Perfusion Showdown: Comparison of Multiple MRI Perfusion Techniques in the Grading of Pediatric Brain Tumors.

Background And Purpose: There are multiple MRI perfusion techniques, with limited available literature comparing these techniques in the grading of pediatric brain tumors. For efficiency and limiting scan time, ideally only one MRI perfusion technique can be used in initial imaging. We compared DSC, DCE, and IVIM along with ADC from DWI for differentiating high versus low grade pediatric brain tumors.

Comparing Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen-Positron Emission Tomography for Prediction of Extraprostatic Extension of Prostate Cancer and Surgical Guidance: A Prospective Nonrandomized Clinical Trial.

Purpose: Survivors of surgically managed prostate cancer may experience urinary incontinence and erectile dysfunction. Our aim was to determine if Ga-prostate-specific membrane antigen-11 positron emission tomography CT (PSMA-PET) in addition to multiparametric (mp) MRI scans improved surgical decision-making for nonnerve-sparing or nerve-sparing approach.

Materials And Methods: We prospectively enrolled 50 patients at risk for extraprostatic extension (EPE) who were scheduled for prostatectomy.

The 'bIUreactor': An Open-Source 3D Tissue Research Platform.

We developed the open-source bIUreactor research platform for studying 3D structured tissues. The versatile and modular platform allows a researcher to generate 3D tissues, culture them with oxygenated perfusion, and provide cyclic loading, all in their own lab (in laboratorium) for an all in cost of $8,000 including 3D printer, printing resin, and electronics. We achieved this by applying a design philosophy that leverages 3D printing, open-source software and hardware, and practical techniques to produce the following: 1.

A Comparison of Arterial Input Function Interpolation Methods for Patlak Plot Analysis of Ga-PSMA-11 PET Prostate Cancer Studies.

Positron emission tomography (PET) imaging enables quantitative assessment of tissue physiology. Dynamic pharmacokinetic analysis of PET images requires accurate estimation of the radiotracer plasma input function to derive meaningful parameter estimates, and small discrepancies in parameter estimation can mimic subtle physiologic tissue variation. This study evaluates the impact of input function interpolation method on the accuracy of Patlak kinetic parameter estimation through simulations modeling the pharmacokinetic properties of [68Ga]-PSMA-11.

Comparison of tracer kinetic models for Ga-PSMA-11 PET in intermediate-risk primary prostate cancer patients.

Background: Ga-PSMA-11 positron emission tomography enables the detection of primary, recurrent, and metastatic prostate cancer. Regional radiopharmaceutical uptake is generally evaluated in static images and quantified as standard uptake values (SUVs) for clinical decision-making. However, analysis of dynamic images characterizing both tracer uptake and pharmacokinetics may offer added insights into the underlying tissue pathophysiology.

Comparison of Tracer Kinetic Models for 68Ga-PSMA-11 PET in Intermediate Risk Primary Prostate Cancer Patients.

Background: Ga-PSMA-11 positron emission tomography enables the detection of primary, recurrent, and metastatic prostate cancer. Regional radiopharmaceutical uptake is generally evaluated in static images and quantified as standard uptake values (SUV) for clinical decision-making. However, analysis of dynamic images characterizing both tracer uptake and pharmacokinetics may offer added insights into the underlying tissue pathophysiology.

Hybrid F-Fluoroethyltyrosine PET and MRI with Perfusion to Distinguish Disease Progression from Treatment-Related Change in Malignant Brain Tumors: The Quest to Beat the Toughest Cases.

Conventional MRI has important limitations when assessing for progression of disease (POD) versus treatment-related changes (TRC) in patients with malignant brain tumors. We describe the observed impact and pitfalls of implementing F-fluoroethyltyrosine (F-FET) perfusion PET/MRI into routine clinical practice. Through expanded-access investigational new drug use of F-FET, hybrid F-FET perfusion PET/MRI was performed during clinical management of 80 patients with World Health Organization central nervous system grade 3 or 4 gliomas or brain metastases of 6 tissue origins for which the prior brain MRI results were ambiguous.

Use of multimodality imaging, histology, and treatment feasibility to characterize a transgenic -null rat model of glioblastoma.

Many drugs that show potential in animal models of glioblastoma (GBM) fail to translate to the clinic, contributing to a paucity of new therapeutic options. In addition, animal model development often includes histologic assessment, but multiparametric/multimodality imaging is rarely included despite increasing utilization in patient cancer management. This study developed an intracranial recurrent, drug-resistant, human-derived glioblastoma tumor in Sprague-Dawley - knockout rat and was characterized both histologically and using multiparametric/multimodality neuroimaging.

Assessing extra-prostatic extension for surgical guidance in prostate cancer: Comparing two PSMA-PET tracers with the standard-of-care.

Background: Incontinence and impotence occur following radical prostatectomy due to injury to nerves and sphincter muscle. Preserving nerves and muscle adjacent to prostate cancer risks positive surgical margins. Advanced imaging with MRI has improved cancer localization but limitations exist.

In Vivo Quantitative Whole-Body Perfusion Imaging Using Radiolabeled Copper(II) Bis(Thiosemicarbazone) Complexes and Positron Emission Tomography (PET).

Traditional quantitative perfusion imaging methods require complex data acquisition and analysis strategies; typically require ancillary arterial blood sampling for measurement of input functions; are limited to single organ or tissue regions in an imaging session; and because of their complexity, are not well suited for routine clinical implementation in a standardized fashion that can be readily repeated across diverse clinical sites. The whole-body perfusion method described in this chapter has the advantages of on-demand radiotracer production; simple tissue pharmacokinetics enabling standardized estimation of perfusion; short-lived radionuclides, facilitating repeat or combination imaging procedures; and scalability to support widespread clinical implementation. This method leverages the unique physiological characteristics of radiolabeled copper(II) bis(thiosemicarbazone) complexes and the detection sensitivity of positron emission tomography (PET) to produce quantitatively accurate whole-body perfusion images.

The Brain: Is it a Next Frontier to Better Understand the Regulation and Control of Hematopoiesis for Future Modulation and Treatment?

We wish to suggest the possibility there is a link between the brain and hematopoiesis in the bone marrow and that in the future it may be possible to use such information for better understanding of the regulation of hematopoiesis, and for efficacious treatment of hematopoietic disorders.

Advanced imaging techniques for neuro-oncologic tumor diagnosis, with an emphasis on PET-MRI imaging of malignant brain tumors.

Purpose Of Review: This review will explore the latest in advanced imaging techniques, with a focus on the complementary nature of multiparametric, multimodality imaging using magnetic resonance imaging (MRI) and positron emission tomography (PET).

Recent Findings: Advanced MRI techniques including perfusion-weighted imaging (PWI), MR spectroscopy (MRS), diffusion-weighted imaging (DWI), and MR chemical exchange saturation transfer (CEST) offer significant advantages over conventional MR imaging when evaluating tumor extent, predicting grade, and assessing treatment response. PET performed in addition to advanced MRI provides complementary information regarding tumor metabolic properties, particularly when performed simultaneously.

Prostate Specific Membrane Antigen Targeted Positron Emission Tomography of Primary Prostate Cancer: Assessing Accuracy with Whole Mount Pathology.

Purpose: We evaluated which lesions are detected and missed on [Ga]Ga-PSMA (prostate specific membrane antigen)-11 positron emission tomography in patients with primary prostate cancer.

Materials And Methods: Patients undergoing radical prostatectomy were enrolled in this prospective observational study. Patients underwent [Ga]Ga-PSMA-11 positron emission tomography/computerized tomography or positron emission tomography/magnetic resonance imaging prior to surgery and received a dose of [Ga]Ga-PSMA-11 intraoperatively for positron emission tomography of extirpated specimens.

[Ga]Ga-P16-093 as a PSMA-Targeted PET Radiopharmaceutical for Detection of Cancer: Initial Evaluation and Comparison with [Ga]Ga-PSMA-11 in Prostate Cancer Patients Presenting with Biochemical Recurrence.

Purpose: This study was undertaken to evaluate radiation dosimetry for the prostate-specific membrane antigen targeted [Ga]Ga-P16-093 radiopharmaceutical, and to initially assess agent performance in positron emission tomography (PET) detection of the site of disease in prostate cancer patients presenting with biochemical recurrence.

Procedures: Under IND 133,222 and an IRB-approved research protocol, we evaluated the biodistribution and pharmacokinetics of [Ga]Ga-P16-093 with serial PET imaging following intravenous administration to ten prostate cancer patients with biochemical recurrence. The recruited subjects were all patients in whom a recent [Ga]Ga-PSMA-11 PET/X-ray computed tomography (CT) exam had been independently performed under IND 131,806 to assist in decision-making with regard to their clinical care.

Synthesis and in vitro biological evaluation of new P2X7R radioligands [C]halo-GSK1482160 analogs.

The reference standards halo-GSK1482160 (F-, Br-, and I-) and their corresponding precursors desmethyl-halo-GSK1482160 (F-, Br-, and I-) were synthesized from (S)-1-methyl-5-oxopyrrolidine-2-carboxylic acid or (S)-5-oxopyrrolidine-2-carboxylic acid and 2-halo-3-(trifluoromethyl)benzylamine (F-, Br-, and I-) in one step with 45-93% yields. The target tracers [C]halo-GSK1482160 (F-, Br-, and I-) were prepared from desmethyl-halo-GSK1482160 (F-, Br-, and I-) with [C]CHOTf under basic conditions (NaOH-NaCO, solid, w/w 1:2) through N-[C]methylation and isolated by HPLC combined with SPE in 40-50% decay corrected radiochemical yield. The radiochemical purity was >99%, and the molar activity (A) at end of bombardment (EOB) was 370-740 GBq/μmol.

Synthesis and initial in vitro characterization of a new P2X7R radioligand [F]IUR-1602.

The overexpression of P2X7R is associated with neuroinflammation and plays an important role in various neurodegenerative diseases. The [F]fluoropropyl derivative of GSK1482160, [F]IUR-1602, has been first prepared and examined as a new potential P2X7R radioligand. The reference standard IUR-1602 was synthesized from tert-butyl (S)-5-oxopyrrolidine-2-carboxylate, fluoropropylbromide, and 2-chloro-3-(trifluoromethyl)benzylamine with overall chemical yield 13% in three steps.

Combination GLP-1 and Insulin Treatment Fails to Alter Myocardial Fuel Selection vs. Insulin Alone in Type 2 Diabetes.

Context: It is unclear if effects of glucagon-like peptide-1 (GLP-1) and clinically available GLP-1 agonists on the heart occur at clinical doses in humans, possibly contributing to reduced cardiovascular disease risk.

Objective: To determine whether liraglutide, at clinical dosing, augments myocardial glucose uptake (MGU) alone or combined with insulin compared with insulin alone in metformin-treated type 2 diabetes mellitus (T2D).

Design: In a randomized clinical trial of patients with T2D treated with metformin plus oral agents or basal insulin, myocardial fuel use was compared after 3 months of treatment with insulin detemir, liraglutide, or combination detemir plus liraglutide added to background metformin.

Synthesis and preliminary biological evaluation of a novel P2X7R radioligand [F]IUR-1601.

The reference standard IUR-1601 ((S)-N-(2-chloro-3-(trifluoromethyl)benzyl)-1-(2-fluoroethyl)-5-oxopyrrolidine-2-carboxamide) was synthesized from tert-butyl (S)-5-oxopyrrolidine-2-carboxylate, fluoroethylbromide, and 2-chloro-3-(trifluoromethyl)benzylamine with overall chemical yield 12% in three steps. The target tracer [F]IUR-1601 ((S)-N-(2-chloro-3-(trifluoromethyl)benzyl)-1-(2-[F]fluoroethyl)-5-oxopyrrolidine-2-carboxamide) was synthesized from desmethyl-GSK1482160 with 2-[F]fluoroethyl tosylate, prepared from 1,2-ethylene glycol-bis-tosylate and K[F]F/Kryptofix2.2.

Olfactory identification in subjective cognitive decline and mild cognitive impairment: Association with tau but not amyloid positron emission tomography.

Introduction: We investigated the association between olfactory identification and Alzheimer's disease biomarkers, including amyloid, tau, and neurodegeneration.

Methods: Thirty-four older adults, including 19 cognitively normal (CN), 10 subjective cognitive decline (SCD), and 5 mild cognitive impairment, underwent amyloid positron emission tomography, magnetic resonance imaging, and the University of Pennsylvania Smell Identification Test (UPSIT). Twenty-six also underwent tau positron emission tomography.

Effects of combination treatment with alendronate and raloxifene on skeletal properties in a beagle dog model.

A growing number of studies have investigated combination treatment as an approach to treat bone disease. The goal of this study was to investigate the combination of alendronate and raloxifene with a particular focus on mechanical properties. To achieve this goal we utilized a large animal model, the beagle dog, used previously by our laboratory to study both alendronate and raloxifene monotherapies.

Synthesis and preliminary biological evaluation of radiolabeled 5-BDBD analogs as new candidate PET radioligands for P2X4 receptor.

P2X4 receptor has become an interesting molecular target for treatment and PET imaging of neuroinflammation and associated brain diseases such as Alzheimer's disease. This study reports the first design, synthesis, radiolabeling and biological evaluation of new candidate PET P2X4 receptor radioligands using 5-BDBD, a specific P2X4 receptor antagonist, as a scaffold. 5-(3-Hydroxyphenyl)-1-[C]methyl-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one (N-[C]Me-5-BDBD analog, [C]9) and 5-(3-Bromophenyl)-1-[C]methyl-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one (N-[C]Me-5-BDBD, [C]8c) were prepared from their corresponding desmethylated precursors with [C]CHOTf through N-[C]methylation and isolated by HPLC combined with SPE in 30-50% decay corrected radiochemical yields with 370-1110GBq/µmol specific activity at EOB.

Synthesis and preliminary biological evaluation of [C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate for the fractalkine receptor (CXCR1).

The reference standard methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate (5) and its precursor 2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucine (6) were synthesized from 6-amino-2-mercaptopyrimidin-4-ol and BnBr with overall chemical yield 7% in five steps and 4% in six steps, respectively. The target tracer [C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate ([C]5) was prepared from the acid precursor with [C]CHOTf through O-[C]methylation and isolated by HPLC combined with SPE in 40-50% radiochemical yield, based on [C]CO and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370-1110GBq/μmol with a total synthesis time of ∼40-min from EOB.

Development of a novel magnetic resonance imaging acquisition and analysis workflow for the quantification of shock wave lithotripsy-induced renal hemorrhagic injury.

The current accepted standard for quantifying shock wave lithotripsy (SWL)-induced tissue damage is based on morphometric detection of renal hemorrhage in serial tissue sections from fixed kidneys. This methodology is time and labor intensive and is tissue destructive. We have developed a non-destructive magnetic resonance imaging (MRI) method that permits rapid assessment of SWL-induced hemorrhagic lesion volumes in post-mortem kidneys using native tissue contrast to reduce cycle time.

Estimation of radiation dosimetry for Ga-HBED-CC (PSMA-11) in patients with suspected recurrence of prostate cancer.

Introduction: This study was performed to estimate the human radiation dosimetry for [Ga]Ga-HBED-CC (PSMA-11) (Ga PSMA-11).

Methods: Under an RDRC-approved research protocol, we evaluated the biodistribution and pharmacokinetics of Ga PSMA-11 with serial PET imaging following intravenous administration to nine prostate cancer patients in whom clinical [C]acetate PET/CT exams had been independently performed under Expanded Access IND 118,204. List-mode imaging was performed over the initial 0-10min post-injection with the pelvis in the field-of-view.

Measurement of cardiovascular function using a novel view-sharing PET reconstruction method and tracer kinetic analysis.

Recent advancements in PET instrumentation have made the non-invasive assessment of cardiovascular function in small animals a reality. The majority of small animal PET systems use stationary detector gantries, thus affording high temporal resolution imaging of cardiac function. Systems designed to maximize spatial resolution and detection sensitivity employing rotating gantry designs are suboptimal when high temporal resolution imaging is needed.