Delayed Graft Function After Kidney Transplantation: The Role of Residual Diuresis and Waste Products, as Oxalic Acid and Its Precursors.

Delayed graft function (DGF) after kidney transplantation heralds a worse prognosis. In patients with hyperoxaluria, the incidence of DGF is high. Oxalic acid is a waste product that accumulates when kidney function decreases.

Alloreactive T cells to Assess Acute Rejection Risk in Kidney Transplant Recipients.

Unlabelled: Memory T cells are important mediators of transplant rejection but are not routinely measured before or after kidney transplantation. The aims of this study were as follows: (1) validate whether pretransplant donor-reactive memory T cells are reliable predictors of acute rejection (AR) (2) determine whether donor-reactive memory T cells can distinguish AR from other causes of transplant dysfunction.

Methods: Samples from 103 consecutive kidney transplant recipients (2018-2019) were obtained pretransplantation and at time of for-cause biopsy sampling within 6 mo of transplantation.

Preclinical comparative study of [F]AlF-PSMA-11 and [F]PSMA-1007 in varying PSMA expressing tumors.

A wide variety of F-labeled PSMA-targeting PET radiotracers have been developed, including [F]AlF-PSMA-11. As there is only limited data on the comparison with other F-labeled PSMA PET tracers, a comparative preclinical study between [F]AlF-PSMA-11 and [F]PSMA-1007 was conducted. Mice with varying PSMA expressing tumors (C4-2, 22Rv1 and PC-3, each n = 5) underwent two PET/CT scans with both [F]AlF-PSMA-11 and [F]PSMA-1007.

Positron Emission Tomography-based Dose Painting Radiation Therapy in a Glioblastoma Rat Model using the Small Animal Radiation Research Platform.

A rat glioblastoma model to mimic chemo-radiation treatment of human glioblastoma in the clinic was previously established. Similar to the clinical treatment, computed tomography (CT) and magnetic resonance imaging (MRI) were combined during the treatment-planning process. Positron emission tomography (PET) imaging was subsequently added to implement sub-volume boosting using a micro-irradiation system.

Donor-Derived Cell-Free DNA for the Detection of Heart Allograft Injury: The Impact of the Timing of the Liquid Biopsy.

In heart transplant recipients, donor-derived cell-free DNA (ddcfDNA) is a potential biomarker for acute rejection (AR), in that increased values may indicate rejection. For the assessment of ddcfDNA as new biomarker for rejection, blood plasma sampling around the endomyocardial biopsy (EMB) seems a practical approach. To evaluate the effect of the EMB procedure on ddcfDNA values, ddcfDNA values before the EMB were pairwise compared to ddcfDNA values after the EMB.

Association Between the Intracellular Tacrolimus Concentration in CD3 + T Lymphocytes and CD14 + Monocytes and Acute Kidney Transplant Rejection.

Background: Intracellular tacrolimus concentration in peripheral blood mononuclear cells (PBMCs) (TAC [PBMC] ) has been proposed to better represent its active concentration than its whole blood concentration. As tacrolimus acts on T lymphocytes and other white blood cells, including monocytes, we investigated the association of tacrolimus concentration in CD3 + T lymphocytes (TAC [CD3] ) and CD14 + monocytes (TAC [CD14] ) with acute rejection after kidney transplantation.

Methods: From a total of 61 samples in this case-control study, 28 samples were obtained during biopsy-proven acute rejection (rejection group), and 33 samples were obtained in the absence of rejection (control group).

A Novel High-throughput Droplet Digital PCR-based Indel Quantification Method for the Detection of Circulating Donor-derived Cell-free DNA After Kidney Transplantation.

Background: Donor-derived cell-free DNA (ddcfDNA) is a promising minimally invasive biomarker for acute rejection (AR) in kidney transplant recipients. To assess the diagnostic value of ddcfDNA as a marker for AR, ddcfDNA was quantified at multiple time points after kidney transplantation with a novel high-throughput droplet digital PCR indel method that allowed for the absolute quantification of ddcfDNA.

Methods: In this study, ddcfDNA in plasma samples from 223 consecutive kidney transplant recipients was analyzed pretransplantation; at 3, 7, and 180 d after transplantation; and at time of for-cause biopsies obtained within the first 180 d after transplantation.

Recent advancements in F-labeled PSMA targeting PET radiopharmaceuticals.

Prostate specific membrane antigen (PSMA) is an attractive target for molecular imaging of prostate cancer and several other solid tumors because of its overexpression in prostate carcinoma and tumor neovasculature, respectively. While currently most commonly used PSMA PET radioligands are Ga-labeled compounds, the short half-life and relatively low available radioactivity of gallium-68 have led to a steep increase in the development of F-labeled PSMA ligands. Several F-PSMA tracers such as [F]DCFPyL and [F]PSMA-1007 are already established in clinical practice, but there are still several drawbacks to be considered.

Impact of the molar activity and PSMA expression level on [F]AlF-PSMA-11 uptake in prostate cancer.

This two-part preclinical study aims to evaluate prostate specific membrane antigen (PSMA) as a valuable target for expression-based imaging applications and to determine changes in target binding in function of varying apparent molar activities (MA) of [F]AlF-PSMA-11. For the evaluation of PSMA expression levels, male NOD/SCID mice bearing prostate cancer (PCa) xenografts of C4-2 (PSMA+++), 22Rv1 (PSMA+) and PC-3 (PSMA-) were administered [F]AlF-PSMA-11 with a medium MA (20.24 ± 3.

Comparison of In Vivo and Ex Vivo Magnetic Resonance Imaging in a Rat Model for Glioblastoma-Associated Epilepsy.

Magnetic resonance imaging (MRI) is frequently used for preclinical treatment monitoring in glioblastoma (GB). Discriminating between tumors and tumor-associated changes is challenging on in vivo MRI. In this study, we compared in vivo MRI scans with ex vivo MRI and histology to estimate more precisely the abnormal mass on in vivo MRI.

A perspective on the radiopharmaceutical requirements for imaging and therapy of glioblastoma.

Despite numerous clinical trials and pre-clinical developments, the treatment of glioblastoma (GB) remains a challenge. The current survival rate of GB averages one year, even with an optimal standard of care. However, the future promises efficient patient-tailored treatments, including targeted radionuclide therapy (TRT).

Circulating cell-free nucleosomes as biomarker for kidney transplant rejection: a pilot study.

Background: There is an unmet need for noninvasive markers specific for kidney transplant rejection. Such a marker may eventually overcome the need for a transplant biopsy. In this pilot study, the potential of circulating cell-free nucleosomes (CCFN) to serve as a biomarker for kidney transplant rejection was evaluated.

Intra-individual dynamic comparison of F-PSMA-11 and Ga-PSMA-11 in LNCaP xenograft bearing mice.

Recently, a F-labeled derivative of the widely used Ga-PSMA-11 was developed for PET imaging of prostate cancer. Although F-PSMA-11 has already been evaluated in a Phase I and Phase II clinical trial, preclinical evaluation of this radiotracer is important for further understanding its dynamic behavior. Saturation binding experiments were conducted by incubation of LNCaP cells with F-PSMA-11 or Ga-PSMA-11 for 1 h, followed by determination of the specific and aspecific binding.

Development of a Rat Model for Glioma-Related Epilepsy.

Seizures are common in patients with high-grade gliomas (30-60%) and approximately 15-30% of glioblastoma (GB) patients develop drug-resistant epilepsy. Reliable animal models are needed to develop adequate treatments for glioma-related epilepsy. Therefore, fifteen rats were inoculated with F98 GB cells (GB group) and four rats with vehicle only (control group) in the right entorhinal cortex.

Radiosynthesis, in vitro and preliminary biological evaluation of [ F]2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid, a novel alanine serine cysteine transporter 2 inhibitor-based positron emission tomography tracer.

The metabolic alterations in tumors make it possible to visualize the latter by means of positron emission tomography, enabling diagnosis and providing metabolic information. The alanine serine cysteine transporter-2 (ASCT-2) is the main transporter of glutamine and is upregulated in several tumors. Therefore, a good positron emission tracer targeting this transport protein would have substantial value.

Radiosynthesis, in vitro and preliminary in vivo evaluation of the novel glutamine derived PET tracers [F]fluorophenylglutamine and [F]fluorobiphenylglutamine.

Introduction: Glucose has been deemed the driving force of tumor growth for decades. However, research has shown that several tumors metabolically shift towards glutaminolysis. The development of radiolabeled glutamine derivatives could be a useful molecular imaging tool for visualizing these tumors.

2-[F]FELP, a novel LAT1-specific PET tracer, for the discrimination between glioblastoma, radiation necrosis and inflammation.

Introduction: Considering the need for rapid change of treatment in recurrent glioblastoma (GB), it is of utmost importance to characterize PET radiopharmaceuticals that allow early discrimination of tumor from therapy-related effects. In this study, we examined the value of 2-[F]FELP as a LAT1 tumor-specific PET tracer in comparison with [F]FDG and [F]FET in a combined orthotopic rat radiation necrosis and glioblastoma model. A second experiment compared 2-[F]FELP to [F]FDG in a mouse glioblastoma - inflammation model.

Kinetic analysis of [F] altanserin bolus injection in the canine brain using PET imaging.

Background: Currently, [F] altanserin is the most frequently used PET-radioligand for serotonin (5-HT) receptor imaging in the human brain but has never been validated in dogs. In vivo imaging of this receptor in the canine brain could improve diagnosis and therapy of several behavioural disorders in dogs. Furthermore, since dogs are considered as a valuable animal model for human psychiatric disorders, the ability to image this receptor in dogs could help to increase our understanding of the pathophysiology of these diseases.

Adjuvant therapeutic potential of tonabersat in the standard treatment of glioblastoma: A preclinical F98 glioblastoma rat model study.

Purpose: Even with an optimal treatment protocol, the median survival of glioblastoma (GB) patients is only 12-15 months. Hence, there is need for novel effective therapies that improve survival outcomes. Recent evidence suggests an important role for connexin (Cx) proteins (especially Cx43) in the microenvironment of malignant glioma.

Cost-Effectiveness of [F] Fluoroethyl-L-Tyrosine for Temozolomide Therapy Assessment in Patients With Glioblastoma.

Glioblastomas are the most aggressive of all gliomas. The prognosis of these gliomas, which are classified as grade IV tumors by the World Health Organization (WHO), is poor. Combination therapy, including surgery, radiotherapy, and chemotherapy has variable outcomes and is expensive.

Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment.

Background: In solid organ transplant (SOT) recipients, transplant rejection during immune checkpoint inhibitor (ICI) treatment for cancer is a clinical problem. Donor-derived cell-free DNA (dd-cfDNA) can be detected in blood and is a sensitive biomarker for diagnosis of acute rejection in SOT recipients. To our best knowledge, this is the first case report of a kidney transplant recipient with advanced cancer treated with ICI who was monitored with dd-cfDNA.

PET quantification of [18F]MPPF in the canine brain using blood input and reference tissue modelling.

Numerous studies have shown that the serotonin1A (5-HT1A) receptor is implicated in the pathophysiology and treatment of several psychiatric and neurological disorders. Furthermore, functional imaging studies in a variety of species have demonstrated that 4-(2´-Methoxyphenyl)-1-[2´-(N-2´´-pyridinyl)-p- [18F]fluorobenzamidoethylpiperazine ([18F]MPPF) is a valid and useful PET tracer to visualize the 5HT1A receptor. However, to our knowledge, [18F]MPPF has never been demonstrated in the canine brain.

Technical feasibility of [F]FET and [F]FAZA PET guided radiotherapy in a F98 glioblastoma rat model.

Background: Glioblastoma (GB) is the most common primary malignant brain tumor. Standard medical treatment consists of a maximal safe surgical resection, subsequently radiation therapy (RT) and chemotherapy with temozolomide (TMZ). An accurate definition of the tumor volume is of utmost importance for guiding RT.