Publications by authors named "Christopher J Palestro"

105 Publications

At last, 18F-FDG for Inflammation and Infection!

J Nucl Med 2021 Apr 23. Epub 2021 Apr 23.

Long Island Jewish Medical Center, United States.

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http://dx.doi.org/10.2967/jnumed.121.262446DOI Listing
April 2021

Comparison and validation of automated scoring of SPECT phantom cold rod visibility.

Med Phys 2021 Jun 7;48(6):2838-2846. Epub 2021 Apr 7.

Department of Radiology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, 11549, USA.

Purpose: Evaluation of phantom image quality is an integral component of the quality assurance of SPECT systems. This evaluation often is done by visual assessment of the resolution of known structures of a specified size, such as arrays of cold rods in a warm background. Although this method is rapid and convenient, it is qualitative and is subject to inter- and intraobserver variability. Thus an automated quantitative analysis would be preferable. Several metrics of cold rod visibility have been developed, although their suitability for SPECT quality assurance depends on how well they correspond to visual scoring by experienced observers.

Methods: Various metrics of cold rod visibility, derived from either texture analysis or template-based analysis, were investigated. The texture analysis methods measured the normalized gray-level co-occurrence matrix (GLCM) energy ("Energy%") and entropy ("Entropy%") of each region and an associated combination of the two ("EnergyEntropy%"). One template-based method measured the rods-to-background contrast ("Contrast") and an associated visibility index (Contrast × area = "Contrast Visibility"). Another template-based method performed binary classification (BC) of the rods and background to compute the area under curve (AUC) of its receiver operating characteristics (ROC) curve ("BC-AUC") and the corresponding signal-to-noise ratio ("BC-SNR"). All these metrics were computed for 90 SPECT acquisitions of the standard American College of Radiology ("Jaszczak") phantom. Cold rod visibility was scored independently by two experienced nuclear medicine physicists on both dichotomous and 5-point scales. Scoring was performed twice by each observer to evaluate variability.

Results: Interobserver agreement (Cohen's kappa statistic) was 0.78, and intraobserver reproducibility was 0.86 and 0.88, respectively, for each observer. Mean and median scores differed significantly between observers. Accuracy of each metric was assessed according to AUC of ROC analysis with respect to mean dichotomous score. The binary classification metrics had the highest accuracy (BC-AUC = 0.995, BC-SNR = 0.994), above that of the texture analysis metrics (Entropy% = 0.992, Energy% = 0.988, EnergyEntropy% = 0.992) and conventional template analysis (Contrast = 0.984, Contrast Visibility = 0.989). The metrics were similar in terms of rank correlation to mean visibility score. BC-AUC correlated linearly with mean visibility score (R  = 0.95) and consistently performed among the highest of the metrics vs rod diameter and count level.

Conclusions: Automated quantitative analysis of SPECT phantom cold rods correlated well with visual scoring. The metrics based on binary classification performed particularly well for this task, across the range of rod diameters and count levels. The suboptimal interobserver agreement highlights the importance of developing automated algorithms for evaluating scanner performance.
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http://dx.doi.org/10.1002/mp.14776DOI Listing
June 2021

A pilot study treatment of malignant tumors using low-dose F-fluorodeoxyglucose (F-FDG).

Am J Nucl Med Mol Imaging 2020 15;10(6):334-341. Epub 2020 Dec 15.

Medical Oncology, Weill Cornell Medical College (WCMC) New York, NY, USA.

Photons, electrons and protons have therapeutic use however positrons have only been used for diagnostic imaging purposes. The energies of positrons (β) from F-18 (0.633 MeV) and electrons (β) from I-131 (0.606 MeV) are very close and have similar equilibrium dose constants. Since [F]-fluorodeoxyglucose (F-FDG) clears rapidly from circulation, administration of 37-74 GBq (1-2 Ci) of F-FDG is relatively safe from an internal radiation dosimetry point of view. We initiated a phase I dose escalation study to assess the safety, toxicity, and potential therapeutic utility of administering 100-200 mCi/m F-FDG delivered over a 1 to 5 day period in patients with advanced lymphomas and solid tumors refractory to standard of care treatment (SCT). Here we report the results of the first four patients treated. Four patients with advanced cancers received a single dose of 3.7-7.4 GBq/m (100-200 mCi/m) F-FDG. We monitored the patients for adverse effects and for response. No treatment-related toxicities were observed. There was no increased radiation exposure to personnel. Two patients showed decrease in the index lesions' SUVs by 17-33% (Day 1) and 25-31% (Day 30) post treatment. The two other patients showed stable disease on F-PET-CT. Interestingly, responses were seen at low radiotherapy doses (below 1 Gy). This exploratory study demonstrated the safety of therapeutic administration of up to 14.2 GBq (385 mCi) F-FDG. In patients with F-FDG-avid cancers, targeted radionuclide F-FDG therapy appears safe and may offer clinical benefit.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724279PMC
December 2020

Labeled Leukocyte Imaging: Dawn of an Era.

J Nucl Med 2020 12;61(Suppl 2):57S-58S

Donald and Barbara Zucker School of Medicine, Hofstra University and Northwell Health, Hempstead, New York

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http://dx.doi.org/10.2967/jnumed.120.249797DOI Listing
December 2020

The Role of Imaging Techniques to Define a Peri-Prosthetic Hip and Knee Joint Infection: Multidisciplinary Consensus Statements.

J Clin Med 2020 Aug 6;9(8). Epub 2020 Aug 6.

Nuclear Medicine Unit Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, "Sapienza" University of Rome, 00161 Rome, Italy.

Diagnosing a peri-prosthetic joint infection (PJI) remains challenging despite the availability of a variety of clinical signs, serum and synovial markers, imaging techniques, microbiological and histological findings. Moreover, the one and only true definition of PJI does not exist, which is reflected by the existence of at least six different definitions by independent societies. These definitions are composed of major and minor criteria for defining a PJI, but most of them do not include imaging techniques. This paper highlights the pros and cons of available imaging techniques--ray, ultrasound, computed tomography (CT), Magnetic Resonance Imaging (MRI), bone scintigraphy, white blood cell scintigraphy (WBC), anti-granulocyte scintigraphy, and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), discusses the added value of hybrid camera systems-single photon emission tomography/computed tomography (SPECT/CT), PET/CT and PET/MRI and reports consensus answers on important clinical questions that were discussed during the Third European Congress on Inflammation/Infection Imaging in Rome, December 2019.
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http://dx.doi.org/10.3390/jcm9082548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466174PMC
August 2020

Early onset of left ventricular regional asynchrony in arteries with sub-clinical stenosis.

J Nucl Cardiol 2021 Jun 23;28(3):1040-1050. Epub 2020 Jul 23.

Department of Radiology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.

Background: Asynchrony has been reported to be a marker of ischemic-induced left ventricular dysfunction, the magnitude of which correlates with extent of epicardial coronary disease. We wished to determine whether normal-appearing arterial territories with mild degrees of asynchrony have lower Rb PET absolute myocardial blood flow (MBF) and/or lower myocardial flow reserve (MFR).

Methods And Results: Data were examined retrospectively for 105 patients evaluated for known/suspected CAD who underwent rest/regadenoson-stress Rb PET/CT and quantitative coronary angiography. Rest and stress absolute MBF and MFR were quantified from first-pass Rb PET curves. Regional relative myocardial perfusion summed stress score (SSS), summed rest score (SRS), regional phase bandwidth (BW), and regional semi-quantitative asynchrony visual scores of (Asynch) were assessed. We found that in apparently normal arteries (SSS < 4, SRS < 4 and stenosis < 70%), those with abnormally low MFR < 2.0 compared to those with MFR ≥ 2.0 had larger phase BW (186 ± 79° vs 158 ± 67°, P = .02), and more visually apparent Asynch (5.7 ± 4.2 vs 3.9 ± 3.6, P = .02), which was associated with increasing stenosis values (ρ = 0.44, P < .0001).

Conclusion: A subgroup of coronary territories with normal relative perfusion and normal or non-obstructive coronary disease may have reduced MFR, which is signaled physiologically by a mild degree of left ventricular asynchrony.
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http://dx.doi.org/10.1007/s12350-020-02251-9DOI Listing
June 2021

Cardiac amyloidosis CT sign.

Clin Res Cardiol 2020 Jul 13. Epub 2020 Jul 13.

Department of Radiology, North Shore University Hospital, Northwell Health, Zucker School of Medicine at Hofstra/Northwell, 300 Community Drive, Manhasset, NY, 11030, USA.

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http://dx.doi.org/10.1007/s00392-020-01693-yDOI Listing
July 2020

Molecular Imaging of Infection: The First 50 Years.

Semin Nucl Med 2020 01 25;50(1):23-34. Epub 2019 Oct 25.

Department of Radiology, Donald and Barbara Zucker at Hofstra/Northwell, Hempstead, NY. Electronic address:

Despite significant advances in the understanding of microorganisms and an increased availability of antimicrobial therapy, infection remains a major cause of morbidity and mortality. The diagnosis can be challenging and imaging studies often are used for confirmation and localization. For nearly 50 years, molecular imaging agents have played an important role in the diagnosis of infection. Gallium-67 citrate was perhaps the first molecular imaging agent used for diagnosing and localizing infection. Poor imaging characteristics, along with a lack of specificity, and the long (usually 48-72 hours) interval between administration and imaging motivated investigators to search for alternatives. Currently the role of Ga is limited to differentiating acute tubular necrosis from interstitial nephritis and as an alternative to F-FDG for indications, such as sarcoid, spondylodiscitis, and fever of unknown origin, when the latter is not available. The development, in the mid-1970s, of techniques for radiolabeling leukocytes that subsequently migrate to foci of infection was a significant advance and labeled leukocyte imaging still has a preeminent role in molecular imaging of infection. There are significant disadvantages to in-vitro labeled leukocyte imaging. Efforts devoted to developing in-vivo leukocyte labeling methods, however, met with only limited success. Over the past 20 years F-FDG has established itself as the molecular imaging agent of choice for fever of unknown origin, vasculitis, sarcoid, and spondylodiscitis. As useful as these agents are, their uptake is based on the host response to infection, not infection itself. Previous attempts at developing infection specific agents, including radiolabeled antibiotics, antibiotics, and vitamins like biotin were limited by poor results and/or limited availability and so investigators continue to focus on developing infection specific molecular imaging agents. Initial results with radiolabeled nucleoside analogs, sugars, and amino acids, and a renewed interest in radiolabeled antibiotics for both diagnosis and monitoring treatment are exciting and hold great promise for the future.
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http://dx.doi.org/10.1053/j.semnuclmed.2019.10.002DOI Listing
January 2020

Molecular imaging of bacterial infections: Overcoming the barriers to clinical translation.

Sci Transl Med 2019 09;11(508)

Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Clinical diagnostic tools requiring direct sample testing cannot be applied to infections deep within the body, and clinically available imaging tools lack specificity. New approaches are needed for early diagnosis and monitoring of bacterial infections and rapid detection of drug-resistant organisms. Molecular imaging allows for longitudinal, noninvasive assessments and can provide key information about infectious processes deep within the body.
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http://dx.doi.org/10.1126/scitranslmed.aax8251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743081PMC
September 2019

Texture analysis for automated evaluation of Jaszczak phantom SPECT system tests.

Med Phys 2019 Jan 6;46(1):262-272. Epub 2018 Dec 6.

Department of Radiology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, 11549, USA.

Purpose: Routine quarterly quality assurance (QA) assessment of single photon emission computed tomography (SPECT) systems includes analysis of multipurpose phantoms containing spheres and rods of various sizes. When evaluated by accreditation agencies, criteria applied to assess image quality are largely subjective. Determining a quantified image characteristic metric that emulates human reader impressions of image quality could be quite useful. Our investigation was conducted to ascertain whether image texture analysis metrics, such as those applied to PET scans to detect neoplasms, could prove helpful in linking qualitative statements of phantom sphere and rod visibility to quantified parameters. Because it is not obvious whether it is preferable to submit reconstructions to accrediting agencies performed using typical clinical (CLIN) protocol processing parameters or to follow agencies' filtered backprojection (FBP) suggestions, we applied texture analysis metrics to determine the degree to which these choices affect equipment capability assessment.

Methods And Materials: Data were processed retrospectively for 125 different Tc-99 m SPECT scans of standardized phantoms for 14 rotating Anger detector systems as part of routine quarterly QA. Algorithms were written to compute several classes of image metrics: quantile curve metrics, image texture analysis gray-level co-occurrence matrix (GLCM) metrics, contrast metrics, and count histogram metrics. For qualitative image scores, two experienced physicists independently graded sphere and rod visibility on a 5-level scale and assigned dichotomous visibility scores, without knowledge of quantified texture analysis metrics or each other's readings. The same phantom was used to collect 15 additional data sets with two dual-detector SPECT/CT systems, reconstructed both by FBP parameters that have been suggested by accrediting agencies and by manufacturers' default settings for CLIN SPECT/CT bone imaging protocols by ordered subsets expectation maximization (OSEM), incorporating attenuation correction using the CT scan. Image characteristics metrics were compared for FBP and CLIN reconstructions.

Results: For spheres, the metric with the strongest rank correlation with 5-level scale readings was the quantile curve slope (ρ = 0.83, P < 0.0001), while for rods it was GLCM Energy normalized to the maximum GLCM Energy value (EnergyNorm) (ρ = -0.88, P < 0.0001). Compared to dichotomous readings, the metric with the highest ROC area under curve (AUC) for spheres was the quantile curve slopes (AUC = 96 ± 1%, sensitivity = 91%, specificity = 90%), and for rods was EnergyNorm (AUC = 98 ± 1%, sensitivity = 92%, specificity = 95%). Image contrast was higher for all sphere sizes and rod EnergyNorm was lower for sectors of intermediate-sized rods for FBP compared to CLIN reconstructions, in agreement with more rods judged to be visible from FBP than CLIN reconstructions (47% vs 33%, P = 0.002).

Conclusions: When preparing to submit quality assurance images of standardized phantoms to accrediting agencies, a reliable gauge of sphere and rod visibility can be predicted accurately using quantified reader-independent image texture analysis metrics, which also provide a useful basis for choosing among alternative image reconstruction options.
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http://dx.doi.org/10.1002/mp.13289DOI Listing
January 2019

Relationship of Rb PET territorial myocardial asynchrony to arterial stenosis.

J Nucl Cardiol 2020 04 26;27(2):575-588. Epub 2018 Jun 26.

Department of Radiology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.

Objective: Rb PET/CT rest/regadenoson-stress data enable quantification of left ventricular rest and stress function, perfusion, and asynchrony. Our study was conducted to determine which parameters best identify patients with multi-vessel disease (MVD) and individual stenosed arteries.

Methods: PET/CT data were reviewed retrospectively for 105 patients referred for evaluation of CAD, who also underwent angiography. % arterial stenosis was determined quantitatively at a core laboratory. Severe stenosis was defined as ≥ 70%, and MVD as 2 or more stenosed arteries. Segmental MBF was calculated from first-pass data for arterial territories. Regional rest and stress systolic and diastolic asynchrony (Asynch) scores were determined from visual examination of phase polar maps.

Results: 65 vessels had stenoses ≥ 70%. 15 patients had MVD. ROC area under curve (ROC AUC) for identifying patients with MVD was 83% for Asynch and 73% for MFR. ROC AUC for identifying individual arterial territories with stenoses ≥ 70% was 81% and 72% for Asynch and MFR.

Conclusion: Rb PET/CT accurately identified patients with MVD and individual stenosed territories, with regional asynchrony measurements contributing significantly to identify patients with CAD.
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http://dx.doi.org/10.1007/s12350-018-1350-4DOI Listing
April 2020

Interpreting I-ioflupane dopamine transporter scans using hybrid scores.

Eur J Hybrid Imaging 2018 21;2(1):10. Epub 2018 May 21.

Department of Radiology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY USA.

Background: Dopamine transporter (DaT) I-FP-CIT scans most commonly are interpreted visually. Alternatively, absolute quantitation of radiopharmaceutical uptake may improve scan accuracy. However, neither approach accomodates dependence of striatal uptake on age and gender. We investigated whether demographic indexing of visual and numerical variables improve discrimination of patients with essential tremor (ET), Parkinson's disease (PD), and dementia with Lewy bodies (DLB).

Methods: Data of 132 consecutive patients undergoing DaT SPECT scans were reviewed retrospectively. The clinical impression in the latest neurology note was utilized as the final clinical diagnosis. Caudate and putamen specific binding ratio (PSBR) were computed. I calibration phantoms were constructed to enable absolute quantitation of putamen radiopharmaceutical uptake. A single experienced nuclear medicine physician graded visual certainty on a 3-level scale. Demographic indexing normalized metrics to published normal PSBR values. Methods were compared by simultaneous ROC analyses to identify the technique of maximal accuracy.

Results: Thirty-four patients (26%) were diagnosed with ET, 85 (64%) with PD, 6 (5%) with multiple system atrophy, and 7 (5%) with DLB. For discriminating DLB from PD, visual analysis was significantly less specific and accurate than the other techniques. However, indexing significantly improved specificity and accuracy of visual scores, such that indexed visual scores were statistically equivalent to all other methods. Indexed PSBR yielded essentially the same results as non-indexed PSBR, for which highest overall test efficacy was achieved.

Conclusions: Our results in this small series of patients with DLB suggest that if I-FP-CIT visual scores are to be used to discriminate DLB from other neurologic disorders, demographic indexing should be applied. However, best results overall are obtained using quantified parameters, regardless of whether or not demographic indexing is applied to these values.
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http://dx.doi.org/10.1186/s41824-018-0028-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960650PMC
May 2018

Guest Editorial on Molecular Imaging of Infection and Inflammation.

Semin Nucl Med 2018 05 27;48(3):198. Epub 2018 Feb 27.

Department of Radiology, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY. Electronic address:

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http://dx.doi.org/10.1053/j.semnuclmed.2018.02.002DOI Listing
May 2018

Letter from the Guest Editor.

Semin Nucl Med 2018 03 11;48(2):84-85. Epub 2017 Dec 11.

Department of Radiology, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY. Electronic address:

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http://dx.doi.org/10.1053/j.semnuclmed.2017.11.005DOI Listing
March 2018

Imaging of Spondylodiscitis.

Semin Nucl Med 2018 03 6;48(2):131-147. Epub 2018 Feb 6.

Department of Radiology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY.

Spondylodiscitis is an infection of the vertebral body or disc and may also involve the epidural space, posterior elements, and paraspinal soft tissues. It is a cause of morbidity and mortality, and warrants early diagnosis and prompt treatment. Diagnosis can be difficult because of nonspecific signs and symptoms. Magnetic resonance imaging is sensitive and specific and is the imaging modality of choice for spondylodiscitis. Gadolinium contrast can show the extent of soft tissue and bone phlegmon and abscess. The test is less useful for evaluating treatment response. When magnetic resonance imaging cannot be performed or is not diagnostic, radionuclide imaging is a useful alternative. Although bone scintigraphy frequently is used as a screening test, false-negative results can occur, especially in the elderly. This test is not useful for detecting soft tissue infections that accompany or mimic spondylodiscitis. Gallium-67 citrate improves the specificity of the bone scan, can detect infection earlier than the bone scan, may be more sensitive, especially in elderly patients, and identifies accompanying soft tissue infection. Performing SPECT and SPECT/CT improves accuracy. The 2- to 3-day delay between radiopharmaceutical administration and the relatively poor image quality are significant disadvantages of gallium-67. Indium-111 biotin, alone or in combination with streptavidin, accurately diagnoses spondylodiscitis; unfortunately, this agent is not widely available. Currently, F-FDG imaging is the radionuclide test of choice for spondylodiscitis. The procedure, which is completed in a single session, is sensitive, has a high negative predictive value, and reliably differentiates degenerative from infectious vertebral body end plate abnormalities. In comparative investigations, F-FDG has outperformed bone and gallium-67 imaging. Preliminary data suggest that F-FDG may be able to provide an objective means to measure response to treatment. Gallium-68 citrate and 99mTc-radiolabeled antimicrobial peptides have been investigated, but their role in spondylodiscitis has yet to be established.
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http://dx.doi.org/10.1053/j.semnuclmed.2017.11.001DOI Listing
March 2018

A humanized mouse model of liver fibrosis following expansion of transplanted hepatic stellate cells.

Lab Invest 2018 04 19;98(4):525-536. Epub 2018 Jan 19.

Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Diabetes Center, Cancer Center, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Institute for Clinical and Translational Research, Albert Einstein College of Medicine, Bronx, NY, USA.

Hepatic stellate cells (HSCs) are major contributors to liver fibrosis, as hepatic injuries may cause their transdifferentiation into myofibroblast-like cells capable of producing excessive extracellular matrix proteins. Also, HSCs can modulate engraftment of transplanted hepatocytes and contribute to liver regeneration. Therefore, understanding the biology of human HSCs (hHSCs) is important, but effective methods have not been available to address their fate in vivo. To investigate whether HSCs could engraft and repopulate the liver, we transplanted GFP-transduced immortalized hHSCs into immunodeficient NOD/SCID mice. Biodistribution analysis with radiolabeled hHSCs showed that after intrasplenic injection, the majority of transplanted cells rapidly translocated to the liver. GFP-immunohistochemistry demonstrated that transplanted hHSCs engrafted alongside hepatic sinusoids. Prior permeabilization of the sinusoidal endothelial layer with monocrotaline enhanced engraftment of hHSCs. Transplanted hHSCs remained engrafted without relevant proliferation in the healthy liver. However, after CCl or bile duct ligation-induced liver damage, transplanted hHSCs expanded and contributed to extracellular matrix production, formation of bridging cell-septae and cirrhosis-like hepatic pseudolobules. CCl-induced injury recruited hHSCs mainly to zone 3, whereas after bile duct ligation, hHSCs were mainly in zone 1 of the liver lobule. Transplanted hHSCs neither transdifferentiated into other cell types nor formed tumors in these settings. In conclusion, a humanized mouse model was generated by transplanting hHSCs, which proliferated during hepatic injury and inflammation, and contributed to liver fibrosis. The ability to repopulate the liver with transplanted hHSCs will be particularly significant for mechanistic studies of cell-cell interactions and fibrogenesis within the liver.
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http://dx.doi.org/10.1038/s41374-017-0010-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526950PMC
April 2018

Nuclear Medicine Imaging in Fever of Unknown Origin: The New Paradigm.

Curr Pharm Des 2018 ;24(7):814-820

Associate Professor of Radiology, Albert Einstein College of Medicine, Bronx, New York, United States.

Fever of Unknown Origin, or FUO, is a challenging condition for patients and clinicians. In up to 50% of cases, no diagnosis is established. Patient workup begins with comprehensive history, physical examination and laboratory tests. Radionuclide imaging has been a second-line procedure. Gallium-67 citrate, which accumulates in infection, inflammation, and tumor, was for many years, the radionuclide test of choice in the workup of FUO. The 24-72 hours between injection and imaging, relatively high radiation dose to patients, and suboptimal image quality are significant disadvantages; imaging results are variable. Although labeled leukocyte imaging accurately localizes infection, infections cause only about 20%-40% of all FUO's. In most cases, this test is not helpful in identifying the source of the fever. Fluorine-18-fluorodeoxyglucose (FDG) uptake is related to cellular glucose metabolism. Increased FDG uptake is present in numerous hypermetabolic conditions, including tumor, infection, and noninfectious inflammation. FDG positron emission tomography (PET) and PET/computed tomography (CT) have rapidly assumed an increasingly important role in the diagnostic workup of patients with FUO. FDG is especially useful for localizing lesions and areas of interest for further evaluation. In contrast to gallium and labeled leukocyte imaging, FDG contributes useful information in children with FUO. Initially utilized as a second-line diagnostic tool in patients with FUO, recent data indicate that FDG contributes more diagnostically useful information than anatomic imaging like ultrasound and CT, which leads to earlier institution of appropriate therapy. These findings suggest that FDG imaging should be performed earlier, rather than later, in the diagnostic evaluation of the patient with FUO.
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http://dx.doi.org/10.2174/1381612824666171129194507DOI Listing
September 2019

Role of Nuclear Medicine for Diagnosing Infection of Recently Implanted Lower Extremity Arthroplasties.

Semin Nucl Med 2017 11 26;47(6):630-638. Epub 2017 Jul 26.

Albert Einstein College of Medicine, Bronx, NY.

Infection is an infrequent complication of lower extremity prosthetic joint surgery. Approximately one-third develop within 3 months (early), another third within 1 year (delayed), and the remainder more than 1 year (late) after surgery. Diagnosing prosthetic joint infection, especially in the early postoperative period during the first year, is challenging. Pain is almost always present. The presence of fever is variable, ranging from less than 5% to more than 40% of patients. Leukocytosis is a poor predictor of infection. After primary uncomplicated arthroplasty, the C-reactive protein remains elevated for up to 3 weeks. The erythrocyte sedimentation rate can remain elevated for up to 1 year. Although joint aspiration with culture, the definitive preoperative diagnostic procedure, is specific, its sensitivity is variable. Plain radiographs lack sensitivity and specificity. Radionuclide studies are useful for evaluating painful joint replacements, but data on their utility during the early postoperative period are limited. During the first year after arthroplasty insertion, the bone scan can exclude infection. It is a good "rule-out" test, but it is not reliable for "ruling in" infection. Gallium-67 accumulates in normally healing surgical incisions and in aseptic inflammation. With an accuracy of 60%-80% for diagnosing prosthetic joint infection, there is little role for this radiopharmaceutical for evaluating prosthetic joints, regardless of age. Although data about diagnosing prosthetic joint infection with F-FDG in the early postoperative period are lacking, uptake of this radiopharmaceutical in a variety of postoperative settings for variable time periods is well known. Furthermore, its utility for diagnosing prosthetic joint infection in general, after nearly 2 decades of investigation, remains to be established. Indium-111-labeled leukocytes do not accumulate in normally healing surgical wounds, and in combination with marrow imaging, the test is about 90% accurate for diagnosing prosthetic joint infection. Preliminary data indicate a comparable accuracy in the early postoperative period.
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http://dx.doi.org/10.1053/j.semnuclmed.2017.07.008DOI Listing
November 2017

A retrospective analysis of the accuracy of radioactively labeled autologous leukocytes in patients with infected prosthetic joints.

Nucl Med Rev Cent East Eur 2017 ;20(2):81-87

ISOTOPIX - Institute for Nuclear Medicine, Vienna, Mariannengasse 30, A-1090, Vienna, Austria; Department of Nuclear Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Background: Labeled leukocyte scintigraphy (LS) is considered a valuable tool in preoperative diagnosis of prosthetic joint infections (PJI). The aim of this study was to determine the accuracy of LS combined with bone marrow scintigraphy (BMS), as well as inflammation markers CRP and WBC, in detecting infection in patients with prosthetic joints.

Material And Methods: This study included patients suspected of having PJI between January and September 2013 at the Vienna General Hospital who underwent imaging with 99mTc-HMPAO labeled autologous leukocytes and subsequent BMS. Diagnostic accuracy was assessed in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).

Results: A total of 48 patients were included. The most common joint investigated was knee (25), followed by hip (9), shoulder (2), and elbow (1). Other parts of the body investigated included the femur (6), tibia (2), leg (2), and foot (1). The pathogens most frequently isolated included Staphylococcus epidermidis and Candida albicans. The sensitivity of LS was 60%, specificity 97%, PPV 86% and NPV 90%. Overall accuracy was calculated to be 90%.

Conclusions: This study was able to demonstrate that 99mTc-HMPAO labeled autologous leukocytes in patients presenting with symptoms of PJI is accurate. In contrast, however, inflammation markers CRP and WBC are not accurate pre-diagnostic markers for PJI.
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http://dx.doi.org/10.5603/NMR.2017.0013DOI Listing
January 2018

Alternative Means of Estimating I Maximum Permissible Activity to Treat Thyroid Cancer.

J Nucl Med 2017 10 13;58(10):1588-1595. Epub 2017 Apr 13.

Hofstra Northwell School of Medicine of Hofstra University, Manhasset and New Hyde Park, New York.

To protect bone marrow from overirradiation, the maximum permissible activity (MPA) of I to treat thyroid cancer is that which limits the absorbed dose to blood (as a surrogate of marrow) to less than 200 cGy. The conventional approach (method 1) requires repeated γ-camera whole-body measurements along with blood samples. We sought to determine whether reliable MPA values can be obtained by simplified procedures. Data acquired over multiple time points were examined retrospectively for 65 thyroid cancer patients, referred to determine I uptake and MPA for initial treatment after thyroidectomy ( = 39), including 17 patients with compromised renal function and 22 patients with known ( = 16) or suspected ( = 6) metastases. The total absorbed dose to blood (D) was the sum of mean whole-body γ-ray dose component (D) from uncollimated γ-camera measurements and dose due to β emissions (D) from blood samples. Method 2 estimated D from D alone, method 3 estimated D from D alone, and method 4 estimated D from a single 48-h γ-camera measurement. MPA was computed as 200 cGy/D for each D estimate. Method 2 had the strongest correlation with conventional method 1 ( = 0.98) and values similar to method 1 (21.0 ± 13.7 cGy/GBq vs. 21.0 ± 14.1 cGy/GBq, = 0.11), whereas method 3 had a weaker ( = 0.001) correlation ( = 0.94) and method 4 had the weakest ( < 0.0001) correlation ( = 0.69) and lower dose (16.3 ± 14.8 cGy/GBq, < 0.0001). Consequently, correlation with method 1 MPA was strongest for method 2 MPA ( = 0.99) and weakest for method 4 ( = 0. 75). Method 2 and method 1 values agreed equally well regardless of whether patients had been treated with I previously or had abnormal renal function. Because MPA based on blood measurements alone is comparable to MPA obtained with combined body counting and blood sampling, blood measurements alone are sufficient for determining MPA.
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http://dx.doi.org/10.2967/jnumed.117.192278DOI Listing
October 2017

Rb-82 PET/CT left ventricular mass-to-volume ratios.

Int J Cardiovasc Imaging 2017 Aug 7;33(8):1263-1270. Epub 2017 Feb 7.

Division of Nuclear Medicine and Molecular Imaging, Northwell Health, 270-05 76th Avenue, New Hyde Park, NY, 11040, USA.

Left ventricular (LV) mass:volume ratios indexed to body size (Mi/Vi) provide risk stratification for cardiac events. We sought to determine whether Rb-82 PET mass and volume indices are similar to MRI normal values for low likelihood subjects, and whether abnormal indices are related to abnormal myocardial blood flow (MBF). Data were analyzed retrospectively for 194 patients referred for rest/stress Rb-82 PET. LV EF, volume and mass values were calculated and mass:volume ratios were indexed to patients' height and weight. MBF was computed from the first pass dynamic component of PET data. 53 patients at low likelihood of CAD had PET Mi/Vi = 1.35 ± 0.27, consistent with the MRI literature range of 1.0-1.5. Compared to patients with normal indexed volume (Vi), patients with abnormally high Vi had lower rest MBF (0.56 ± 0.24 vs 0.93 ± 0.57 ml/g/min, p = 0.0001), and lower stress MBF (0.97 ± 0.52 vs. 1.83 ± 0.96 ml/g/min, p < 0.0001). Stress EF < 50% predicted abnormal Vi with 90% accuracy. Patients with Mi/Vi < 1.0 had abnormally low rest EF (45 ± 16% vs. 60 ± 15%, p < 0.0001) and low rest MBF (0.58 ± 0.25 vs. 0.96 ± 0.59 ml/g/min, p < 0.0001). In our study population, abnormal LV volume and mass correlated with lower rest and stress MBF and EF, suggesting that the pathophysiologic explanation of these patients' increased risk is more extensive obstructive CAD.
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http://dx.doi.org/10.1007/s10554-017-1087-1DOI Listing
August 2017

Reply: The Ongoing Misperception That Labeled Leukocyte Imaging Is Superior to 18F-FDG PET for Diagnosing Prosthetic Joint Infection.

J Nucl Med 2017 01 22;58(1):182-183. Epub 2016 Sep 22.

Long Island Jewish Medical Center 270-05 76th Ave. New Hyde Park, NY 11040 E-mail:

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http://dx.doi.org/10.2967/jnumed.116.181669DOI Listing
January 2017

Radionuclide Imaging of Musculoskeletal Infection: A Review.

J Nucl Med 2016 09 7;57(9):1406-12. Epub 2016 Jul 7.

Department of Radiology, Hofstra Northwell School of Medicine, Hempstead, New York

There are numerous imaging tests for diagnosing musculoskeletal infection. Radiographs are routinely performed, because even when not diagnostic, they provide an anatomic overview of the region of interest that could influence subsequent procedure selection and interpretation. MRI is sensitive and provides superb anatomic detail. Bone scintigraphy accurately diagnoses osteomyelitis in bones not affected by underlying conditions. (67)Ga is used primarily for spondylodiskitis. Although in vitro labeled leukocyte imaging is the radionuclide test of choice for complicating osteomyelitis such as diabetic pedal osteomyelitis and prosthetic joint infection, it is not useful for spondylodiskitis. Antigranulocyte antibodies and antibody fragments have limitations and are not widely available. (111)In-biotin is useful for spondylodiskitis. Radiolabeled synthetic fragments of the antimicrobial peptide ubiquicidin are promising infection-specific agents. (18)F-FDG is the radiopharmaceutical of choice for spondylodiskitis. Its role in diabetic pedal osteomyelitis and prosthetic joint infection is not established. Preliminary data suggest (68)Ga may be useful in musculoskeletal infection. (124)I-fialuridine initially showed promise as an infection-specific radiopharmaceutical, but subsequent investigations were disappointing. The development of PET/CT and SPECT/CT imaging systems, which combine anatomic and functional imaging, has revolutionized diagnostic imaging. These hybrid systems are redefining the diagnostic workup of patients with suspected or known infection and inflammation by improving diagnostic accuracy and influencing patient management.
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http://dx.doi.org/10.2967/jnumed.115.157297DOI Listing
September 2016

Effect of Outflow Tract Contributions to 82Rb-PET Global Myocardial Blood Flow Computations.

J Nucl Med Technol 2016 Jun 10;44(2):78-84. Epub 2016 Mar 10.

Division of Nuclear Medicine and Molecular Imaging, Northwell Health, Manhasset and New Hyde Park, New York.

Unlabelled: Algorithms are able to compute myocardial blood flow (MBF) from dynamic PET data for each of the 17 left ventricular segments, with global MBF obtained by averaging segmental values. This study was undertaken to compare MBFs with and without the basal-septal segments.

Methods: Data were examined retrospectively for 196 patients who underwent rest and regadenoson-stress (82)Rb PET/CT scanning for evaluation of known or suspected coronary artery disease. MBF data were acquired in gated list mode and rebinned to isolate the first-pass dynamic portion. Coronary vascular resistance (CVR) was computed as mean arterial pressure divided by MBF. MBF inhomogeneity was computed as the ratio of SD to mean MBF. Relative perfusion scores were obtained using (82)Rb-specific normal limits applied to polar maps of myocardial perfusion generated from myocardial equilibrium portions of PET data. MBF and CVRs from 17 and 14 segments were compared.

Results: Mean MBFs were lower for 17- than 14-segment means for rest (0.78 ± 0.50 vs. 0.85 ± 0.54 mL/g/min, paired t test P < 0.0001) and stress (1.50 ± 0.88 vs. 1.67 ± 0.96 mL/g/min, P < 0.0001). Bland-Altman plots of MBF differences versus means exhibited nonzero intercept (-0.04 ± 0.01, P = 0.0004) and significant correlation (r = -0.64, P < 0.0001), with slopes significantly different from 0.0 (-7.2% ± 0.6% and -8.3% ± 0.7% for rest and stress MBF; P < 0.0001). Seventeen-segment CVRs were higher than 14-segment CVRs for rest (159 ± 86 vs. 147 ± 81 mm Hg/mL/g/min, paired t test P < 0.0001) and stress CVR (85 ± 52 vs. 76 ± 48 mm Hg/mL/g/min, P < 0.0001). MBF inhomogeneity correlated significantly (P < 0.0001) with summed perfusion scores, but values correlated significantly more strongly for 14- than 17-segment values for rest (r = 0.67 vs. r = 0.52, P = 0.02) and stress (r = 0.69 vs. r = 0.47, P = 0.001). When basal segments were included in MBF determinations, perfusion inhomogeneity was greater both for rest (39% ± 10% vs. 31% ± 10%, P < 0.0001) and for stress (42% ± 12% vs. 32% ± 11%, P < 0.0001).

Conclusion: Averaging 17 versus 14 segments leads to systematically 7%-8% lower MBF calculations, higher CVRs, and greater computed inhomogeneity. Consideration should be given to excluding basal-septal segments from standard global MBF determination.
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http://dx.doi.org/10.2967/jnmt.116.173005DOI Listing
June 2016

Influence of Multigland Parathyroid Disease on 99mTc-Sestamibi SPECT/CT.

Clin Nucl Med 2016 Apr;41(4):282-8

From the Division of Nuclear Medicine and Molecular Imaging, North Shore-Long Island Jewish Health System, Manhasset and New Hyde Park, NY.

Purpose: 99mcTc-sestamibi (MIBI) imaging is performed for preoperative parathyroid lesion localization in patients with primary hyperparathyroidism. Decreased sensitivity in multigland disease (MGD) compared with single-gland disease (SGD) is well recognized for planar and SPECT imaging, but few data are available on MIBI SPECT/CT in MGD.

Methods: We retrospectively analyzed 246 patients with primary hyperparathyroidism who underwent preoperative MIBI SPECT/CT. Surgical and pathology reports were used to confirm numbers, weights, and locations of excised glands. Two experienced physicians independently read MIBI SPECT/CTs, grading lesion certainty on a 5-point scale ("definitely normal" to "definitely abnormal").

Results: Three hundred one parathyroid lesions were excised at surgery. Thirty-nine patients (16%) had MGD, and 207 patients (84%) had SGD; 26 patients had 2 lesions, 10 had 3 lesions, and 3 had 4 lesions. Lesion weights were significantly lower in MGD than in SGD (390 ± 604 vs 866 ± 933 mg, P < 0.0001) and decreased with increasing numbers of lesions (P < 0.0001). MIBI SPECT/CT was less sensitive for MGD than SGD (66% vs 98%, P < 0.0001). Sensitivity was lower for 66 MGD lesions matched to 66 SGD lesions (64% vs 98%, P < 0.0001) and decreased with increasing lesion numbers (ρ = -0.45, P < 0.0001), despite similar weights (526 ± 678 vs 525 ± 686 mg, P = 0.99) and similar locations (P = 0.47). Specificity was similar for MGD (95%) and SGD (90%).

Conclusions: 99mcTc-MIBI SPECT/CT sensitivity is significantly lower in MGD than in SGD. This does not appear to be related to lesion weight or location.
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http://dx.doi.org/10.1097/RLU.0000000000001115DOI Listing
April 2016

Kupffer Cell Transplantation in Mice for Elucidating Monocyte/Macrophage Biology and for Potential in Cell or Gene Therapy.

Am J Pathol 2016 Mar 7;186(3):539-51. Epub 2016 Jan 7.

Department of Pathology, Albert Einstein College of Medicine, Bronx, New York; Department of Medicine, Marion Bessin Liver Research Center, Cancer Research Center, Diabetes Center, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, and Institute for Clinical and Translational Research, Albert Einstein College of Medicine, Bronx, New York. Electronic address:

Kupffer cells (KC) play major roles in immunity and tissue injury or repair. Because recapitulation of KC biology and function within liver will allow superior insights into their functional repertoire, we studied the efficacy of the cell transplantation approach for this purpose. Mouse KC were isolated from donor livers, characterized, and transplanted into syngeneic recipients. To promote cell engraftment through impairments in native KC, recipients were preconditioned with gadolinium chloride. The targeting, fate, and functionality of transplanted cells were evaluated. The findings indicated that transplanted KC engrafted and survived in recipient livers throughout the study period of 3 months. Transplanted KC expressed macrophage functions, including phagocytosis and cytokine expression, with or without genetic modifications using lentiviral vectors. This permitted studies of whether transplanted KC could affect outcomes in the context of acetaminophen hepatotoxicity or hepatic ischemia-reperfusion injury. Transplanted KC exerted beneficial effects in these injury settings. The benefits resulted from cytoprotective factors including vascular endothelial growth factor. In conclusion, transplanted adult KC were successfully targeted and engrafted in the liver with retention of innate immune and tissue repair functions over the long term. This will provide excellent opportunities to address critical aspects in the biogenesis, fate, and function of KC within their native liver microenvironment and to develop the cell and gene therapy potential of KC transplantation.
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http://dx.doi.org/10.1016/j.ajpath.2015.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816709PMC
March 2016

Relationships between left ventricular asynchrony and myocardial blood flow.

J Nucl Cardiol 2017 02 24;24(1):43-52. Epub 2015 Sep 24.

Division of Nuclear Medicine and Molecular Imaging, North Shore - Long Island Jewish Health System, Manhasset & New Hyde Park, NY, USA.

Objective: Rb PET protocols enable determination of left ventricular asynchrony (LVAS) at rest and stress, along with myocardial blood flow (MBF). We hypothesized that in patients with resting LVAS, MBF differs between those with stress-induced LVAS improvement and those with stress-induced LVAS deterioration.

Methods: We retrospectively analyzed Rb rest/regadenoson stress PET studies of 195 patients evaluated for known or suspected coronary artery disease. MBF was computed from first-pass data; function and relative perfusion were computed from myocardial equilibrium data. LVAS was defined as phase contraction bandwidth (BW) above Rb gender-specific normal limits, with changes defined as BW moving into or out of normal ranges.

Results: Among the 195 patients, 64 had LVAS at rest, of whom 13 reverted to normal and 51 continued to have LVAS with stress. Patients who did not improve had lower stress MBF (1.04 ± 0.69 vs 1.58 ± 0.67, p = .02) and coronary flow reserve (1.94 ± 1.16 vs 3.04 ± 1.22, p = .01) than those who did improve. ROC analysis indicated that the parameter most strongly associated with improvement in asynchrony for patients with resting LVAS was reduction in MBF heterogeneity (ROC area (accuracy) = 84%, sensitivity = 92%, and specificity = 67%).

Conclusion: LVAS is highly correlated with MBF and CVR, with stress-induced improvement in synchronicity most strongly associated with improved MBF homogeneity.
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http://dx.doi.org/10.1007/s12350-015-0270-9DOI Listing
February 2017

Effect of reconstruction algorithms on the accuracy of (99m)Tc sestamibi SPECT/CT parathyroid imaging.

Am J Nucl Med Mol Imaging 2015 15;5(2):195-203. Epub 2015 Jan 15.

Department of Radiology, Hofstra North Shore-LIJ School of Medicine of Hofstra University Hempstead, NY ; Division of Nuclear Medicine and Molecular Imaging, North Shore - Long Island Jewish Health System Manhasset & New Hyde Park, NY, USA.

The superiority of SPECT/CT over SPECT for (99m)Tc-sestamibi parathyroid imaging often is assumed to be due to improved lesion localization provided by the anatomic component (computed tomography) of the examination. It also is possible that this superiority may be related to the algorithms used for SPECT data reconstruction. The objective of this investigation was to determine the effect of SPECT reconstruction algorithms on the accuracy of MIBI SPECT/CT parathyroid imaging. We retrospectively analyzed preoperative MIBI SPECT/CT parathyroid imaging studies performed on 106 patients. SPECT data were reconstructed by filtered back projection (FBP) and by iterative reconstruction with corrections for collimator resolution recovery and attenuation (IRC). Two experienced readers independently graded lesion detection certainty on a 5-point scale without knowledge of each other's readings, reconstruction methods, other test results or final diagnoses. All patients had surgical confirmation of the final diagnosis, including disease limited to the neck, and location and weight of excised lesion(s). There were 135 parathyroid lesions among the 106 patients. For FBP SPECT/CT and IRC SPECT/CT sensitivity was 76% and 90% (p = 0.003), specificity was 87% and 87% (p = 0.90), and accuracy was 83% and 88% (p = 0.04), respectively. Inter-rater agreement was significantly higher for IRC than for FBP (kappa = 0.76, "good agreement", versus kappa = 0.58, "moderate agreement", p < 0.0001). We conclude that the improved accuracy of MIBI SPECT/CT compared to MIBI SPECT for preoperative parathyroid lesion localization is due in part to the use of IRC for SPECT data reconstruction.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396014PMC
May 2015

Radionuclide imaging of osteomyelitis.

Semin Nucl Med 2015 Jan;45(1):32-46

Department of Radiology Hofstra, NorthShore-LIJ School of Medicine, Hempstead, NY; Division of Nuclear Medicine and Molecular Imaging, North Shore Long Island Jewish Health System, Manhasset & New Hyde Park, NY. Electronic address:

Radionuclide procedures frequently are performed as part of the diagnostic workup of osteomyelitis. Bone scintigraphy accurately diagnoses osteomyelitis in bones not affected by underlying conditions. Degenerative joint disease, fracture, and orthopedic hardware decrease the specificity of the bone scan, making it less useful in these situations. Gallium-67 scintigraphy was often used as an adjunct to bone scintigraphy for diagnosing osteomyelitis. However, now it is used primarily for spinal infections when (18)F-FDG imaging cannot be performed. Except for the spine, in vitro-labeled leukocyte imaging is the nuclear medicine test of choice for diagnosing complicating osteomyelitis. Leukocytes accumulate in bone marrow as well as in infection. Performing complementary bone marrow imaging with (99m)Tc-sulfur colloid facilitates the differentiation between osteomyelitis and normal marrow and improves test overall accuracy. Antigranulocyte antibodies and antibody fragments, such as (99m)Tc-besilesomab and (99m)Tc-sulesomab, were developed to eliminate the disadvantages associated with in vitro-labeled leukocytes. These agents, however, have their own shortcomings and are not widely available. As biotin is used as a growth factor by certain bacteria, (111)In-biotin is useful to diagnose spinal infections. Radiolabeled synthetic fragments of ubiquicidin, a naturally occurring human antimicrobial peptide that targets bacteria, can differentiate infection from sterile inflammation and may be useful to monitor response to treatment. (18)F-FDG is extremely useful in the diagnostic workup of osteomyelitis. Sensitivity in excess of 95% and specificity ranging from 75%-99% have been reported. (18)F-FDG is the radionuclide test of choice for spinal infection. The test is sensitive, with a high negative predictive value, and reliably differentiates degenerative from infectious vertebral body end-plate abnormalities. Data on the accuracy of (18)F-FDG for diagnosing diabetic pedal osteomyelitis are contradictory, and its role for this indication remains to be determined. Initial investigations suggested that (18)F-FDG accurately diagnoses prosthetic joint infection; more recent data indicate that it cannot differentiate infection from other causes of prosthetic failure. Preliminary data on the PET agents gallium-68 and iodine-124 fialuridine indicate that these agents may have a role in diagnosing osteomyelitis.
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http://dx.doi.org/10.1053/j.semnuclmed.2014.07.005DOI Listing
January 2015

Diagnosis of abnormal biliary copper excretion by positron emission tomography with targeting of (64)Copper-asialofetuin complex in LEC rat model of Wilson's disease.

Am J Nucl Med Mol Imaging 2014 6;4(6):537-47. Epub 2014 Sep 6.

Marion Bessin Liver Research Center, Diabetes Center, Cancer Research Center, Departments of Medicine and Pathology, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, and Institute for Clinical and Translational Research, Albert Einstein College of Medicine Bronx, NY, USA.

Identification by molecular imaging of key processes in handling of transition state metals, such as copper (Cu), will be of considerable clinical value. For instance, the ability to diagnose Wilson's disease with molecular imaging by identifying copper excretion in an ATP7B-dependent manner will be very significant. To develop highly effective diagnostic approaches, we hypothesized that targeting of radiocopper via the asialoglycoprotein receptor will be appropriate for positron emission tomography, and examined this approach in a rat model of Wilson's disease. After complexing (64)Cu to asialofetuin we studied handling of this complex compared with (64)Cu in healthy LEA rats and diseased homozygous LEC rats lacking ATP7B and exhibiting hepatic copper toxicosis. We analyzed radiotracer clearance from blood, organ uptake, and biliary excretion, including sixty minute dynamic positron emission tomography recordings. In LEA rats, (64)Cu-asialofetuin was better cleared from blood followed by liver uptake and greater biliary excretion than (64)Cu. In LEC rats, (64)Cu-asialofetuin activity cleared even more rapidly from blood followed by greater uptake in liver, but neither (64)Cu-asialofetuin nor (64)Cu appeared in bile. Image analysis demonstrated rapid visualization of liver after (64)Cu-asialofetuin administration followed by decreased liver activity in LEA rats while liver activity progressively increased in LEC rats. Image analysis resolved this difference in hepatic activity within one hour. We concluded that (64)Cu-asialofetuin complex was successfully targeted to the liver and radiocopper was then excreted into bile in an ATP7B-dependent manner. Therefore, hepatic targeting of radiocopper will be appropriate for improving molecular diagnosis and for developing drug/cell/gene therapies in Wilson's disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171840PMC
September 2014