and assessing the efficacy of hypoxia-modulating therapies in canine patients. OMX has shown promising outcomes in reducing tumor hypoxia, especially when administered intravenously, as evident from reductions in both TMRmax and HV in [18F]FMISO PET imaging.

Biodistribution and image characteristics of 124 I-positron emission tomography in dogs with neuroendocrine neoplasia.

Radioactive iodine is frequently used for staging of human thyroid carcinomas. Iodine-124 scans performed using position emission tomography (PET) allow for more precise dosimetry of therapeutic radioiodine. The distribution of I-124 has not previously been described in veterinary medicine. The purpose of this prospective, exporatory, descriptive study is to evaluate the whole-body distribution of I-124 in dogs with suspected thyroid carcinoma. Ten dogs with either a cytologic diagnosis of a neuroendocrine neoplasm or biochemical hyperthyroidism were enrolled in a prospective clinical study. Whole-body I-124 PET/CT scans were performed and were evaluated for physiologic and pathologic uptake of I-124. The maximum and mean standardized uptake values (SUVmean) were recorded for several normal and abnormal tissues. Varying degrees of uptake were found in thyroid tumors (SUVmean = 66.37), ectopic thyroid masses (21.44), presumed metastatic lesions in lymph nodes (32.14), and the pulmonary parenchyma (4.50). In most dogs, physiologic uptake above background, measured in maximum SUV, was identified in parotid and mandibular salivary glands (14.00 and 1.57) the urinary tract (1.83), the gastrointestinal tract (19.90 stomach, 6.15 colon), the liver (1.41), and the heart (1.88). Occasionally, uptake was identified in the nasolacrimal duct (3.42), salivary duct (2.73), gallbladder (2.68), and anal gland (2.22). Physiologic uptake was also identified in normal thyroid glands and ectopic thyroid tissue. This study provides a baseline of pathologic and physiologic uptake of I-124 in dogs with thyroid carcinoma, to guide interpretation of future studies.

Comparison of 18F-sodium fluoride positron emission tomography and CT: An exploratory study in 12 dogs with elbow pain.

18F-Sodium Fluoride (18F-NaF) positron emission tomography (PET) provides high resolution functional information about bone activity and can be fused with CT images to improve three-dimensional localization and characterization of lesions. This prospective, observational study assessed 18F-NaF PET-CT for imaging of canine elbows, compared PET with CT findings, and assessed correlation with lameness. Twelve patients with elbow pain were included. Cases included primarily young, large breed dogs. A three-level clinical lameness score was assigned to each forelimb. All dogs had bilateral elbow joints imaged with CT and PET under general anesthesia, approximately 1.5 h after intravenous injection of 3 MBq/kg of 18F-NaF. Imaging findings were independently reviewed by two radiologists using a three-level scoring scheme over nine anatomical regions in the elbow. PET imaging identified areas of bone activity where minimal change was identified on CT. PET imaging also demonstrated absence of uptake in areas where modeling was present on CT. A stronger correlation was observed between clinical grades and PET scores (r2  = 0.38, P = .001) than between clinical grades and CT scores (r2  = 0.17, P = .048). The total PET scores were significantly different for each clinical grade (P = .013) but total CT scores did not differ (P = .139). This exploratory study suggests that PET improves the ability to detect lesions and to determine the clinical significance of CT findings in dogs with elbow pain.

The use of fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography as an effective method for staging in dogs with primary appendicular osteosarcoma.

Fluorine-18-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) has been utilized in veterinary medicine to improve the detection and characterization of primary, recurrent, and secondary neoplasms; but its use as a staging tool for dogs diagnosed with appendicular osteosarcoma has not been published. The purpose of this retrospective, case series, descriptive study was to detail the use of 18 F-FDG PET/CT for staging a population of dogs with appendicular osteosarcoma, report the detection rate of secondary neoplastic lesions, and compare findings with published detection rates for other historically used imaging modalities. Seventy-one client-owned dogs with a confirmed diagnosis of appendicular osteosarcoma and staged with a whole-body 18 F-FDG PET/CT scan near the time of initial diagnosis were included. Each PET/CT study was re-evaluated for malignancy distinct from the primary disease entity based on a collective qualitative and quantitative assessment of 18 F-FDG uptake, CT appearance, and contrast enhancement characteristics. Following re-evaluation of each study, information pertaining to tissue sampling performed on identified lesions was retrieved from the medical record when available. Staging with 18 F-FDG PET/CT identified 17 of 71 (23.9%) and 12 of 71 (16.3%) dogs with a high suspicion or confirmation of a metastatic or comorbid malignant neoplasm respectively, with eight of 71 (11.3%) having both metastatic and comorbid lesions. The results of this study are suggestive that 18 F-FDG PET/CT is effective in identifying both osseous and soft tissue secondary neoplastic lesions in dogs afflicted with appendicular osteosarcoma, yielding an increased detection rate of all lesions compared those previously reported for skeletal scintigraphy or whole-body CT.

Flourine-18 fluorodeoxyglucose positron emission tomography imaging exhibits increased SUVmax at the level of the spinal intumescence in normal dogs.

Positron emission tomography (PET) imaging utilizing fluorine-18 labeled fluorodeoxyglucose is a relatively new imaging modality in veterinary medicine that is becoming more common for oncological staging and for musculoskeletal imaging. Thus, it is important to identify the normal variations on PET imaging that may be mistaken for pathology. Variation in standardized uptake values (SUVmax) have been anecdotally identified in the spinal cord of dogs undergoing fluorodeoxyglucose (FDG) PET-CT examinations for oncological staging, with notable increase in SUVmax values identified in the region of the cervical and lumbar spinal intumescences. The aim of this retrospective, analytical study was to compare the SUVmax values at four different locations throughout the spinal cord (C3, C5-T1, T13, and L3-S1) of a group of dogs with no evidence of neurologic disease and compare those findings to histologic specimens from dogs euthanized for unrelated disease. SUVmax values were significantly higher at the cervical and lumbar intumescences in comparison to the control regions (P < .0001 and P < .0001, respectively). Neuronal count and spinal cord gray matter area were also significantly greater at the cervical and lumbar intumescences (neuronal count P = .0025 and P = .0001; area P = .0004 and P = .0009, respectively) while overall neuronal density was lower (P = .003 and P = .028, respectively). We presume the increased SUVmax values at the spinal cord intumescences are the result of overall increased neuron count, increased proportion of gray matter, and increased spinal cord gray matter area. These findings will aid in the interpretation of future PET-CT studies and hopefully prevent the misdiagnosis of spinal cord disease in normal canines.

Fluorine-18-fluoro-2-deoxy-d-glucose PET-CT aids in detection of soft-tissue injuries for dogs with thoracic or pelvic limb lameness.

Fluorine-18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) provides physiologic images of tissues based on their glucose metabolism. The combination of FDG PET and CT (FDG PET-CT) has been utilized in human musculoskeletal imaging to localize soft tissue lesions, however, this modality has not been thoroughly investigated for the diagnosis of canine lameness. This prospective, descriptive study evaluated FDG PET-CT findings in 25 client-owned dogs with inconclusive origin of thoracic or pelvic limb lameness (thoracic limb n = 15/25, 60%; pelvic limb n = 6/25, 24%; and combination of both limbs n = 4/25, 16%). We hypothesized that FDG PET-CT would aid the detection of soft tissue lesions not visible with other imaging modalities. Combined FDG PET-CT detected soft tissue lesions in 40% (n = 10/25) and osteoarthritis in 64% (n = 16/25) of the patients. FDG PET detected more soft tissue lesions than contrast-enhanced CT (n = 15/15, 100% and n = 12/15, 80%, respectively), while CT identified more osteoarthritis lesions than FDG PET (n = 26/26, 100% and n = 18/26, 69%, respectively). The three imaging-diagnoses based on the FDG PET component included the following: flexor carpi ulnaris muscle tear, psoas major myopathy, and tarsal desmopathy. No diagnosis for the lameness was obtained in three dogs. Findings supported FDG PET-CT as a useful adjunct imaging modality for detection of certain soft tissue injuries of the musculoskeletal system. Combined FDG PET-CT should be considered for cases where the cause of lameness is thought to be of soft tissue origin and cannot be diagnosed by conventional means.

18 F-FDG-PET/CT as adjunctive diagnostic modalities in canine fever of unknown origin.

Fever of unknown origin (FUO) is a persistent or recurrent fever for which the underlying source has not been identified despite diagnostic investigation. In people, 18 F-fluoro-2-deoxyglucose positron emission tomography (18 F-FDG-PET) alone or in combination with computed tomography (CT) is often beneficial in detecting the source of fever when other diagnostics have failed. Veterinary reports describing use of these modalities in animals with fever of unknown origin are currently lacking. Aims of this retrospective case series were to describe 18 F-FDG-PET or 18 F-FDG-PET/CT findings in a group of dogs with fever of unknown origin. Dogs presenting to a single center between April 2012 and August 2015 were included. A total of four dogs met inclusion criteria and underwent either positron emission tomography (n = 2) or positron emission tomography/CT (n = 2) as a part of their diagnostic investigation. All subjects underwent extensive diagnostic testing prior to 18 F-FDG-PET/CT. Initial diagnostic evaluation failed to identify either a cause of fever or an anatomic location of disease in these four dogs. In each dog, positron emission tomography or positron emission tomography/CT was either able to localize or rule out the presence of focal lesion thereby allowing for directed sampling and/or informed disease treatment. Follow up 18 F-FDG-PET/CT scans performed in two patients showed improvement of observed abnormalities (n = 1) or detected recurrence of disease allowing for repeated treatment before clinical signs recurred (n = 1). Fever resolved after specific treatment in each dog. Findings from the current study supported the use of positron emission tomography or positron emission tomography/CT as adjunctive imaging modalities for diagnosis and gauging response to therapy in dogs with fever of unknown origin.

Pilot study utilizing Fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography for glycolytic phenotyping of canine mast cell tumors.

The goal of this prospective pilot study was to use naturally occurring canine mast cell tumors of various grades and stages as a model for attempting to determine how glucose uptake and markers of biologic behavior are correlated. It was hypothesized that enhanced glucose uptake, as measured by 2-[fluorine-18]fluoro-d-glucose-positron emission tomography/computed tomography (F18 FDG PET-CT), would correlate with histologic grade. Dogs were recruited for this study from a population referred for treatment of cytologically or histologically confirmed mast cell tumors. Patients were staged utilizing standard of care methods (abdominal ultrasound and three view thoracic radiographs), followed by a whole body F18 FDG PET-CT. Results of the F18 FDG PET-CT were analyzed for possible metastasis and standard uptake value maximum (SUVmax ) of identified lesions. Incisional or excisional biopsies of the accessible mast cell tumors were obtained and histology performed. Results were then analyzed to look for a possible correlation between the grade of mast cell tumors and SUVmax . A total of nine animals were included in the sample. Findings indicated that there was a correlation between grade of mast cell tumors and SUVmax as determined by F18 FDG PET-CT (p-value = 0.073, significance ≤ 0.1). Based on the limited power of this study, it is felt that further research to examine the relationship between glucose utilization and biologic aggressiveness in canine mast cell tumors is warranted. This study was unable to show that F18 FDG PET-CT was a better staging tool than standard of care methods.

A prototype PET/SPECT/X-rays scanner dedicated for whole body small animal studies.

OBJECTIVE: To present a prototype tri-modal imaging system, consisting of a single photon emission computed tomography (SPET), a positron emission tomography (PET), and a computed tomography (CT) subsystem, evaluated in planar mode. MATERIALS AND METHODS: The subsystems are mounted on a rotating gantry, so as to be able to allow tomographic imaging in the future. The system, designed and constructed by our group, allows whole body mouse imaging of competent performance and is currently, to the best of our knowledge, unequaled in a national and regional level. The SPET camera is based on two Position Sensitive Photomultiplier Tubes (PSPMT), coupled to a pixilated Sodium Iodide activated with Thallium (NaI(Tl)) scintillator, having an active area of 5x10cm2. The dual head PET camera is also based on two pairs of PSPMT, coupled to pixelated berillium germanium oxide (BGO) scintillators, having an active area of 5x10cm2. The X-rays system consists of a micro focus X-rays tube and a complementary metal-oxide-semiconductor (CMOS) detector, having an active area of 12x12cm2. RESULTS: The scintigraphic mode has a spatial resolution of 1.88mm full width at half maximum (FWHM) and a sensitivity of 107.5cpm/0.037MBq at the collimator surface. The coincidence PET mode has an average spatial resolution of 3.5mm (FWHM) and a peak sensitivity of 29.9cpm/0.037MBq. The X-rays spatial resolution is 3.5lp/mm and the contrast discrimination function value is lower than 2%. CONCLUSION: A compact tri-modal system was successfully built and evaluated for planar mode operation. The system has an efficient performance, allowing accurate and informative anatomical and functional imaging, as well as semi-quantitative results. Compared to other available systems, it provides a moderate but comparable performance, at a fraction of the cost and complexity. It is fully open, scalable and its main purpose is to support groups on a national and regional level and provide an open technological platform to study different detector components and acquisition strategies.

Treatment of extraskeletal osteosarcoma at a previous injection site resulting in prolonged survival in 1 dog.

A rare presentation of an extraskeletal osteosarcoma at a previous interscapular injection site in a dog is described. Treatment included surgical excision of the tumor followed by 6 rounds of intravenous carboplatin, oral toceranib, and cyclophosphamide. The dog survived for 20.5 months after diagnosis despite early development of pulmonary metastases.

Traitement d'un ostéosarcome extrasquelettique à un site d'injection antérieur produisant une survie prolongée chez un chien. Ce rapport décrit une rare présentation d'un ostéosarcome extrasquelettique à un site d'injection interscapulaire antérieur chez un chien. Le traitement a inclus l'excision chirurgicale de la tumeur suivie de six séries de traitement de carboplatine intraveineuse, de tocéranib oral et de cyclophosphamide. Le chien a survécu pendant 20,5 mois après le diagnostic malgré le développement précoce de métastases pulmonaires.(Traduit par Isabelle Vallières).

Use of 18 F-2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography for staging thyroid carcinoma in a cat.

Thyroid nodules are common in older cats and are mostly benign; however, carcinomas may occur infrequently. In cats, thyroid carcinomas tend to be highly metastatic. The role of 18 F-2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) in human thyroid carcinoma has been well established. However, guidelines have not yet been established for veterinary medicine. Metastasis assessment has typically been performed using CT in veterinary medicine; however, it is poorly sensitive in detecting regional lymph nodes or distant metastases if these lesions are not abnormally contrast-enhanced, enlarged or cause overt mass effects. This case suggested that FDG PET/CT may be used for staging feline thyroid carcinoma, and the results contributed to treatment recommendations.

Positive-pressure breath-hold positron emission tomography/computed tomography is feasible for respiratory-induced artifact reduction in healthy dogs.

OBJECTIVE: To perform qualitative and quantitative analysis of positron emission tomography (PET)/CT images using spontaneous ventilation (SV) and positive-pressure breath-hold (PPBH) techniques in order to demonstrate the feasibility of PPBH PET/CT to decrease respiration-induced artifacts. ANIMALS: 5 healthy female mixed-breed dogs. PROCEDURES: 2-([18F]fluoro)-2-deoxy-D-glucose (was administered to each anesthetized dog. An SV PET/CT scan was performed from the head to the femur using 8 bed positions (3 min/bed) followed by a PPBH scan centered over the diaphragm with a single bed position (1.5 min/bed). PET image quality, the misalignment of organs between PET and CT images, and standardized uptake values (SUVs) of liver adjacent to diaphragm were compared between SV and PPBH. RESULTS: Overall image quality and conspicuity of anatomic structures were superior in PPBH than in SV PET images. PPBH induced significantly less misalignment of the liver and diaphragm in all planes compared to SV. For the gall bladder, PPBH showed significantly less misalignment than SV only in the transverse plane. The maximum SUV in all of the liver areas was significantly higher with PPBH compared to SV. PPBH exhibited significantly higher mean SUV in the liver adjacent to the left diaphragmatic dome and left lateral border and higher minimum SUV only in the liver adjacent to the left diaphragmatic dome. CLINICAL RELEVANCE: PPBH was demonstrated to be a feasible PET/CT protocol with higher PET image quality, less organ misalignment on fused PET/CT, and more accurate SUVs of the liver compared to SV PET/CT in healthy dogs.

Staging canine patients with appendicular osteosarcoma utilizing fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography compared to whole body computed tomography.

Few studies have investigated the diagnostic performance of fluorine-18-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) for staging veterinary patients with appendicular osteosarcoma. The purpose of this study was to evaluate the efficacy of 18 F-FDG-PET/CT compared to whole-body CT (WBCT) for staging canine patients with appendicular osteosarcoma. The 18 F-FDG-PET/CT imaging studies of 66 dogs with appendicular osteosarcoma were anonymized and separated into two detached studies (one with whole body pre- and post-contrast CT images and the other with the whole body pre- and post-contrast CT images with the associated 18 F-FDG-PET overlay). Image assessment was performed retrospectively by five board-certified veterinary radiologists. The radiologists were instructed to assign a predefined categorical score (1-4) to each pre-designated anatomic region based on a devised lesional scoring system. A score of 1 was normal, 2 abnormal but not neoplastic, 3 abnormal and concerning for neoplasia, and 4 abnormal, most likely neoplastic. Overall, the likelihood of detection of '3 or 4' was found to be significantly higher with 18 F-FDG PET/CT when compared to WBCT after adjusting for the effect of evaluator and the subject. Most significantly, 13 osseous lesions concerning for metastasis (scored 3-4) were identified in 10/66 dogs by at least one reviewer on 18 F-FDG PET/CT, which were not identified by any reviewer on WBCT. Additionally, four comorbid neoplastic lesions were identified with 18 F-FDG PET/CT and not with WBCT. The results of this study suggest that 18 F-FDG PET/CT is more efficacious in detecting metastatic and comorbid neoplastic lesions compared to WBCT in dogs with appendicular osteosarcoma.

Fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography for staging of canine insulinoma: 3 cases (2019-2020).

OBJECTIVES: Canine insulinomas are uncommon malignant functional pancreatic neuroendocrine tumours with a high metastatic rate. Diagnostic imaging aids with staging and surgical planning of these tumours; however, identification is unpredictable across modalities. High-grade human pancreatic neuroendocrine tumours display increased avidity on 18 F-fluorodeoxyglucose positron emission tomography-CT. MATERIALS AND METHODS: Dogs with clinicopathologic findings consistent with pancreatic insulinoma were prospectively enrolled. Patients underwent 18 F-fluorodeoxyglucose positron emission tomography-CT and CT angiography, followed by exploratory laparotomy. RESULTS: Three patients met the inclusion criteria and had histologically confirmed insulinomas. Both metastatic lesions in patient 1 were mildly avid (SUVmax 2.79 and 3.01). In patient 2, the primary pancreatic insulinoma was minimally avid (SUVmax 2.16). The primary pancreatic lesion in patient 3 had similar avidity to normal pancreatic parenchyma (SUVmax 1.54) and was undetected on 18 F-fluorodeoxyglucose positron emission tomography-CT. Insulinomas demonstrated variable attenuation and contrast enhancement patterns on CT angiography and certain lesions were more conspicuous than on 18 F-fluorodeoxyglucose positron emission tomography-CT. Two metastatic lesions not visible on either imaging modality were discovered in patient 2 at surgery. CLINICAL SIGNIFICANCE: Canine insulinomas were inconsistently avid on 18 F-fluorodeoxyglucose positron emission tomography-CT. This finding is likely attributable to the confounding clinicopathological features and multifaceted transformation of these tumours, in addition to the influence of variable tumour size, composition and vascularity. Unpredictable tumoural avidity limits the value of 18 F-fluorodeoxyglucose positron emission tomography-CT for staging canine insulinomas.

Retrospective analysis of use of fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) for detection of metastatic lymph nodes in dogs diagnosed with appendicular osteosarcoma.

The purpose of this retrospective analysis was to determine if fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) could potentially be an accurate staging tool for detecting metastatic lymph nodes in dogs with appendicular osteosarcoma based on the quantitative measurement of the maximum standard uptake value (SUVmax) of lymph nodes. A total of 53 dogs were identified that presented for staging via 18F-FDG PET/CT for primary appendicular osteosarcoma. Patients were categorized according to lymph node status of having either metastatic or non-metastatic nodes based on cytological or histological analysis. Maximum standard uptake (SUVmax) values of the sampled lymph node(s) were recorded and 3/77 (3.9%) of sampled lymph nodes were confirmed metastatic. A Mann-Whitney test revealed a statistical difference in the SUVmax of the metastatic versus non-metastatic lymph nodes [median: 6.6 to 95% confidence interval (CI): 2.56 to 14.37 versus 2.18 95% CI: 2.32 to 3.17, respectively, P-value = 0.05]. This retrospective analysis revealed a significant difference in the SUVmax as measured on 18F-FDG PET/CT between metastatic lymph nodes and non-metastatic lymph nodes in canine patients afflicted with appendicular osteosarcoma, in spite of the small numbers analyzed. While these results are promising, they should be interpreted with caution and further studies are justified.

Le but de cette analyse rétrospective était de déterminer si la tomographie par émission de positons avec le fluor-18 fluorodésoxyglucose/tomodensitométrie (18F-FDG TEP/CT) pourrait potentiellement être un outil de stadification précis pour la détection des ganglions lymphatiques métastatiques chez les chiens atteints d'ostéosarcome appendiculaire basé sur la quantification de la valeur standard maximale d'absorption (SUVmax) des ganglions lymphatiques. Les auteurs ont identifié 53 chiens qui furent classifiés avec le 18F-FDG TEP/CT pour l'ostéosarcome appendiculaire primaire. Les patients ont été classés, selon l'état des ganglions lymphatiques, à avoir des ganglions métastatiques ou non métastatiques sur la base d'une analyse cytologique ou histologique. Les valeurs d'absorption standard maximale (SUVmax) du ou des ganglions lymphatiques échantillonnés ont été enregistrées et 3/77 (3,9 %) des ganglions lymphatiques échantillonnés ont été confirmés métastatiques. Un test de Mann-Whitney a révélé une différence statistique du SUVmax des ganglions lymphatiques métastatiques versus non métastatiques [médiane: 6,6 à 95 % intervalle de confiance (IC): 2,56 à 14,37 versus 2,18 IC à 95 %: 2,32 à 3,17, respectivement, valeur de P = 0,05]. Cette analyse rétrospective a révélé une différence significative dans le SUVmax tel que mesuré sur 18F-FDG TEP/CT entre les ganglions lymphatiques métastatiques et les ganglions lymphatiques non métastatiques chez les patients canins atteints d'ostéosarcome appendiculaire, malgré le petit nombre analysé. Bien que ces résultats soient prometteurs, ils doivent être interprétés avec prudence et des études complémentaires sont justifiées.(Traduit par Docteur Serge Messier).

Evaluation of accuracy for 18 F-FDG positron emission tomography and computed tomography for detection of lymph node metastasis in canine oral malignant melanoma.

Tumour stage has been demonstrated to have prognostic significance in canine oral malignant melanoma (OMM). Various evaluation techniques of positron emission tomography/computed tomography (PET/CT) have been reported for staging of head-and-neck tumours in people, but canine-specific data are limited, and reports for CT accuracy have been variable. In this prospective study, the head/neck of client-owned dogs with cytologically or histologically diagnosed OMM were imaged with 18 Fluorine-fluorodeoxyglucose (18 F-FDG) PET/ CT. Bilateral mandibular lymphadenectomy was performed for histopathologic assessment. Two evaluation techniques for CT and PET were applied by four independent observers. CT evaluation utilized both a standardized grading scheme and a subjective clinical interpretation. PET evaluation was first performed solely on 18 F-FDG-uptake in lymph nodes compared to background on a truncated scan excluding the oral cavity. Subsequently, the entire head/neck scan and standardized uptake value (SUV) measurements were available. Receiver operating characteristic analysis was performed with histopathology as gold standard. Twelve dogs completed the study and metastatic OMM was identified in six mandibular lymph nodes from five dogs. Of the CT-interpretation techniques, use of clinical grading performed best (sensitivity = 83% and specificity = 94%). Both PET techniques resulted in 100% sensitivity, but primary tumour site evaluation and use of SUV increased specificity from 78% to 94%. The SUVmax cut-point, 3.3, led to 100% sensitivity and 83% specificity. In this population of dogs, PET appeared to be highly sensitive but at risk of being less specific without use of appropriate parameters and thresholds.

Relative skeletal distribution of proliferating marrow in the adult dog determined using 3'-deoxy-3'-[18 F]fluorothymidine.

3'-deoxy-3'-[18 F]fluorothymidine (18 FLT) is a radiopharmaceutical tracer used with positron emission tomography (PET), often in combination with computed tomography (CT), to image DNA synthesis, and thus, cellular proliferation. Characteristic accumulation of the tracer within haematopoietic bone marrow provides a noninvasive means to assess marrow activity and distribution throughout the living animal. The present study utilizes three-dimensional analysis of 18 FLT-PET/CT scans to quantify the relative skeletal distribution of active marrow by anatomic site in the dog. Scans were performed on six healthy, adult (3-6 years of age), mixed-breed dogs using a commercially available PET/CT scanner consisting of a 64-slice helical CT scanner combined with an integrated four ring, high-resolution LSO PET scanner. Regions of interest encompassing 11 separate skeletal regions (skull, cervical vertebral column, thoracic vertebral column, lumbar vertebral column, sacrum, ribs, sternum, scapulae, proximal humeri, ossa coxarum, and proximal femora) were manually drawn based on CT images and thresholded by standardized uptake value to delineate bone marrow activity. Activity within each skeletal region was then divided by the total skeletal activity to derive the per cent of overall marrow activity within an individual site. The majority of proliferative marrow was located within the vertebral column. Of the sites traditionally accessed clinically for marrow sampling, the proximal humerus contained the largest percentage, followed by the ossa coxarum, proximal femur, and sternum, respectively. This information may be used to guide selection of traditional marrow sampling sites as well as inform efforts to spare important sites of haematopoiesis in radiation therapy planning.

Cerebral 18F-FDG metabolism alteration in a neuropathic pain model following brachial plexus avulsion: A PET/CT study in rats.

The present study aimed to investigate cerebral metabolic changes in a neuropathic pain model following deafferentation. A total of 24 Sprague-Dawley rats were included for modeling of right brachial plexus avulsion (BPA) through the posterior approach. As nerve injury would cause central sensitization and facilitate pain sensitivity in other parts of the body, thermal withdrawal latency (TWL) of the intact forepaw was assessed to investigate the level of pain perception following BPA-induced neuropathic pain. [Fluorine-18]-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET) was applied to the brain before and after brachial plexus avulsion to explore metabolic changes in neuropathic pain following deafferentation. The TWL of the left (intact) forepaw was significantly lower after BPA than that of baseline (p < 0.001). Using TWL as a covariate, standardized uptake values (SUVs) of 18F-FDG significantly increased in the ipsilateral dorsolateral thalamus and contralateral anterodorsal hippocampus after BPA. Conversely, SUVs in multiple brain regions decreased, including the contralateral somatosensory cortex, ipsilateral cingulate cortex, and ipsilateral temporal association cortex. The Pearson correlation analysis showed that the SUVs of the contralateral anterodorsal hippocampus and ipsilateral dorsolateral thalamus were negatively related to the TWL of the intact forepaw, whereas the SUVs in the contralateral somatosensory cortex and ipsilateral cingulate cortex were positively related to it (p < 0.05). These findings indicate that upregulation of metabolism in the anterodorsal hippocampus and dorsolateral thalamus and downregulation metabolism in the contralateral somatosensory cortex and ipsilateral cingulate cortex could be a unique pattern of metabolic changes for neuropathic pain following brachial plexus avulsion.

Prognostic value of fluorine18 flourodeoxyglucose positron emission tomography/computed tomography in dogs with appendicular osteosarcoma.

BACKGROUND: Factors indicative of a negative prognosis for appendicular osteosarcoma (OSA) in dogs are visible metastatic disease, location, and size of lesion. In human medicine maximum standard uptake value (SUVmax ), as measured on a fluorine18 flourodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT), is prognostic for survival for several tumor types. OBJECTIVE: Determine if SUVmax is associated with progression-free interval (PFI) and determination of survival in dogs with appendicular OSA. ANIMALS: Sixty-two dogs with untreated appendicular OSA that had been staged with 18 F-FDG PET/CT. METHODS: Retrospective analysis of the 18 F-FDG PET/CT was performed. Dogs were excluded from the study if they did not receive definitive intent treatment for their primary OSA and adjuvant chemotherapy with carboplatin, or had visible metastatic disease on initial imaging. A region of interest (ROI) was created around the primary tumor to measure SUVmax . Univariable and multivariable Cox proportional hazards analysis was performed to evaluate for associations between variables including SUVmax and outcome of PFI and overall survival (OS). RESULTS: Maximum standard uptake value of the primary tumor was significantly associated with the OS (P = .04) with adjustment for treatment type and monocyte count. The overall median survival time (OST) was 284 days (range, 39-1293 days) with the OST of dogs having an SUVmax of ≥7.4 of 254 days (range, 98-428 days) and dogs with an SUVmax of <7.4 of 680 days (range, 108-811 days, P = .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Maximum standard uptake value as measured via 18 F-FDG PET/CT is significantly associated with survival in dogs with appendicular OSA with a high SUVmax being an indicator of a negative prognosis.

The Use of Ostrich Eggs for In Ovo Research: Making Preclinical Imaging Research Affordable and Available.

In ovo studies are a valuable option in preclinical research, but imaging studies are severely limited by the costs of dedicated equipment needed for small-sized eggs. We sought to verify the feasibility of using larger, ostrich, eggs (Struthio camelus) for imaging on the PET/CT scanners used for routine clinical investigations. Methods: Ostrich eggs were incubated until shortly before hatching, prepared for intravitelline venous injection of contrast medium or radiotracer, and imaged using native CT, contrast-enhanced CT, and PET/CT. Any technical adaptations that were needed to improve the outcome were noted. Results: Of the 34 eggs initially incubated, 12 became fully available for imaging of embryonal development. In ovo imaging with conventional PET/CT not only was feasible but also provided images of good quality, including on dynamic PET imaging. Conclusion: In ovo imaging with ostrich eggs and routine clinical scanners may allow broader application of this field of preclinical research, obviating costly dedicated equipment and reducing the number of animals needed for classic animal research. Further experiments are warranted to refine this novel approach, especially to reduce motion artifacts and improve monitoring of viability.