Outcomes Following a False-Positive Multi-Cancer Early Detection Test: Results from DETECT-A, the First Large, Prospective, Interventional MCED Study.

Guideline recommended standard of care screening is available for four cancer types; most cancer-related deaths are caused by cancers without standard of care screening. DETECT-A is the first prospective interventional trial evaluating a multi-cancer early detection (MCED) blood test (CancerSEEK) in women without a history of cancer, providing the first opportunity to assess the long-term outcomes of individuals with false-positive (FP) MCED results. This prospective analysis of DETECT-A participants with FP results evaluates the performance of an imaging-based diagnostic workflow and examines cancer risk following a FP result. This analysis included all DETECT-A participants with a positive CancerSEEK test and subsequent flourine-18 fluorodeoxyglucose positron emission tomography-IV contrast-enhanced computed tomography (18-F-FDG PET-CT) imaging and clinical workup indicating no evidence of cancer within 1 year of enrollment (n = 98). Medical records, study interactions, and study surveys were used to assess cancer incidence, treatments, and clinical outcomes through August 2023. Ninety-five of 98 participants with a FP result remained cancer-free with a median follow-up of 3.6 years (IQR: 2.5-4.1) from determination of FP status. Three incident cancers were observed over the follow-up period. One bilateral stage IIIC ovarian cancer was diagnosed 1.9 years after determination of FP status; two stage I breast cancers were diagnosed 0.1 and 1.6 years from determination of FP status. The annual incidence rate of cancer during follow-up from FP determination was 1.0% (95% confidence interval, 0.2%-2.8%). Participants with a positive CancerSEEK test who underwent 18-F-FDG PET-CT and clinical workup without cancer findings had low risk for cancer over the following several years. Prevention Relevance: This study provides multiyear clinical outcomes data following a false-positive multi-cancer early detection test for individuals participating in a prospective interventional trial. It provides a preliminary performance assessment of an imaging-based diagnostic workflow following a false-positive multi-cancer early detection test.

Multi-year clinical outcomes of cancers diagnosed following detection by a blood-based multi-cancer early detection (MCED) test.

In the U.S., <20% of cancers are diagnosed by standard-of-care (SoC) screening. Multi-cancer early detection (MCED) tests offer the opportunity to expand cancer screening. Understanding the characteristics and clinical outcomes of MCED-detected cancers is critical to clarifying MCED tests' potential impact. DETECT-A is the first prospective interventional trial of an MCED blood test (CancerSEEK). CancerSEEK, coupled with diagnostic PET-CT, identified cancers including those not detected by SoC screening, the majority of which were localized or regional. We report multi-year outcomes in patients with cancers diagnosed following a positive CancerSEEK test. Nine cancer types were diagnosed in 26 participants whose cancers were first detected by CancerSEEK. Information on cancer diagnoses, treatments, and clinical outcomes was extracted from medical records through November 2022. Data collection occurred a median of 4.4 years (IQR: 4.1-4.6) following study enrollment. Thirteen of 26 (50%) participants were alive and cancer-free [ovarian (4), thyroid (1), uterine (2), breast (1), colorectal (2), and lung (3)]; 7/13 (54%) had cancers without recommended SoC screening modalities. All 8 treated stage I or II participants (8/8, 100%) and 12/14 (86%) surgically-treated participants were alive and cancer-free. Eligibility for surgical treatment was associated with favorable multi-year outcomes (p = 0.0002). Half of participants with MCED-detected cancers were alive and cancer-free after 4.4 years median follow-up. Most were diagnosed with early-stage cancers and were treated surgically. These results suggest that early cancer detection by CancerSEEK may have facilitated curative-intent treatments and associated positive clinical outcomes in some DETECT-A participants.

Outcomes following a false positive multi-cancer early detection (MCED) test: Results from DETECT-A, the first large, prospective, interventional MCED study.

Guideline recommended standard of care (SoC) screening is available for four cancer types; most cancer-related deaths are caused by cancers without SoC screening. DETECT-A is the first prospective interventional trial evaluating an MCED blood test (CancerSEEK) in women without a history of cancer, providing the first opportunity to assess the long-term outcomes of individuals with false positive (FP) MCED results. This prospective analysis of DETECT-A participants with FP results evaluates the performance of an imaging-based diagnostic workflow and examines cancer risk following a FP result. This analysis included all DETECT-A participants with a positive CancerSEEK test and subsequent flourine-18 fluorodeoxyglucose positron emission tomography-IV contrast enhanced computed tomography (18-F-FDG PET-CT) imaging and clinical workup indicating no evidence of cancer within one year of enrollment (n=98). Medical records, study interactions, and study surveys were used to assess cancer incidence, treatments, and clinical outcomes through August 2023. Ninety-five of 98 participants with a FP result remained cancer-free with a median follow-up of 3.6 years (IQR: 2.5-4.1) from determination of FP status. Three incident cancers were observed over the follow-up period. One bilateral stage IIIC ovarian cancer was diagnosed 1.9 years after determination of FP status; two stage I breast cancers were diagnosed 0.1 and 1.6 years from determination of FP status. The annual incidence rate of cancer during follow-up from FP determination was 1.0% (95% CI: 0.2%-2.8%). Participants with a positive CancerSEEK test who underwent 18-F-FDG PET-CT and clinical workup without cancer findings had low risk for cancer over the following several years.

Multimodal analysis of granulocytes, monocytes, and platelets in patients with cystic fibrosis before and after Elexacaftor-Tezacaftor-Ivacaftor treatment.

Cystic fibrosis (CF) is a monogenetic disease caused by an impairment of the cystic fibrosis transmembrane conductance regulator (CFTR). CF affects multiple organs and is associated with acute and chronic inflammation. In 2020, Elexacaftor-Tezacaftor-Ivacaftor (ETI) was approved to enhance and restore the remaining CFTR functionality. This study investigates cellular innate immunity, with a focus on neutrophil activation and phenotype, comparing healthy volunteers with patients with CF before (T1, n = 13) and after six months (T2, n = 11) of ETI treatment. ETI treatment reduced sweat chloride (T1: 95 mmol/l (83|108) vs. T2: 32 mmol/l (25|62), p < 0.01, median, first|third quartile) and significantly improved pulmonal function (FEV1 T1: 2.66 l (1.92|3.04) vs. T2: 3.69 l (3.00|4.03), p < 0.01). Moreover, there was a significant decrease in the biomarker human epididymis protein 4 (T1: 6.2 ng/ml (4.6|6.3) vs. T2: 3.0 ng/ml (2.2|3.7), p < 0.01) and a small but significant decrease in matrix metallopeptidase 9 (T1: 45.5 ng/ml (32.5|140.1) vs. T2: 28.2 ng/ml (18.2|33.6), p < 0.05). Neutrophil phenotype (CD10, CD11b, CD62L, and CD66b) and function (radical oxygen species generation, chemotactic and phagocytic activity) remained largely unaffected by ETI treatment. Likewise, monocyte phenotype and markers of platelet activation were similar at T1 and T2. In summary, the present study confirmed a positive impact on patients with CF after ETI treatment. However, neither beneficial nor harmful effects of ETI treatment on cellular innate immunity could be detected, possibly due to the study population consisting of patients with well-controlled CF.

Modulation of Neutrophil Activity by Soluble Complement Cleavage Products-An In-Depth Analysis.

The cellular and fluid phase-innate immune responses of many diseases predominantly involve activated neutrophil granulocytes and complement factors. However, a comparative systematic analysis of the early impact of key soluble complement cleavage products, including anaphylatoxins, on neutrophil granulocyte function is lacking. Neutrophil activity was monitored by flow cytometry regarding cellular (electro-)physiology, cellular activity, and changes in the surface expression of activation markers. The study revealed no major effects induced by C3a or C4a on neutrophil functions. By contrast, exposure to C5a or C5a des-Arg stimulated neutrophil activity as reflected in changes in membrane potential, intracellular pH, glucose uptake, and cellular size. Similarly, C5a and C5a des-Arg but no other monitored complement cleavage product enhanced phagocytosis and reactive oxygen species generation. C5a and C5a des-Arg also altered the neutrophil surface expression of several complement receptors and neutrophil activation markers, including C5aR1, CD62L, CD10, and CD11b, among others. In addition, a detailed characterization of the C5a-induced effects was performed with a time resolution of seconds. The multiparametric response of neutrophils was further analyzed by a principal component analysis, revealing CD11b, CD10, and CD16 to be key surrogates of the C5a-induced effects. Overall, we provide a comprehensive insight into the very early interactions of neutrophil granulocytes with activated complement split products and the resulting neutrophil activity. The results provide a basis for a better and, importantly, time-resolved and multiparametric understanding of neutrophil-related (patho-)physiologies.

Simultaneous Measurement of Changes in Neutrophil Granulocyte Membrane Potential, Intracellular pH, and Cell Size by Multiparametric Flow Cytometry.

Neutrophils provide rapid and efficient defense mechanisms against invading pathogens. Upon stimulation with proinflammatory mediators, including complement factors and bacterial peptides, neutrophils respond with changes in their membrane potential, intracellular pH, and cellular size. This study provides an approach to quantify these important changes simultaneously using multiparametric flow cytometry, thereby revealing a typical sequence of neutrophil activation consisting of depolarization, alkalization, and increase in cellular size. Additionally, the time resolution of the flow cytometric measurement is improved in order to allow changes that occur within seconds to be monitored, and thus to enhance the kinetic analysis of the neutrophil response. The method is appropriate for the reliable semiquantitative detection of small variations with respect to an increase, no change, and decrease in those parameters as demonstrated by the screening of various proinflammatory mediators. As a translational outlook, the findings are put into context in inflammatory conditions in vitro as well as in a clinically relevant whole blood model of endotoxemia. Taken together, the multiparametric analysis of neutrophil responsiveness regarding depolarization, alkalization, and changes in cellular size may contribute to a better understanding of neutrophils in health and disease, thus potentially yielding innovative mechanistic insights and possible novel diagnostic and/or prognostic approaches.

Activation of Neutrophil Granulocytes by Platelet-Activating Factor Is Impaired During Experimental Sepsis.

Platelet-activating factor (PAF) is an important mediator of the systemic inflammatory response. In the case of sepsis, proper activation and function of neutrophils as the first line of cellular defense are based on a well-balanced physiological response. However, little is known about the role of PAF in cellular changes of neutrophils during sepsis. Therefore, this study investigates the reaction patterns of neutrophils induced by PAF with a focus on membrane potential (MP), intracellular pH, and cellular swelling under physiological and pathophysiological conditions and hypothesizes that the PAF-mediated response of granulocytes is altered during sepsis. The cellular response of granulocytes including MP, intracellular pH, cellular swelling, and other activation markers were analyzed by multiparametric flow cytometry. In addition, the chemotactic activity and the formation of platelet-neutrophil complexes after exposure to PAF were investigated. The changes of the (electro-)physiological response features were translationally verified in a human ex vivo whole blood model of endotoxemia as well as during polymicrobial porcine sepsis. In neutrophils from healthy human donors, PAF elicited a rapid depolarization, an intracellular alkalization, and an increase in cell size in a time- and dose-dependent manner. Mechanistically, the alkalization was dependent on sodium-proton exchanger 1 (NHE1) activity, while the change in cellular shape was sodium flux- but only partially NHE1-dependent. In a pathophysiological altered environment, the PAF-induced response of neutrophils was modulated. Acidifying the extracellular pH in vitro enhanced PAF-mediated depolarization, whereas the increases in cell size and intracellular pH were largely unaffected. Ex vivo exposure of human whole blood to lipopolysaccharide diminished the PAF-induced intracellular alkalization and the change in neutrophil size. During experimental porcine sepsis, depolarization of the MP was significantly impaired. Additionally, there was a trend for increased cellular swelling, whereas intracellular alkalization remained stable. Overall, an impaired (electro-)physiological response of neutrophils to PAF stimulation represents a cellular hallmark of those cells challenged during systemic inflammation. Furthermore, this altered response may be indicative of and causative for the development of neutrophil dysfunction during sepsis.

Interleukin 8 Elicits Rapid Physiological Changes in Neutrophils That Are Altered by Inflammatory Conditions.

A sufficient response of neutrophil granulocytes stimulated by interleukin (IL)-8 is vital during systemic inflammation, for example, in sepsis or severe trauma. Moreover, IL-8 is clinically used as biomarker of inflammatory processes. However, the effects of IL-8 on cellular key regulators of neutrophil properties such as the intracellular pH (pHi) in dependence of ion transport proteins and during inflammation remain to be elucidated. Therefore, we investigated in detail the fundamental changes in pHi, cellular shape, and chemotactic activity elicited by IL-8. Using flow cytometric methods, we determined that the IL-8-induced cellular activity was largely dependent on specific ion channels and transporters, such as the sodium-proton exchanger 1 (NHE1) and non-NHE1-dependent sodium flux. Exposing neutrophils in vitro to a proinflammatory micromilieu with N-formyl-Met-Leu-Phe, LPS, or IL-8 resulted in a diminished response regarding the increase in cellular size and pH. The detailed kinetics of the reduced reactivity of the neutrophil granulocytes could be illustrated in a near-real-time flow cytometric measurement. Last, the LPS-mediated impairment of the IL-8-induced response in neutrophils was confirmed in a translational, animal-free human whole blood model. Overall, we provide novel mechanistic insights for the interaction of IL-8 with neutrophil granulocytes and report in detail about its alteration during systemic inflammation.

Animal-Free Human Whole Blood Sepsis Model to Study Changes in Innate Immunity.

Studying innate immunity in humans is crucial for understanding its role in the pathophysiology of systemic inflammation, particularly in the complex setting of sepsis. Therefore, we standardized a step-by-step process from the venipuncture to the transfer in a human model system, while closely monitoring the inflammatory response for up to three hours. We designed an animal-free, human whole blood sepsis model using a commercially available, simple to use, tubing system. First, we analyzed routine clinical parameters, including cell count and blood gas analysis. Second, we demonstrated that extracellular activation markers (e.g., CD11b and CD62l) as well as intracellular metabolic (intracellular pH) and functional (generation of radical oxygen species) features remained stable after incubation in the whole blood model. Third, we mimicked systemic inflammation during early sepsis by exposure of whole blood to pathogen-associated molecular patterns. Stimulation with lipopolysaccharide revealed the capability of the model system to evoke a sepsis-like inflammatory phenotype of innate immunity. In summary, the presented model serves as a convenient, economic, and reliable platform to study innate immunity in human whole blood, which may yield clinically important insights.

Early Questing by Lone Star Tick Larvae, New York and Massachusetts, USA, 2018.

Subtropical lone star tick larvae typically emerge in late summer. We found clusters of host-seeking lone star tick larvae during early June 2018 in New York and Massachusetts, USA. Invasion and persistence of this tick in more northern locations may have been promoted by adaptation to an accelerated life cycle.

Probing 3D Collective Cancer Invasion Using Double-Stranded Locked Nucleic Acid Biosensors.

Cancer is a leading cause of death worldwide and metastases are responsible for over 90% of human cancer deaths. There is an urgent need to develop novel therapeutics for suppressing cancer invasion, the initial step of metastasis. Nevertheless, the regulation of cancer invasion is poorly understood due to a paucity of tools for monitoring the invasion process in 3D microenvironments. Here, we report a double-stranded locked nucleic acid (dsLNA) biosensor for investigating 3D collective cancer invasion. By incorporating multiphoton microscopy and the dsLNA biosensor, we perform dynamic single cell gene expression analysis while simultaneously characterizing the biomechanical interaction between the invading sprouts and the extracellular matrix. Gene profiling of invasive leader cells and detached cells suggest distinctive signaling mechanisms involved in collective and individual invasion in the 3D microenvironment. Our results underscore the involvement of Notch signaling in 3D collective cancer invasion, which warrants further investigation toward antimetastasis therapy in the future.

A functionalized, injectable hydrogel for localized drug delivery with tunable thermosensitivity: synthesis and characterization of physical and toxicological properties.

Thermosensitive injectable hydrogels have been used for the delivery of pharmacological and cellular therapies in a variety of soft tissue applications. A promising class of synthetic, injectable hydrogels based upon oligo(ethylene glycol) methacrylate (OEGMA) monomers has been previously reported, but these polymers lack reactive groups for covalent attachment of therapeutic molecules. In this work, thermosensitive, amine-reactive and amine-functionalized polymers were developed by incorporation of methacrylic acid N-hydroxysuccinimide ester or 2-aminoethyl methacrylate into OEGMA-based polymers. A model therapeutic peptide, bivalirudin, was conjugated to the amine-reactive hydrogel to investigate effects on the polymer thermosensitivity and gelation properties. The ability to tune the thermosensitivity of the polymer in order to compensate for peptide hydrophilicity and maintain gelation capability below physiological temperature was demonstrated. Cell encapsulation studies using an H9 T-cell line (CD4+) were conducted to evaluate feasibility of the hydrogel as a carrier for cellular therapies. Although this class of polymers is generally considered to be non-toxic, it was found that concentrations required for gelation were incompatible with cell survival. Investigation into the cause of cytotoxicity revealed that a hydrolysis byproduct, diethylene glycol monomethyl ether, is likely a contributing factor. While modifications to structure or composition will be required to enable viable cell encapsulation, the functionalized injectable hydrogel has the potential for controlled delivery of a wide range of drugs.

Treatment of penetrating brain injury in a rat model using collagen scaffolds incorporating soluble Nogo receptor.

Injuries and diseases of the central nervous system (CNS) have the potential to cause permanent loss of brain parenchyma, with severe neurological consequences. Cavitary defects in the brain may afford the possibility of treatment with biomaterials that fill the lesion site while delivering therapeutic agents. This study examined the treatment of penetrating brain injury (PBI) in a rat model with collagen biomaterials and a soluble Nogo receptor (sNgR) molecule. sNgR was aimed at neutralizing myelin proteins that hinder axon regeneration by inducing growth cone collapse. Scaffolds containing sNgR were implanted in the brains of adult rats 1 week after injury and analysed 4 weeks or 8 weeks later. Histological analysis revealed that the scaffolds filled the lesion sites, remained intact with open pores and were infiltrated with cells and extracellular matrix. Immunohistochemical staining demonstrated the composition of the cellular infiltrate to include macrophages, astrocytes and vascular endothelial cells. Isolated regions of the scaffold borders showed integration with surrounding viable brain tissue that included neurons and oligodendrocytes. While axon regeneration was not detected in the scaffolds, the cellular infiltration and vascularization of the lesion site demonstrated a modification of the injury environment with implications for regenerative strategies.

Viscoelastic characterization of rat cerebral cortex and type I collagen scaffolds for central nervous system tissue engineering.

In the field of tissue engineering and regenerative medicine for the central nervous system, therapeutic strategies may involve implantation of biomaterial scaffolds into the brain. An understanding of the relationship between the brain and the scaffold mechanical properties can help in the selection of a safe and effective biomaterial. This research demonstrates the use of indentation testing along with viscoelastic modeling to characterize and compare mechanical properties of in situ rat cerebral cortex and collagen scaffolds of varying collagen concentration. The stress-relaxation solution for indentation of a viscoelastic material was derived based on a five-element Maxwell model and use of the correspondence principle. Applying the model to experimental stress-relaxation data, the brain was characterized by three shear moduli G(1)=1.6±0.10 kPa, G(2)=2.0±0.15 kPa, G(3)=1.8±0.20 kPa, and two viscosities η(2)=11.0 ± 0.44 kPa⋅s, η(3)=148.7 ± 6.70 kPa⋅s, with corresponding relaxation time constants τ(1)=5.7±0.3 s and τ(2)=88.4 ± 7.6 s. The brain showed average relaxation of 74% from its peak force during loading to an approximately asymptotic force over a 5 minute hold at constant displacement. Collagen scaffolds generally showed increasing trends in the shear moduli, viscosities, and percentage relaxation with increasing collagen concentration. While the brain had similar stiffness to the 1.0% collagen scaffold during the loading phase, the brain's relaxation behavior was distinct from all of the scaffolds. Similarities and differences between the mechanical behavior of the brain and collagen scaffolds of varying collagen concentration are discussed in relation to application of biomaterials for regenerative medicine.

Implantation of a collagen scaffold seeded with adult rat hippocampal progenitors in a rat model of penetrating brain injury.

Penetrating brain injury (PBI) is a complex central nervous system injury in which mechanical damage to brain parenchyma results in hemorrhage, ischemia, broad areas of necrosis, and eventually cavitation. The permanent loss of brain tissue affords the possibility of treatment using a biomaterial scaffold to fill the lesion site and potentially deliver pharmacological or cellular therapeutic agents. The administration of cellular therapy may be of benefit in both mitigating the secondary injury process and promoting regeneration through replacement of certain cell populations. This study investigated the survival and differentiation of adult rat hippocampal neural progenitor cells delivered by a collagen scaffold in a rat model of PBI. The cell-scaffold construct was implanted 1 week after injury and was observed to remain intact with open pores upon analysis 4 weeks later. Implanted neural progenitors were found to have survived within the scaffold, and also to have migrated into the surrounding brain. Differentiated phenotypes included astrocytes, oligodendrocytes, vascular endothelial cells, and possibly macrophages. The demonstrated multipotency of this cell population in vivo in the context of traumatic brain injury has implications for regenerative therapies, but additional stimulation appears necessary to promote neuronal differentiation outside normally neurogenic regions.

Characterization of a bilateral penetrating brain injury in rats and evaluation of a collagen biomaterial for potential treatment.

Penetrating brain injury (PBI) encountered in both the military and civilian sectors results in high morbidity and mortality due to the absence of effective treatment options for survivors of the initial trauma. Developing therapies for such injuries requires a better understanding of the complex pathology involved when projectiles enter the skull and disrupt the brain parenchyma. This study presents a histological characterization of bilateral PBI using a relatively new injury model in the rat, and also investigates the implantation of a collagen scaffold into the PBI lesion as a potential treatment option. At 1 week post-PBI, the lesion was characterized by dense macrophage infiltration, evolving astrogliosis, hypervascularity, and an absence of viable neurons, oligodendrocytes, and myelinated axons. Histomorphometric analysis revealed that the PBI lesion volume expanded by 29% between 1 week and 5 weeks post-injury, resulting in formation of a large acellular cavity. Immunohistochemistry showed a decrease in the presence of CD68-positive macrophages from 1 to 5 weeks post-PBI as the necrotic tissue in the lesion was cleared, while persistent glial scarring remained in the form of upregulated GFAP expression surrounding the PBI cavity. Implanted type I collagen scaffolds remained intact with open pores after time periods of 1 week and 4 weeks in vivo, and were found to be sparsely infiltrated with macrophages, astrocytes, and endothelial cells. Collagen scaffolds appear to be an appropriate delivery vehicle for cellular and pharmacological therapeutic agents in future studies of PBI.

Incremental adaptation to yaw head turns during 30 RPM centrifugation.

A 3-day incremental protocol was conducted with the aim of adapting human subjects to make head movements comfortably during 30 RPM centrifugation. With motion sickness as a potentially limiting factor, the protocol was designed using a quantitative motion sickness model based upon the neural mismatch sensory conflict theory. Centrifuge velocity was incremented from 14 RPM on day 1, to 23 RPM on day 2, to 30 RPM on day 3, with subjects making a total of 42 head movements on each day. Twenty-four subjects completed the experiment with average motion sickness levels below five (out of 20). Four subjects aborted due to motion sickness. Adaptation of non-compensatory vertical nystagmus was observed through an 18% decrease in the vertical aVOR time constant over the 3 days. Subjective intensity ratings for the head movements decreased by approximately 40% over the 3 days, while illusory motion duration decreased by 18%. Feasibility of head movements during 30 RPM rotation was demonstrated with only 3 days of incremental training.

Effect of loading rate on the compressive mechanics of the immature baboon cervical spine.

Thirty-four cervical spine segments were harvested from 12 juvenile male baboons and compressed to failure at displacement rates of 5, 50, 500, or 5000 mm/s. Compressive stiffness, failure load, and failure displacement were measured for comparison across loading rate groups. Stiffness showed a significant concomitant increase with loading rate, increasing by 62% between rates of 5 and 5000 mm/s. Failure load also demonstrated an increasing relationship with loading rate, while displacement at failure showed no rate dependence. These data may help in the development of improved pediatric automotive safety standards and more biofidelic physical and computational models.

Clinical utility of somatostatin receptor scintigraphic imaging (octreoscan) in esthesioneuroblastoma: a case study and survey of somatostatin receptor subtype expression.

BACKGROUND: For tumors that express somatostatin receptors (SSTR), radiolabeled somatostatin analogs, such as 111In-pentetreotide, can demonstrate the presence of tumor by radioligand uptake using somatostatin receptor scintigraphy (SRS). The use of 111In-pentetreotide for SRS depends on the specific high affinity of octreotide for SSTR subtypes 2, 3, and 5. Of these, SSTR2 has the greatest affinity for octreotide and the greatest relevance for tumor detection with Octreoscan imaging. Discriminating between postoperative changes and residual or recurrent tumor after extensive skull base surgery is often difficult, but in a case of recurrent esthesioneuroblastoma (ENB) we found the use of Octreoscan imaging clinically useful. To better define the general relevance of this imaging technique in this setting, we analyzed SSTR subtype expression in a panel of ENB tumors. METHODS: The case history and correlations between MRI and 111In-pentetreotide SRS of a patient with recurrent ENB were reviewed. The expression pattern of the SSTR subtypes in a panel of ENB tumors was then analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) to better define the potential of more general use of Octreoscan for imaging ENB. To correlate SSTR2 protein expression with 111In-pentetreotide uptake, immunohistochemistry to detect SSTR2 was performed on tumor samples from regions of increased uptake on Octreoscan. RESULTS: The SSTR2 message was expressed at high levels in all five ENB tumor samples, and either SSTR2 protein or histologic findings typical for ENB were found in all tumor tissue obtained from regions of increased 111In-pentetreotide uptake. Furthermore, Octreoscan imaging in this case proved useful in clinical decision making. CONCLUSION: The expression pattern of SSTR2 and the specificity of the Octreoscan for regions of active tumor growth support further investigation of the utility of Octreoscan imaging in the diagnosis and surveillance of ENB. Recent advances in novel therapies based on SSTR ligand binding also provide the rationale to consider such novel therapeutic approaches in patients with ENB.