99mTc-labeled Red Blood Cells Research Articles

RRx-001 Increases Erythrocyte Preferential Adhesion to the Tumor Vasculature.

Red blood cells (RBCs) serve a variety of functions beyond mere oxygen transport both in health and pathology. Notably, RRx-001, a minimally toxic pleiotropic anticancer agent with macrophage activating and vascular normalization properties currently in Phase III trials, induces modification to RBCs which could promote vascular adhesion similar to sickle cells. This study assessed whether RBCs exposed to RRx-001 adhere to the tumor microvasculature and whether this adhesion alters tumor viability. We next investigated the biomechanics of RBC adhesion in the context of local inflammatory cytokines after treatment with RRx-001 as a potential mechanism for preferential tumor aggregation. Human HEP-G2 and HT-29 tumor cells were subcutaneously implanted into nu/nu mice and were infused with RRx-001-treated and Technetium-99m (99mTc)-labeled blood. RBC adhesion was quantified in an in vitro human umbilical vein endothelial cell (HUVEC) assay under both normoxic and hypoxic conditions with administration of either lipopolysaccharide (LPS) or Tumor necrosis alpha (TNF) to mimic the known inflammation in the tumor microenvironment. One hour following administration of 99mTc labeled RBCs treated with 10 mg/kg RRx-001, we observed an approximate 2.0-fold and 1.5-fold increase in 99mTc-labeled RBCs compared to vehicle control in HEPG2 and HT-29 tumor models, respectively. Furthermore, we observed an approximate 40% and 36% decrease in HEP-G2 and HT-29 tumor weight, respectively, following treatment with RRx-001. To quantify RBC adhesive potential, we determined , or the shear stress required for 50% disassociation of RBCs from HUVECs. After administration of TNF-α under normoxia, was determined to be 4.5 dynes/cm2 (95% CI: 4.3–4.7 dynes/cm2) for RBCs treated with 10 M RRx-001, which was significantly different (p < 0.05) from in the absence of treatment. Under hypoxic conditions, the difference of with (4.8 dynes/cm2; 95% CI: 4.6–5.1 dynes/cm2) and without (2.6 dynes/cm2; 95% CI: 2.4–2.8 dynes/cm2) 10 M RRx-001 treatment was exacerbated (p = 0.05). In conclusion, we demonstrated that RBCs treated with RRx-001 preferentially aggregate in HEP-G2 and HT-29 tumors, likely due to interactions between RRx-001 and cysteine residues within RBCs. Furthermore, RRx-001 treated RBCs demonstrated increased adhesive potential to endothelial cells upon introduction of TNF-α and hypoxia suggesting that RRx-001 may induce preferential adhesion in the tumor but not in other tissues with endothelial dysfunction due to conditions prevalent in older cancer patients such as heart disease or diabetic vasculopathy.

Differentiation of insulinoma from accessory spleen by 99mTc-labelled heat-denaturated red blood cell scintigraphy: case report

BackgroundNeuroendocrine tumors (NETs) are rare tumors harboring overexpression of somatostatin receptors (SSTRs) on their cell membrane. Because some organs, such as the spleen, adrenal glands and liver, physiologically express SSTR, it might be challenging to distinguish some pancreatic NETs located in the pancreatic tail from the accessory spleen next to the splenic hilum. In this manuscript, we report a case with hypoglycemia attack and 2 different masses displayed by Gallium 68-tetraazacyclododecane tetraacetic acid-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT).Case presentationA 63-year-old woman presented to the hospital with confusion and profuse sweating. Biochemical diagnosis of insulinoma was established. 68Ga-DOTATATE PET/CT revealed two masses with increased tracer uptake located adjacent to the splenic hilum and inferior pole of the spleen which were initially reported as two separate accessory spleens. Then, 99mTc-labelled heat-denaturated red blood cell (99mTc-HDRBC) scintigraphy-single-photon emission computed tomography (SPECT)/CT was performed to distinguish a NET in the pancreatic tail from accessory spleen at the splenic hilum. Enhanced tracer uptake remained in the inferior pole of spleen, but not in the splenic hilum. The lesions were suggestive of insulinoma in the pancreatic tail and an accessory spleen adjacent to the inferior pole of the spleen.ConclusionApproximately 10% of the population have an accessory spleen which can show similar imaging characteristics with pancreatic NETs, especially if located in the pancreatic tail. In our presented case, 99mTc-HDRBC scintigraphy-SPECT/CT is a useful nuclear medicine method to differentiate a NET in the pancreatic tail from accessory spleen at the splenic hilum which may avoid unnecessary surgeries in the presence of enhanced tracer uptake or vice versa.

Differentiation of Insulinoma from accessory spleen by 99mTc-labelled heat-denaturated red blood cell scintigraphy

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endovascular Treatment of Klippel-Trenaunay Syndrome

Endovascular Treatment of Klippel-Trenaunay Syndrome

Радиометрический контроль утечки химиопрепарата при регионарной перфузии хирургически изолированной конечности

Purpose: Modernization and evaluation of the clinical effectiveness of the technology of continuous radiometric monitoring carried out during high-dose chemotherapy of a surgically isolated limb with tumor foci.&#x0D; Material and methods: A modernized radiometric control technology for regional limb perfusion is proposed. It is based on in vivo labeling of erythrocytes with 99mTc eluate followed by continuous monitoring of the activity of labeled erythrocytes as a simulator of a chemotherapy drug over the heart region. Its distinctive features are intravenous injection of a pyrfotech slice after giving inhalation anesthesia to ensure a sufficient level of red blood cell chelation, as well as using 99mTc activity less than its minimum significant level, which allows working with an open source of ionizing radiation without violating the requirements of radiation safety regulations.&#x0D; Results: The developed technology was successfully used with 106 regional perfusion of the upper and lower extremities in patients with melanoma or sarcoma of soft tissues. In 4 cases, according to the results of radiometric control, the intervention of the surgical team was required to reduce the chemical preparation leakage that was occurring.&#x0D; Conclusion: The technology upgraded by us is characterized by ease of implementation, the ability to take timely measures to prevent or reduce the leakage of a chemotherapy drug from an isolated limb according to the results of continuous in vivo radiometric monitoring of 99mTc-labeled red blood cells over the heart, as well as low radiation load on the patient and staff.

Utilización de hematíes marcados con &lt;sup&gt;99m&lt;/sup&gt;Tc y desnaturalizados por calor en el diagnóstico gammagráfico de un caso infrecuente de esplenosis intratorácica

La esplenosis intratorácica es poco frecuente y se asocia con historia previa de ruptura del bazo y del diafragma causado por un traumatismo. Suele ser asintomática, presentándose como un hallazgo accidental en las imágenes radiográficas o de tomografía computarizada. El diagnóstico definitivo puede realizarse mediante estudios gammagráficos asociados con estudios funcionales de captación de partículas o células. Por su sensibilidad y especificidad, la gammagrafía con hematíes marcados con 99mTc y desnaturalizados por calor es la técnica de referencia que permite confirmar el diagnóstico de esplenosis y diferenciarla de otros procesos que requieren resección quirúrgica Se describe el caso de un varón de 52 años atendido por dolor de tipo pleurítico en hemitórax izquierdo. Las imágenes mostraron derrame pleural izquierdo e infarto pulmonar sin signos de tromboembolismo. Se evidenciaron múltiples focos sugestivos de esplenosis, que fue confirmada mediante gammagrafía esplénica con hematíes marcados con 99mTc y desnaturalizados por calor.

Quantification of intramyocardial blood volume with 99mTc-RBC SPECT-CT imaging: A preclinical study

BackgroundCurrently, there is no established non-invasive imaging approach to directly evaluate myocardial microcirculatory function in order to diagnose microvascular disease independent of co-existing epicardial disease. In this work, we developed a methodological framework for quantification of intramyocardial blood volume (IMBV) as a novel index of microcirculatory function with SPECT/CT imaging of 99mTc-labeled red blood cells (RBCs). MethodsDual-gated myocardial SPECT/CT equilibrium imaging of 99mTc-RBCs was performed on twelve canines under resting conditions. Five correction schemes were studied: cardiac gating with no other corrections (CG), CG with attenuation correction (CG + AC), CG + AC with scatter correction (CG + AC + SC), dual cardiorespiratory gating with AC + SC (DG + AC + SC), and DG + AC + SC with partial volume correction (DG + AC + SC + PVC). Quantification of IMBV using each approach was evaluated in comparison to those obtained from all corrections. The in vivo SPECT estimates of IMBV values were validated against those obtained from ex vivo microCT imaging of the casted hearts. ResultsThe estimated IMBV with all corrections was 0.15 ± 0.03 for the end-diastolic phase and 0.11 ± 0.03 for the end-systolic phase. The cycle-dependent change in IMBV (ΔIMBV) with all corrections was 23.9 ± 8.6%. Schemes that applied no correction or partial correction resulted in significant over-estimation of IMBV and significant under-underestimation of ΔIMBV. Estimates of IMBV and ΔIMBV using all corrections were consistent with values reported in the literature using invasive techniques. In vivo SPECT estimates of IMBV strongly correlated (R2 ≥ 0.70) with ex vivo measures for the various correction schemes, while the fully corrected scheme yielded the smallest bias. ConclusionsNon-invasive quantification of IMBV is feasible using 99mTc-RBCs SPECT/CT imaging, however, requires full compensation of physical degradation factors.

Intérêt de l’exploration de l’intestin grêle dans les hémorragies digestives

In France, upper gastrointestinal haemorrhages have an estimated annual incidence of 143cases per 100,000inhabitants. Classically, two types of digestive hemorrhage are described: acute and chronic digestive hemorrhages. Upper endoscopy is carried out in case of hematemesis or melena. It requires that the patient has been fasting for at least 6hours for solids and 3hours for liquids. The main etiologies of hemorrhagic hemorrhage of the origin are the vascular abnormalities, inflammatory or drug-induced ulcerations, intestinal tumors, Meckel's diverticulum, and Dieulafoy ulcer. The modalities of exploration of the small intestine before digestive hemorrhage are the wireless capsule, a reference examination for the exploration of the small intestine, enteroscopy, therapeutic examination, entero-CT or MRI, and 99mTc-labeled red blood cell scintigraphy. In this review, we will discuss the different etiologies of the digestive haemorrhage of intestinal origin and propose a management algorithm.

Preclinical evaluation of heat-denatured [18F]FDG-labeled red blood cells for detecting splenic tissues with PET in rats

IntroductionHeat-denatured 99mTc-labeled red blood cells (RBCs) are used for detecting splenic tissues with scintigraphy. The present study aimed to evaluate the feasibility of using heat-denatured [18F]fluorodeoxyglucose ([18F]FDG)-labeled RBCs in detecting splenic tissues using positron emission tomography (PET) in rats. MethodsRBCs were washed with phosphate buffered saline, labeled with [18F]FDG at 38°C, and heat-denatured at 50°C for 15 min. In vitro stability was assessed by measuring extracellular radioactivity during the 0–180 min incubation at 37°C. Thin layer chromatography (TLC) of the extracellular fluid was performed. The autologous RBCs were intravenously injected in four rats and PET scanning was simultaneously performed for 30 min. Time-activity curves of several organs, including the spleen, were analyzed on the PET images. ResultsLabeling efficiency was 92%. Low levels of radioactivity were released from the labeled RBCs for 180 min. TLC revealed that 80% of the released radioactivity was due to [18F]FDG-6-phosphate. Whole body images showed strong uptake of heat-denatured [18F]FDG-labeled RBCs in the spleen soon after injection in all four rats. Time-activity curves revealed that the splenic uptake continued to increase for 30 min and the amount of radioactivity in the other organs, except the urinary bladder, decreased after the initial surge. ConclusionsHeat-denatured [18F]FDG-labeled RBCs are suitable spleen-specific agents for PET. This method is clinically relevant as an alternative for heat-denatured 99mTc-labeled RBC scintigraphy.

Fully automatic multi-atlas segmentation of CTA for partial volume correction in cardiac SPECT/CT

Anatomical-based partial volume correction (PVC) has been shown to improve image quality and quantitative accuracy in cardiac SPECT/CT. However, this method requires manual segmentation of various organs from contrast-enhanced computed tomography angiography (CTA) data. In order to achieve fully automatic CTA segmentation for clinical translation, we investigated the most common multi-atlas segmentation methods. We also modified the multi-atlas segmentation method by introducing a novel label fusion algorithm for multiple organ segmentation to eliminate overlap and gap voxels. To evaluate our proposed automatic segmentation, eight canine 99mTc-labeled red blood cell SPECT/CT datasets that incorporated PVC were analyzed, using the leave-one-out approach. The Dice similarity coefficient of each organ was computed. Compared to the conventional label fusion method, our proposed label fusion method effectively eliminated gaps and overlaps and improved the CTA segmentation accuracy. The anatomical-based PVC of cardiac SPECT images with automatic multi-atlas segmentation provided consistent image quality and quantitative estimation of intramyocardial blood volume, as compared to those derived using manual segmentation. In conclusion, our proposed automatic multi-atlas segmentation method of CTAs is feasible, practical, and facilitates anatomical-based PVC of cardiac SPECT/CT images.

Excretion of radionuclides in human breast milk after nuclear medicine examinations. Biokinetic and dosimetric data and recommendations on breastfeeding interruption.

To review early recommendations and propose guidelines for breastfeeding interruption after administration of radiopharmaceuticals, based on additional biokinetic and dosimetric data. Activity concentrations in breast milk from 53 breastfeeding patients were determined. The milk was collected at various times after administration of 16 different radiopharmaceuticals. The fraction of the activity administered to the mother excreted in the breast milk, the absorbed doses to various organs and tissues and the effective dose to the infant were estimated. The fraction of the administered activity excreted per millilitre of milk varied widely from 10(-10) to 10(-3) MBq/MBq administered. For (99m)Tc-labelled radiopharmaceuticals, the total fraction of the administered activity excreted in the milk varied from 0.0057 % for (99m)Tc-labelled red blood cells (RBC) to 19 % for (99m)Tc-pertechnetate. The effective dose to an infant per unit activity administered to the mother ranged from 6.7 × 10(-6) mSv/MBq for (99m)Tc-labelled RBC to 3.6 × 10(-2) mSv/MBq for (99m)Tc-pertechnetate. For the other radiopharmaceuticals, the total fraction of administered activity excreted in the milk varied from 0.018 % ((51)Cr-EDTA) to 48 % ((131)I-NaI). The effective dose ranged from 5.6 × 10(-5) mSvinfant/MBqmother ((51)Cr-EDTA) to 106 mSvinfant/MBqmother ((131)I-NaI). Based on an effective dose limit of 1 mSv to the infant and a typical administered activity, we recommend cessation of breastfeeding for (131)I-NaI and interruption of feeding for 12 h for (125)I-iodohippurate, (131)I-iodohippurate, (99m)Tc-pertechnetate and (99m)Tc-MAA. During this 12-h period all breast milk should be expressed at least three times and discarded. For the other radiopharmaceuticals included in this study, no interruption of breastfeeding is necessary.

Inferior Vena Cava Filter Thrombus: a Possible Cause of an Unanticipated Finding of (99m)Tc-labeled Red Blood Cell Scintigraphy.

(99m)Tc-labeled red blood cell scintigraphy, a sensitive and specific diagnostic test, is useful for patients suspected of suffering from active gastrointestinal bleeding. This study follows a case of a patient who was suspected of gastrointestinal bleeding after an inferior vena cava filter was inserted due to a deep vein thrombosis of the femoral vein. To evaluate an exact focus of bleeding, (99m)Tc-labeled red blood cell scintigraphy was executed. Herein, an unanticipated finding of (99m)Tc-labeled red blood cell scintigraphy probably due to a thrombus on the inferior vena cava filter is reported.

Vascular Physiology and Protein Disposition in a Preclinical Model of Neurodegeneration

The development of clinically relevant preclinical models that mimic the hallmarks of neurodegenerative disease is an ongoing pursuit in early drug development. In particular, robust physiological characterization of central nervous system (CNS) disease models is necessary to predict drug delivery to target tissues and to correctly interpret pharmacodynamic responses to disease-modifying therapeutic candidates. Efficient drug delivery across the blood-CNS barrier is a particularly daunting task, prompting our strategy to evaluate the biodistribution of five distinct molecular probes in a well-characterized mouse model of neurodegeneration. A transgenic mouse model of amyotrophic lateral sclerosis was selected based on a phenotype resembling clinical symptoms, including loss of motor neurons from the spinal cord and paralysis in one or more limbs, due to expression of a G93A mutant form of human superoxide dismutase (SOD1). The tissue distributions of two proteins, albumin and a representative immunoglobulin G antibody, as well as two blood flow markers, the lipophilic blood flow marker Ceretec (i.e., (99m)Tc-HMPAO) and the polar ionic tracer, rubidium-86 chloride ((86)RbCl), were measured following intravenous injection in SOD1(G93A) and age-matched control mice. The radiopharmaceutical TechneScan PYP was also used to measure the distribution of (99m)Tc-labeled red blood cells as a blood pool marker. Both the antibody and (86)Rb were able to cross the blood-spinal cord barrier in SOD1(G93A) mice to a greater extent than in control mice. Although the biodistribution patterns of antibody, albumin, and RBCs were largely similar, notable differences were detected in muscle and skin. Moreover, vastly different biodistribution patterns were observed for a lipophilic and polar perfusion agent, with SOD1(G93A) mutation resulting in reduced renal filtration rates for the former but not the latter. Overall, the multiprobe strategy provided an opportunity to efficiently collect an abundance of physiological information, including the degree and regional extent of blood-CNS barrier permeability, in a preclinical model of neurodegeneration.

Watch and wait: Conservative management of lower gastrointestinal bleeding

BackgroundAlthough indications for surgery in lower gastrointestinal bleeding (LGIB) are widely described, practice varies. This study was designed to assess outcomes of patients allowed to exceed traditional triggers for surgery because of LGIB. MethodsThis is a retrospective review of patients at an urban tertiary hospital over a 3-y period that had LGIB necessitating 99mTc-labeled red blood cell scintigraphy. Traditional indications for operative treatment of LGIB were defined as transfusion of >6U of packed red blood cells, hemodynamic instability, bleeding lasting >72h, and rebleeding after cessation of bleeding for >24h. ResultsOne hundred ninety-four LGIB patients had scintigraphy during the period of study with 180 meeting inclusion criteria. Fifty-six (31%) patients had at least one operative indication, and 32 (60%) were managed nonoperatively without a mortality. There were two (8.3%) mortalities in those who had operative management, one of which was because of exsanguination. Eighteen (32%) patients who met operative criteria were unlocalized. ConclusionsPatients with LGIB can be safely managed nonoperatively, even when the bleed is unlocalized and traditional indications for surgery are met. Exsanguinations because of LGIB treated nonoperatively are rare except in patients deemed not to be surgical candidates.

Blue rubber bleb nevus syndrome: hybrid spect-CT with 99mtc-labelled rbc and its added value over planar scintigraphy

Blue rubber bleb nevus syndrome (BRBNS) is a rare clinical entity characterized by multiple venous malformations (hemangiomas) of the skin and gastrointestinal tract. These hemangiomas usually cause episodes of occult gastrointestinal bleeding leading to iron deficiency anemia, and also carry a significant potential for serious hemorrhage. The 99mechnetium (99mTc)-labeled red blood cell scintigraphy has traditionally been utilized in the localization of occult bleeding sites in patients with suspected vascular malformations, angiodysplasia, and Meckel’s diverticulum. We report the incremental value of 99mTc-labeled red blood cell hybrid single-photon emission computed tomography-computed tomography (SPECT-CT) over planar scintigraphy alone in a 12-year-old female patient with BRBNS.

Abdominal splenosis: An often underdiagnosed entity

Splenosis is defined as the heterotopic autotransplantation of splenic tissue because of a ruptured spleen due to trauma or surgery. It is a benign and incidental finding, although imaging tests may sometimes orient toward malignancy simulating renal tumors, abdominal lymphomas, endometriosis, among other. We report the case of a 42-year old male in whom a MRI was performed after a study due to abdominal pain. Multiple enlarged lymph nodes were observed in the abdomen, suggestive of lymphoproliferative disease. As an important background, splenectomy was carried out due to abdominal trauma at age 9. After several studies, it was decided to perform a 99mTc-labeled heat-damaged red blood cell scintigraphy that showed multiple pathological deposits distributed throughout the abdomen, and even the pelvis, being consistent with splenosis.

Real-time systemic leakage monitoring with 99mTc-labelled red blood cells during hyperthermic isolated limb and lung perfusion with melphalan and tumour necrosis factor-a

Real-time systemic leakage monitoring with 99mTc-labelled red blood cells during hyperthermic isolated limb and lung perfusion with melphalan and tumour necrosis factor-a

Huge Varicose Inferior Mesenteric Vein: an Unanticipated (99m) Tc-labeled Red Blood Cell Scintigraphy Finding.

Ectopic varices (EcV) are enlarged portosystemic venous collaterals, which usually develop secondary to portal hypertension (PHT). Mesocaval collateral vessels are unusual pathways to decompress the portal system. Here we report the case of a huge varicose inferior mesenteric vein (IMV) that drained into perirectal collateral veins, demonstrated by (99m)Tc-labeled red blood cell (RBC) scintigraphy performed for lower gastrointestinal (GI) bleeding in a 14-year-old girl. This case illustrates the crucial role of (99m)Tc-labeled RBC scintigraphy for the diagnosis of rare ectopic lower GI varices.

Esplenosis abdominal: una entidad frecuentemente infradiagnosticada

Splenosis is defined as the heterotopic autotransplantation of splenic tissue because of a ruptured spleen due to trauma or surgery. It is a benign and incidental finding, although imaging tests may sometimes orient toward malignancy simulating renal tumors, abdominal lymphomas, endometriosis, among other. We report the case of a 42-year old male in whom a MRI was performed after a study due to abdominal pain. Multiple enlarged lymph nodes were observed in the abdomen, suggestive of lymphoproliferative disease. As an important background, splenectomy was carried out due to abdominal trauma at age 9. After several studies, it was decided to perform a 99mTc-labeled heat-damaged red blood cell scintigraphy that showed multiple pathological deposits distributed throughout the abdomen, and even the pelvis, being consistent with splenosis.

Roles of myocardial blood volume and flow in coronary artery disease: an experimental MRI study at rest and during hyperemia

To validate fast perfusion mapping techniques in a setting of coronary artery stenosis, and to further assess the relationship of absolute myocardial blood volume (MBV) and blood flow (MBF) to global myocardial oxygen demand. A group of 27 mongrel dogs were divided into 10 controls and 17 with acute coronary stenosis. On 1.5-T MRI, first-pass perfusion imaging with a bolus injection of a blood-pool contrast agent was performed to determine myocardial perfusion both at rest and during either dipyridamole-induced vasodilation or dobutamine-induced stress. Regional values of MBF and MBV were quantified by using a fast mapping technique. Color microspheres and (99m)Tc-labeled red blood cells were injected to obtain respective gold standards. Microsphere-measured MBF and (99m)Tc-measured MBV reference values correlated well with the MR results. Given the same changes in MBF, changes in MBV are twofold greater with dobutamine than with dipyridamole. Under dobutamine stress, MBV shows better association with total myocardial oxygen demand than MBF. Coronary stenosis progressively reduced this association in the presence of increased stenosis severity. MR first-pass perfusion can rapidly estimate regional MBF and MBV. Absolute quantification of MBV may add additional information on stenosis severity and myocardial viability compared with standard qualitative clinical evaluations of myocardial perfusion.