A bis-boron boramino acid PET tracer for brain tumor diagnosis.

PURPOSE: Boramino acids are a class of amino acid biomimics that replace the carboxylate group with trifluoroborate and can achieve the 18F-labeled positron emission tomography (PET) and boron neutron capture therapy (BNCT) with identical chemical structure. METHODS: This study reports a trifluoroborate-derived boronophenylalanine (BBPA), a derived boronophenylalanine (BPA) for BNCT, as a promising PET tracer for tumor imaging. RESULTS: Competition inhibition assays in cancer cells suggested the cell accumulation of [18F]BBPA is through large neutral amino acid transporter type-1 (LAT-1). Of note, [18F]BBPA is a pan-cancer probe that shows notable tumor uptake in B16-F10 tumor-bearing mice. In the patients with gliomas and metastatic brain tumors, [18F]BBPA-PET shows good tumor uptake and notable tumor-to-normal brain ratio (T/N ratio, 18.7 ± 5.5, n = 11), higher than common amino acid PET tracers. The [18F]BBPA-PET quantitative parameters exhibited no difference in diverse contrast-enhanced status (P = 0.115-0.687) suggesting the [18F]BBPA uptake was independent from MRI contrast-enhancement. CONCLUSION: This study outlines a clinical trial with [18F]BBPA to achieve higher tumor-specific accumulation for PET, provides a potential technique for brain tumor diagnosis, and might facilitate the BNCT of brain tumors.

Development of small-molecular-based radiotracers for PET imaging of PD-L1 expression and guiding the PD-L1 therapeutics.

PURPOSE: Programmed cell death protein ligand 1 (PD-L1) is a crucial biomarker for immunotherapy. However, nearly 70% of patients do not respond to PD-L1 immune checkpoint therapy. Accurate monitoring of PD-L1 expression and quantification of target binding during treatment are essential. In this study, a series of small-molecule radiotracers were developed to assess PD-L1 expression and direct immunotherapy. METHODS: Radiotracers of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were designed based on a 2-methyl-3-biphenyl methanol scaffold and successfully synthesized. Cellular experiments and molecular docking assays were performed to determine their specificity for PD-L1. PD-L1 status was investigated via positron emission tomography (PET) imaging in MC38 tumor models. PET imaging of [68Ga]Ga-D-pep-PMED was performed to noninvasively quantify PD-L1 blocking using an anti-mouse PD-L1 antibody (PD-L1 mAb). RESULTS: The radiosyntheses of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were achieved with radiochemical yields of 87 ± 6%, 82 ± 4%, and 79 ± 9%, respectively. In vitro competition assays demonstrated their high affinities (the IC50 values of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were 90.66 ± 1.24, 160.8 ± 1.35, and 51.6 ± 1.32 nM, respectively). At 120 min postinjection (p.i.) of the radiotracers, MC38 tumors displayed optimized tumor-to-muscle ratios for all radioligands. Owing to its hydrophilic modification, [68Ga]Ga-D-pep-PMED had the highest target-to-nontarget (T/NT) ratio of approximately 6.2 ± 1.2. Interestingly, the tumor/liver ratio was hardly affected by different concentrations of the inhibitor BMS202. We then evaluated the impacts of dose and time on accessible PD-L1 levels in the tumor during anti-mouse PD-L1 antibody treatment. The tumor uptake of [68Ga]Ga-D-pep-PMED significantly decreased with increasing PD-L1 mAb dose. Moreover, after 8 days of treatment with a single antibody, the uptake of [68Ga]Ga-D-pep-PMED in the tumor significantly increased but remained lower than that in the saline group. CONCLUSION: PET imaging with [68Ga]Ga-D-pep-PMED, a small-molecule radiotracer, is a promising tool for evaluating PD-L1 expression and quantifying the target blockade of PD-L1 to assist in the development of effective therapeutic regimens.

Peptidic heterodimer-based radiotracer targeting fibroblast activation protein and integrin αvß3.

PURPOSE: Several studies have demonstrated the advantages of heterodimers over their corresponding monomers due to the multivalency effect. This effect leads to an increased number of effective targeted receptors and, consequently, improved tumor uptake. Fibroblast activation protein (FAP) and integrin αvß3 are found to be overexpressed in different components of the tumor microenvironment. In our pursuit of enhancing tumor uptake and retention, we designed and developed a novel peptidic heterodimer that synergistically targets both FAP and integrin αvß3. METHODS: FAP-RGD was synthesized from FAP-2286 and c(RGDfK) through a multi-step organic synthesis. The dual receptor binding property of 68Ga-FAP-RGD was investigated by cell uptake and competitive binding assays. Preclinical pharmacokinetics were determined in HT1080-FAP and U87MG tumor models using micro-positron emission tomography/computed tomography (micro-PET/CT) and biodistribution studies. The antitumor efficacy of 177Lu-FAP-RGD was assessed in U87MG tumor models. The radiation exposure and clinical diagnostic performance of 68 Ga-FAP-RGD were evaluated in healthy volunteers and cancer patients. RESULTS: Bi-specific radiotracer 68Ga-FAP-RGD exhibited high binding affinity for both FAP and integrin αvß3. In comparison to 68Ga-FAP-2286 and 68Ga-RGDfK, 68Ga-FAP-RGD displayed enhanced tumor uptake and longer tumor retention time in preclinical models. 177Lu-FAP-RGD could efficiently suppress the growth of U87MG tumor in vivo when applied at an activity of 18.5 and 29.6 MBq. The effective dose of 68Ga-FAP-RGD was 1.06 × 10-2 mSv/MBq. 68Ga-FAP-RGD demonstrated low background activity and stable accumulation in most neoplastic lesions up to 3 h. CONCLUSION: Taking the advantages of multivalency effect, the bi-specific radiotracer 68Ga-FAP-RGD showed superior tumor uptake and retention compared to its corresponding monomers. Preclinical studies with 68Ga- or 177Lu-labeled FAP-RGD showed favorable image contrast and effective antitumor responses. Despite the excellent performance of 68Ga-FAP-RGD in clinical diagnosis, experimental efforts are currently underway to optimize the structure of FAP-RGD to increase its potential for clinical application in endoradiotherapy.

Feasibility of intraoperative injection of radioactive tracer and blue dye for sentinel lymph node biopsy in vulvar cancer.

OBJECTIVE: The objective of this study was to examine the feasibility and success rate of intraoperative injection of radiotracer and blue dye performed by the surgeon without the use of preoperative lymphoscintigraphy for the detection of sentinel lymph nodes in clinically early stage vulvar cancer. METHODS: All patients with clinically early stage vulvar cancer who underwent attempted sentinel lymph node biopsy using intraoperative injection of Technetium-99 m (99mTc) tracer and blue dye performed by the surgeon after induction of anesthesia at single academic institution from 12/2009 to 5/2022 were identified. Demographic and clinicopathologic variables were collected. Data were compared using descriptive statistics. RESULTS: One hundred sixty-four patients (median age 66.4 years) underwent intraoperative injection of radioactive tracer and dye for sentinel lymph node biopsy. Most patients (n = 156, 95.1%) were white. Squamous cell carcinoma accounted for 138 cases (84.1%), melanoma for 10 (6.1%), extra-mammary invasive Paget's disease for 11 (6.7%), and other histologies for 5 (3%). A majority of cases were stage I disease on final pathology (n = 119, 72.6%). Most patients (n = 117, 71%) had tumors located within 2 cm of the midline and underwent planned bilateral groin assessment, while 47 (29%) had well lateralized lesions and underwent unilateral groin assessment. For the patients undergoing unilateral groin assessment, 44 of 47 (93.6%) had successful unilateral mapping. Of the patients who underwent bilateral groin assessment, 87 of 117 (74.4%) had successful bilateral mapping, and 26 of 117 (22.2%) had successful unilateral mapping. Of the 26 patients who underwent bilateral assessment but only had unilateral mapping, 19 had unilateral mapping to ipsilateral groin but failed contralateral mapping, six had midline lesions with successful mapping to one groin but failed mapping to the other groin, and one had unilateral mapping to the contralateral groin but not ipsilateral groin. The total successful sentinel lymph node mapping rate in this cohort was 86.5% (243/281 total sentinel lymph node attempts). CONCLUSION: In this cohort, the overall success rate of sentinel lymph node mapping and biopsy was 86.5%. The high rate of successful sentinel lymph node mapping supports the use of intraoperative radiotracer and blue dye injection by trained providers.

Cryo-EM Structures of Chronic Traumatic Encephalopathy Tau Filaments with PET Ligand Flortaucipir.

Positron emission tomography (PET) imaging allows monitoring the progression of amyloid aggregation in the living brain. [18F]-Flortaucipir is the only approved PET tracer compound for the visualisation of tau aggregation. Here, we describe cryo-EM experiments on tau filaments in the presence and absence of flortaucipir. We used tau filaments isolated from the brain of an individual with Alzheimer's disease (AD), and from the brain of an individual with primary age-related tauopathy (PART) with a co-pathology of chronic traumatic encephalopathy (CTE). Unexpectedly, we were unable to visualise additional cryo-EM density for flortaucipir for AD paired helical or straight filaments (PHFs or SFs), but we did observe density for flortaucipir binding to CTE Type I filaments from the case with PART. In the latter, flortaucipir binds in a 1:1 molecular stoichiometry with tau, adjacent to lysine 353 and aspartate 358. By adopting a tilted geometry with respect to the helical axis, the 4.7 Å distance between neighbouring tau monomers is reconciled with the 3.5 Å distance consistent with π-π-stacking between neighbouring molecules of flortaucipir.

Airway clearance techniques compared to no airway clearance techniques for cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is an inherited progressive life-limiting disease characterised by the build-up of abnormally thick, sticky mucus affecting mostly the lungs, pancreas, and digestive system. Airway clearance techniques (ACTs), traditionally referred to as chest physiotherapy, are recommended as part of a complex treatment programme for people with CF. The aim of an ACTs is to enhance mucociliary clearance and remove viscous secretions from the airways within the lung to prevent distal airway obstruction. This reduces the infective burden and associated inflammatory effects on the airway epithelia.  There are a number of recognised ACTs, none of which have shown superiority in improving short-term outcomes related to mucus transport. This systematic review, which has been updated regularly since it was first published in 2000, considers the efficacy of ACTs compared to not performing any ACT in adults and children with CF. It is important to continue to review this evidence, particularly the long-term outcomes, given the recent introduction of highly effective modulator therapies and the improved health outcomes and potential changes to CF management associated with these drugs. OBJECTIVES: To determine the effectiveness and acceptability of airway clearance techniques compared to no airway clearance techniques or cough alone in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings, to 17 October 2022. We searched ongoing trials registers (Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform) to 7 November 2022. SELECTION CRITERIA: We included randomised or quasi-randomised studies that compared airway clearance techniques (chest physiotherapy) with no airway clearance techniques or spontaneous cough alone in people with CF. DATA COLLECTION AND ANALYSIS: Both review authors independently assessed study eligibility, extracted data, and assessed the risk of bias of the included studies. We used GRADE methodology to assess the certainty of the evidence. MAIN RESULTS: We included 11 cross-over studies (153 participants) and one parallel study (41 participants). There were differences between studies in how the interventions were delivered, with several intervention groups combining more than one ACT. One study used autogenic drainage; five used conventional chest physiotherapy; nine used positive expiratory pressure (PEP), with one study varying the water pressure between arms; three studies used oscillating PEP; two used exercise; and two used high-frequency chest wall oscillation (HFCWO). Of the 12 included studies, 10 were single-treatment studies, and two delivered the intervention over two consecutive days (once daily in one study, twice daily in the second). This substantial heterogeneity in the treatment interventions precluded pooling of data for meta-analysis. Blinding of participants, caregivers, and clinicians is impossible in airway clearance studies; we therefore judged all studies at unclear risk of performance bias. Lack of information in eight studies made assessment of risk of bias unclear for most other domains.  We rated the certainty of evidence as low or very low due to the short-term cross-over trial design, small numbers of participants, and uncertain risk of bias across most or all domains. Six studies (84 participants) reported no effect on pulmonary function variables following intervention; but one study (14 participants) reported an improvement in pulmonary function following the intervention in some of the treatment groups. Two studies reported lung clearance index: one (41 participants) found a variable response to treatment with HFCWO, whilst another (15 participants) found no effect on lung clearance index with PEP therapy (low-certainty evidence). Five studies (55 participants) reported that ACTs, including coughing, increased radioactive tracer clearance compared to control, while a further study (eight participants) reported no improvement in radioactive tracer clearance when comparing PEP to control, although coughing was discouraged during the PEP intervention. We rated the certainty of evidence on the effect of ACTs on radioactive tracer clearance as very low. Four studies (46 participants) investigated the weight of mucus cleared from the lungs and reported greater secretions during chest physiotherapy compared to a control. One study (18 participants) reported no differences in sputum weight (very low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence from this review shows that ACTs may have short-term effects on increasing mucus transport in people with CF. All included studies had short-term follow-up; consequently, we were unable to draw any conclusions on the long-term effects of ACTs compared to no ACTs in people with CF. The evidence in this review represents the use of airway clearance techniques in a CF population before widespread use of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Further research is needed to determine the effectiveness and acceptability of airway clearance in those treated with highly effective CFTR modulators.

Radionuclide Tracers for Myocardial Perfusion Imaging and Blood Flow Quantification.

Myocardial perfusion imaging by nuclear cardiology is widely validated for the diagnosis, risk stratification, and management of patients with suspected or known coronary artery disease. Numerous radiopharmaceuticals are available for single-photon emission computed tomography and PET modalities. Each tracer shows advantages and limitations that should be taken into account in performing an imaging examination. This review aimed to summarize the state-of-the-art radiotracers used for myocardial perfusion imaging and blood flow quantification, highlighting the new technologic advances and promising possible applications.

α-D-Glucose as a non-radioactive MRS tracer for metabolic studies of the brain.

Changes in brain glucose metabolism occur in many neurological disorders as well as during aging. Most studies on the uptake of glucose in the brain use positron emission tomography, which requires injection of a radioactive tracer. Our study shows that ultra-high-field 1H-MRS can be used to measure α-D-glucose at 5.22 ppm in vivo, and the α-D-glucose can be used as a radiation-free tracer in the human brain.

Partial Response Upon Peptide Receptor Radionuclide Therapy in a Highly Proliferative Pancreatic Neuroendocrine Tumor.

ABSTRACT: We report on a patient diagnosed with an aggressive pancreatic neuroendocrine tumor (NET G3; Ki67 = 60%), who underwent pancreatic resection with partial removal of liver lesions. The patient refused chemotherapy. Dual-tracer imaging with 18 F-FDG and somatostatin receptor (SSTR)-targeted PET/CT was conducted. Radiotracer accumulation on both imaging modalities in bilobar hepatic lesions was observed. "Cold" somatostatin analogues with four cycles of peptide receptor radionuclide therapy (PRRT) were initiated, leading to partial response. Even in highly proliferative but differentiated G3 NET (Ki67>55%), SSTR expression in sites of disease should be evaluated, which may then allow PRRT, even as first-line systemic treatment.

Recent Advances in Bioorthogonal Click Chemistry for Enhanced PET and SPECT Radiochemistry.

Due to their high reaction rate and reliable selectivity, bioorthogonal click reactions have been extensively investigated in numerous research fields, such as nanotechnology, drug delivery, molecular imaging, and targeted therapy. Previous reviews on bioorthogonal click chemistry for radiochemistry mainly focus on 18F-labeling protocols employed to produce radiotracers and radiopharmaceuticals. In fact, besides fluorine-18, other radionuclides such as gallium-68, iodine-125, and technetium-99m are also used in the field of bioorthogonal click chemistry. Herein, to provide a more comprehensive perspective, we provide a summary of recent advances in radiotracers prepared using bioorthogonal click reactions, including small molecules, peptides, proteins, antibodies, and nucleic acids as well as nanoparticles based on these radionuclides. The combination of pretargeting with imaging modalities or nanoparticles, as well as the clinical translations study, are also discussed to illustrate the effects and potential of bioorthogonal click chemistry for radiopharmaceuticals.

Sentinel Lymph Node Identification in Post Neoadjuvant Chemotherapy Breast Cancer Patients Undergoing Surgical Excision Using Lymphosonography.

OBJECTIVES: This study evaluated the efficacy of lymphosonography in the identification of sentinel lymph nodes (SLNs) in post neoadjuvant chemotherapy patients with breast cancer scheduled to undergo surgical excision. METHODS: Seventy-nine subjects scheduled for breast cancer surgery with SLN excision completed this IRB-approved study, out of which 18 (23%) underwent neoadjuvant chemotherapy before surgery. Subjects underwent percutaneous Sonazoid (GE Healthcare) injections around the tumor area for a total of 1.0 mL. Lymphosonography was performed using CPS on an S3000 HELX scanner (Siemens Healthineers) with a linear probe. Subjects received blue dye and radioactive tracer as part of their standard of care. Excised SLNs were classified as positive or negative for the presence of blue dye, radioactive tracer and Sonazoid. The results were compared between methods and pathology findings. RESULTS: Seventy-two SLNs were surgically excised from 18 subjects, 29 were positive for blue dye, 63 were positive for radioactive tracer and 57 were positive for Sonazoid. Comparison with blue dye showed that both radioactive tracer and lymphosonography achieved an accuracy of 53% (P > .50). Comparison with radioactive tracer showed that blue dye had an accuracy of 53%, while lymphosonography achieved an accuracy of 67% (P < .01). Of the 72 SLNs, 15 were determined malignant by pathology; the detection rate was 47% for blue dye (7/15), 67% for radioactive tracer (10/15) and 100% for lymphosonography (15/15) (P < .001). CONCLUSIONS: Lymphosonography achieved similar accuracy as radioactive tracer and higher accuracy than blue dye for identifying SLNs. The 15 SLNs positive for malignancy were all identified by lymphosonography.

89ZED88082A Safely Characterizes Whole-Body CD8+ T-cell Distribution.

The 89ZED88082A antibody tracer allows for imaging of the whole-body distribution of CD8+ T cells.

Sentinel Lymph Node Identification in Patients With Breast Cancer Using Lymphosonography.

The objective of the work described here was to evaluate the efficacy of lymphosonography in identifying sentinel lymph nodes (SLNs) in patients with breast cancer undergoing surgical excision. Of the 86 individuals enrolled, 79 completed this institutional review board-approved study. Participants received subcutaneous 1.0-mL injections of ultrasound contrast agent (UCA) around the tumor. An ultrasound scanner with contrast-enhanced ultrasound (CEUS) capabilities was used to identify SLNs. Participants were administered with blue dye and radioactive tracer to guide SLN excision as standard-of-care. Excised SLNs were classified as positive or negative for the presence of blue dye, radioactive tracer and UCA, and sent for pathology. Two hundred fifty-two SLNs were excised; 158 were positive for blue dye, 222 were positive for radioactive tracer and 223 were positive for UCA. Comparison with blue dye revealed accuracies of 96.2% for radioactive tracer and 99.4% for lymphosonography (p > 0.15). Relative to radioactive tracer, blue dye had an accuracy of 68.5%, and lymphosonography achieved 86.5% (p < 0.0001). Of 252 SLNs excised, 34 were determined to be malignant by pathology; 18 were positive for blue dye (detection rate = 53%), 23 for radioactive tracer (detection rate = 68%) and 34 for UCA (detection rate = 100%) (p < 0.0001). Lymphosonography was similar in accuracy to radioactive tracer and higher in accuracy than blue dye in identifying SLNs. All 34 malignant SLNs were identified by lymphosonography.

Novel 68Ga-FAPI PET/CT Offers Oncologic Staging Without COVID-19 Vaccine-Related Pitfalls.

In the setting of ongoing coronavirus disease 2019 vaccination, vaccine-related tracer uptake in locoregional lymph nodes has become a well-known issue in tumor staging by 18F-FDG PET/CT. 68Ga-fibroblast-activation protein inhibitor (FAPI) PET/CT is a new oncologic imaging tool that may overcome this limitation. Methods: We assessed postvaccine head-to-head and same-day 18F-FDG and 68Ga-FAPI-46 PET/CT findings in a series of 11 patients from a large, prospective imaging registry. All patients with documented tracer uptake in locoregional lymph nodes on PET/CT or PET/MRI, after vaccination within 6 wk, were eligible for investigation. Result: Significant visual lymph node uptake adjacent to the injection site was noted in 11 of 11 (100%) patients with 18F-FDG PET/CT, versus 0 of 11 (0%) with 68Ga-FAPI PET/CT. 18F-FDG detected 73% and 68Ga-FAPI PET/CT 94% of all tumor lesions. Conclusion: In this case-series study, 68Ga-FAPI showed its potential to avoid 18F-FDG PET/CT postvaccination pitfalls and presented superior tumor localization.

Radiochemical Synthesis and Evaluation of 3-[11C]Methyl-4-aminopyridine in Rodents and Nonhuman Primates for Imaging Potassium Channels in the CNS.

Demyelination, the loss of the insulating sheath of neurons, causes failed or slowed neuronal conduction and contributes to the neurological symptoms in multiple sclerosis, traumatic brain and spinal cord injuries, stroke, and dementia. In demyelinated neurons, the axonal potassium channels Kv1.1 and Kv1.2, generally under the myelin sheath, become exposed and upregulated. Therefore, imaging these channels using positron emission tomography can provide valuable information for disease diagnosis and monitoring. Here, we describe a novel tracer for Kv1 channels, [11C]3-methyl-4-aminopyridine ([11C]3Me4AP). [11C]3Me4AP was efficiently synthesized via Pd(0)-Cu(I) comediated Stille cross-coupling of a stannyl precursor containing a free amino group. Evaluation of its imaging properties in rats and nonhuman primates showed that [11C]3Me4AP has a moderate brain permeability and slow kinetics. Additional evaluation in monkeys showed that the tracer is metabolically stable and that a one-tissue compartment model can accurately model the regional brain time-activity curves. Compared to the related tracers [18F]3-fluoro-4-aminopyridine ([18F]3F4AP) and [11C]3-methoxy-4-aminopyridine ([11C]3MeO4AP), [11C]3Me4AP shows lower initial brain uptake, which indicates reduced permeability to the blood-brain barrier and slower kinetics, suggesting higher binding affinity consistent with in vitro studies. While the slow kinetics and strong binding affinity resulted in a tracer with less favorable properties for imaging the brain than its predecessors, these properties may make 3Me4AP useful as a therapeutic.

A near-infrared fluorescent long-chain fatty acid toward optical imaging of cardiac metabolism in living mice.

Non-invasive fatty acid (FA) metabolic imaging is crucial for the evaluation of cardiac function in the heart. Currently, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are widely employed for cardiac metabolic imaging both in pre-clinical and clinical studies. Although SPECT and PET enable highly sensitive cardiac metabolic imaging, there are several disadvantages such as the high cost of instruments and radioactive tracer synthesis. In contrast, near-infrared (NIR) optical imaging using fluorescent FAs provides a simple and useful platform for in vivo imaging of cardiac metabolism. In this work, we synthesized a NIR fluorescence labelled long-chain fatty acid (LCFA) for real-time imaging of cardiac metabolism in vivo. A NIR fluorescence labelled LCFA was designed as an analogue of ß-methyl [123I] iodophenyl-pentanedecanoic acid (123I-BMIPP), which is widely used for the diagnosis of heart diseases in clinical practice. As a NIR fluorescent label, we used an Alexa 680 fluorophore that emits over 700 nm. By conjugation of Alexa 680 to Amino-BMPP (15-(4-(3-aminopropyl)phenyl)-3-methylpentadecanoic acid), we prepared a NIR fluorescent BMIPP analogue, Alexa680-BMPP. NIR fluorescence imaging showed that Alexa680-BMPP is taken up by the mouse heart tissue after intravenous injection, showing that Alexa680-BMPP can act as a fluorescent LCFA analogue. Among Alexa680 conjugated FA analogues including short and middle chain NIR fluorescent FAs, Alexa680-BMPP was most efficiently taken up by heart tissues. For fasted and fed mice, the difference in the degree of the uptake of Alexa680-BMPP in their heart tissues was clearly observed by in vivo and ex vivo NIR fluorescence imaging. Herein, we present the synthesis of a NIR fluorescent LCFA, Alexa680-BMPP, and its capability for real-time optical imaging of cardiac metabolism in living mice.

Investigation of aqueous phase dynamics in a uranium stripping unit using radioactive tracer.

Mixer-setters units are widely used in uranium purification processes. For efficient operations of mixer-settler units, it is essential to measure the hydrodynamics parameters of the different phases involved. The residence time distribution (RTD) measurement is commonly used method to estimate the hydrodynamics parameters of process reactors. In the present study, RTD of the aqueous phase was measured in different stages mixer-settler unit (mixers, settlers and mixer-settler units) used for stripping operation using Iodine-131 as a radiotracer. For the RTD measurements, radiotracer was injected as an impulse in aqueous phase feed line and its movement was monitored at different locations in the stripping unit using NaI(Tl) detectors. The mean residence times (MRTs) of the aqueous phase were estimated from measured RTD curves. For quantification of the degree of mixing, suitable flow models were proposed based on design and nature of the measured RTD curves and subsequently used for simulation. Based on the results of the RTD study, the mixing of aqueous phase was characterized and design of the stripping unit and its sub-units were validated. The optimum conditions were identified for efficient for the operation of the stripping unit.

Aporte de la centellografía con trazadores tecneciados fosfatados al diagnóstico de amiloidosis cardíaca / Contribution of scintigraphy with technetium phosphated tracers to the diagnosis of cardiac amyloidosis / Contribuição da cintilografia com traçadores fosfatados com tecnécio para o diagnóstico de amiloidose cardíaca

Las amiloidosis son enfermedades causadas por el depósito patológico extracelular de un material proteico fibrilar e insoluble denominado amiloide, que puede estar vinculado a cadenas livianas (AL) o transtirretina (TTR). La amiloidosis cardíaca provoca una cardiomiopatía restrictiva de carácter progresivo caracterizada por falla cardíaca con función sistólica relativamente preservada, que se asocia a elevada mortalidad. Aunque el diagnóstico definitivo tradicionalmente se basa en la biopsia endomiocárdica, los avances en imagenología han mejorado su abordaje y la reciente introducción de terapias especificas permiten augurar cambios significativos en el pronóstico. El tratamiento difiere según el tipo de amiloide involucrado y su resultado depende de la instauración precoz de este, por lo cual resulta esencial un diagnóstico preciso y temprano. El centellograma cardíaco con fosfatos marcados (99mTc-PYP u otros), ampliamente disponible y de relativo bajo costo, se considera en la actualidad como una "biopsia molecular no invasiva" para el diagnóstico de la amiloidosis tipo ATTR, que debe ser usado en conjunto con la investigación de proteínas monoclonales en pacientes con sospecha clínica de la enfermedad.

Amyloidoses are diseases caused by the extracellular deposition of a fibrillar and insoluble protein material called amyloid, which can be linked either to light chains (AL) or transthyretin (TTR). Cardiac amyloidosis causes a progressive restrictive cardiomyopathy characterized by heart failure with relatively preserved systolic function, which is associated with high mortality. Although a definitive diagnosis is traditionally based on endomyocardial biopsy, advances in cardiac imaging have improved its approach, and the recent introduction of specific therapies predicts significant changes in prognosis. Since treatment differs according to the type of amyloid involved and the results depend on a prompt implementation, an accurate and early diagnosis is essential. Cardiac scintigraphy with labeled phosphates (99mTc-PYP or others), widely available and relatively inexpensive, is currently considered a "noninvasive molecular biopsy" for the diagnosis of ATTR type amyloidosis, which should be used in conjunction with investigation of monoclonal proteins in patients with clinical suspicion of the disease.

As amiloidoses são doenças causadas pela deposição patológica extracelular de um material proteico fibrilar e insolúvel, denominado amiloide, que pode estar ligado a cadeias leves (AL) ou transtirretina (TTR). A amiloidose cardíaca causa cardiomiopatia restritiva progressiva caracterizada por insuficiência cardíaca com função sistólica relativamente preservada, que está associada a alta mortalidade. Embora o diagnóstico definitivo seja tradicionalmente baseado na biópsia endomiocárdica, os avanços nos exames de imagem aprimoraram sua abordagem e a recente introdução de terapias específicas pode predizer mudanças significativas no prognóstico. O tratamento varia de acordo com o tipo de amiloide envolvida e seu resultado depende do início precoce, por isso um diagnóstico preciso e precoce é essencial. A cintilografia cardíaca com fosfatos marcados (99mTc-PYP ou outros), amplamente disponível e relativamente econômico, é atualmente considerada uma "biópsia molecular não invasiva" para o diagnóstico de amiloidose do tipo ATTR, que deve ser usada em conjunto com a investigação de proteínas monoclonais em pacientes com suspeita clínica da doença.

Stimuli-Responsive Macrocyclization Scaffold Allows In Situ Self-Assembly of Radioactive Tracers for Positron Emission Tomography Imaging of Enzyme Activity.

Target-enabled bioorthogonal reaction and self-assembly of a small-molecule probe into supramolecules have shown promise for molecular imaging. In this paper, we report a new stimuli-responsive bioorthogonal reaction scaffold (SF) for controlling in situ self-assembly by engineering the condensation reaction between 2-cyanobenzothiazole and cysteine. For probes with the SF scaffold, intramolecular cyclization took place soon after activation, which could efficiently outcompete free cysteine even at a low concentration and result in efficient aggregation in the target. Through integration with different enzyme-responsive substrates and an ammoniomethyl-trifluoroborate moiety (AmBF3), two radioactive positron emission tomography (PET) tracers, [18F]SF-DEVD and [18F]SF-Glu, were designed, which showed high stability under physiological conditions and could produce clear PET signal in tumors to detect enzyme activity (e.g., caspase-3, γ-glutamyltranspeptidase) timely and accurately. Our results demonstrated that the scaffold SF could serve as a general molecular scaffold in the development of smart PET tracers for noninvasive imaging of enzyme activity, which could contribute to tumor detection and treatment efficacy evaluation.