Association of in vivo retention of [18f] flortaucipir pet with tau neuropathology in corresponding brain regions.

[18F]Flortaucipir is an FDA-approved tau-PET tracer that is increasingly utilized in clinical settings for the diagnosis of Alzheimer's disease. Still, a large-scale comparison of the in vivo PET uptake to quantitative post-mortem tau pathology and to other co-pathologies is lacking. Here, we examined the correlation between in vivo [18F]flortaucipir PET uptake and quantitative post-mortem tau pathology in corresponding brain regions from the AVID A16 end-of-life study (n = 63). All participants underwent [18F]flortaucipir PET scans prior to death, followed by a detailed post-mortem neuropathological examination using AT8 (tau) immunohistochemistry. Correlations between [18F]flortaucipir standardized uptake value ratios (SUVRs) and AT8 immunohistochemistry were assessed across 18 regions-of-interest (ROIs). To assess [18F]flortaucipir specificity and level of detection for tau pathology, correlations between [18F]flortaucipir SUVR and neuritic plaque score and TDP-43 stage were also computed and retention was further assessed in individuals with possible primary age-related tauopathy (PART), defined as Thal phase ≤ 2 and Braak stage I-IV. We found modest-to-strong correlations between in vivo [18F]flortaucipir SUVR and post-mortem tau pathology density in corresponding brain regions in all neocortical regions analyzed (rho-range = 0.61-0.79, p < 0.0001 for all). The detection threshold of [18F]flortaucipir PET was determined to be 0.85% of surface area affected by tau pathology in a temporal meta-ROI, and 0.15% in a larger cortical meta-ROI. No significant associations were found between [18F]flortaucipir SUVRs and post-mortem tau pathology in individuals with possible PART. Further, there was no correlation observed between [18F]flortaucipir and level of amyloid-ß neuritic plaque load (rho-range = - 0.16-0.12; p = 0.48-0.61) or TDP-43 stage (rho-range = - 0.10 to - 0.30; p = 0.18-0.65). In conclusion, our in vivo vs post-mortem study shows that the in vivo [18F]flortaucipir PET signal primarily reflects tau pathology, also at relatively low densities of tau proteinopathy, and does not bind substantially to tau neurites in neuritic plaques or in individuals with PART.

Difluoromethoxide Is a Strong Leaving Group in the Photoredox Deoxyradiofluorination of 2-Phenylpyridines.

A 2-phenyl-3-difluoromethoxy-pyridinyl moiety features in potent phosphodiesterase 4D inhibitors that are considered to be candidate radiotracers for positron emission tomography if they are labeled with fluorine-18. Fluorine-18 could be installed as desired at the 3'-phenyl position with acridinium-mediated photoredox radiodeoxyfluorination in homologues bearing variously substituted 3'-aryloxy groups. However, a distal 3-difluoromethoxide (-OCHF2) group strongly competes as a leaving group, especially when an electron-deficient aryloxy group is present at position 3'. A yield of up to 50% may occur without observable 19F for 18F exchange.

Cyclohexanediamine Triazole (CHDT) Functionalization Enables Labeling of Target Molecules with Al18F/68Ga/111In.

The Al18F-labeling approach offers a one-step access to radiofluorinated biomolecules by mimicking the labeling process for radiometals. Although these labeling conditions are considered to be mild compared to classic radiofluorinations, improvements of the chelating units have led to the discovery of (±)-H3RESCA, which allows Al18F-labeling already at ambient temperature. While the suitability of (±)-H3RESCA for functionalization and radiofluorination of proteins is well established, its use for small molecules or peptides is less explored. Herein, we advanced this acyclic pentadentate ligand by introducing an alkyne moiety for the late-stage functionalization of biomolecules via click chemistry. We show that in addition to Al18F-labeling, the cyclohexanediamine triazole (CHDT) moiety allows stable complexation of 68Ga and 111In. Three novel CHDT-functionalized PSMA inhibitors were synthesized and their Al18F-, 68Ga-, and 111In-labeled analogs were subjected to a detailed in vitro radiopharmacological characterization. Stability studies in vitro in human serum revealed among others a high kinetic inertness of all radiometal complexes. Furthermore, the Al18F-labeled PSMA ligands were characterized for their biodistribution in a LNCaP derived tumor xenograft mouse model by PET imaging. One radioligand, Al[18F]F-CHDT-PSMA-1, bearing a small azidoacetyl linker at the glutamate-urea-lysine motif, provided an in vivo performance comparable to that of [18F]PSMA-1007 but with even higher tumor-to-blood and tumor-to-muscle ratios at 120 min p.i. Overall, our results highlight the suitability of the novel CHDT moiety for functionalization and radiolabeling of small molecules or peptides with Al18F, 68Ga, and 111In and the triazole ring seems to entail favorable pharmacokinetic properties for molecular imaging purposes.

Preparation and Preclinical Evaluation of 18F-Labeled Olutasidenib Derivatives for Non-Invasive Detection of Mutated Isocitrate Dehydrogenase 1 (mIDH1).

Mutations of isocitrate dehydrogenase 1 (IDH1) are key biomarkers for glioma classification, but current methods for detection of mutated IDH1 (mIDH1) require invasive tissue sampling and cannot be used for longitudinal studies. Positron emission tomography (PET) imaging with mIDH1-selective radioligands is a promising alternative approach that could enable non-invasive assessment of the IDH status. In the present work, we developed efficient protocols for the preparation of four 18F-labeled derivatives of the mIDH1-selective inhibitor olutasidenib. All four probes were characterized by cellular uptake studies with U87 glioma cells harboring a heterozygous IDH1 mutation (U87-mIDH) and the corresponding wildtype cells (U87-WT). In addition, the most promising probe was evaluated by PET imaging in healthy mice and mice bearing subcutaneous U87-mIDH and U87-WT tumors. Although all four probes inhibited mIDH1 with variable potencies, only one of them ([18F]mIDH-138) showed significantly higher in vitro uptake into U87-mIDH compared to U87-WT cells. In addition, PET imaging with [18F]mIDH-138 in mice demonstrated good in vivo stability and low non-specific uptake of the probe, but also revealed significantly higher uptake into U87-WT compared to U87-mIDH tumors. Finally, application of a two-tissue compartment model (2TCM) to the PET data indicated that preferential tracer uptake into U87-WT tumors results from higher specific binding rather than from differences in tracer perfusion. In conclusion, these results corroborate recent findings that mIDH1-selective inhibition may not directly correlate with mIDH1-selective target engagement and indicate that in vivo engagement of wildtype and mutated IDH1 may be governed by factors that are not faithfully reproduced by in vitro assays, both of which could complicate development of PET probes.

Synthetic Efforts toward the Synthesis of a Fluorinated Analog of 5-Aminolevulinic Acid: Practical Synthesis of Racemic and Enantiomerically Defined 3-Fluoro-5-aminolevulinic Acid.

In 2017, the FDA authorized 5-aminolevulinic acid (5-ALA) for intraoperative optical imaging of suspected high-grade gliomas. This was the first authorized optical imaging agent for brain tumor surgery to enhance the visualization of malignant tissue. Herein we report the synthesis of a racemic and enantiopure fluorinated analog of 5-ALA, i.e., 3-fluoro-5-aminolevulinic acid (3F-5-ALA). We anticipate that these studies will provide the foundation for the future construction of a fluorine-18-labeled 5-ALA PET tracer to be used for functional and metabolic imaging of gliomas.

Sortase-Mediated Site-Specific Conjugation to Prepare Fluorine-18-Labeled Nanobodies.

Single-domain antibodies, or nanobodies (Nbs), are promising biomolecules for use in molecular imaging due to their excellent affinity, specificity, and fast clearance from the blood. Given their short blood half-life, pairing Nbs with short-lived imaging radioisotopes is desirable. Because fluorine-18 (18F) is routinely used for clinical imaging, it is an attractive radioisotope for Nbs. We report a novel sortase-based, site-specific 18F-labeling method applied to three nanobodies. Labeled nanobodies were synthesized either by a two-step indirect radiolabeling method in one pot or by a one-step direct labeling method using a sortase-mediated conjugation of either the radiolabeled chelator (H-GGGK((±)-Al[18F]FH3RESCA)-NH2) or the unlabeled chelator (H-GGGK((±)-H3RESCA)-NH2) followed by labeling with Al[18F]F, respectively. The overall radiochemical yields were 15-43% (n = 22, decay-corrected) in 70 min (indirect labeling) and 23-58% (n = 12, decay-corrected) in 50 min (direct labeling). The radiochemical purities of the labeled nanobodies prepared by both methods were >98% with a specific activity of 400-600 Ci/mmol (n = 22) for each of the three Nbs tested and exhibited excellent stability profiles under physiological conditions. This simple, site-specific, reproducible, and generalizable 18F-labeling method to prepare nanobodies (Nb-Al[18F]F-RESCA) or other low molecular weight biomolecules can easily be adopted in various settings for preclinical and clinical studies.

A nitroreductase responsive probe for early diagnosis of pulmonary fibrosis disease.

Idiopathic pulmonary fibrosis (IPF) is a serious interstitial lung disease. However, the definitive diagnosis of IPF is impeded by the limited capabilities of current diagnostic methods, which may fail to capture the optimal timing for treatment. The main goal of this study is to determine the feasibility of a nitroreductase (NTR) responsive probe, 18F-NCRP, for early detection and deterioration monitoring of IPF. 18F-NCRP was obtained with high radiochemical purity (>95 %). BLM-injured mice were established by intratracheal instillation with bleomycin (BLM) and characterized through histological analysis. Longitudinal PET/CT imaging, biodistribution study and in vitro autoradiography were performed. The correlations between the uptake of 18F-NCRP and mean lung density (tested by CT), as well as histopathological characteristics were analyzed. In PET imaging study, 18F-NCRP exhibited promising efficacy in monitoring the progression of IPF, which was earlier than CT. The ratio of uptake in BLM-injured lung to control lung increased from 1.4-fold on D15 to 2.2-fold on D22. Biodistribution data showed a significant lung uptake of 18F-NCRP in BLM-injured mice. There was a strong positive correlation between the 18F-NCRP uptake in the BLM-injured lungs and the histopathological characteristics. Given that, 18F-NCRP PET imaging of NTR, a promising biomarker for investigating the underlying pathogenic mechanism of IPF, is attainable as well as desirable, which might lay the foundation for establishing an NTR-targeted imaging evaluation system of IPF.

Evaluation of a novel PET tracer [18F]-Florbetazine for Alzheimer's disease diagnosis and ß-amyloid deposition quantification.

[18F]-Florbetazine ([18F]-92) is a selective PET tracer for ß-amyloid (Aß) depositions with a novel diaryl-azine scaffold to reduce lipophilicity and to achieve higher gray-to-white matter contrast. We aimed to assess its diagnostic value in Alzheimer's disease (AD) and pharmacokinetics characteristics in human subjects. METHODS: Six healthy controls (HCs) and nine AD patients underwent dynamic PET examination with [18F]-Florbetazine and a structural MRI scan. The time-activity-curves (TACs) for volumes of interest (VOIs) in cerebral cortex, cerebellar cortex and cerebral white matter was depicted and their standardized uptake value ratios (SUVRs) with cerebellar cortex as reference were compared between HCs and AD patients. The cerebral gray-to-white matter SUV ratio (GWR) was also calculated. RESULTS: In HCs, radioactivities in the cerebral cortex VOIs were homogeneously low and at the same level as in cerebellar cortex, while in AD patients, cortical VOIs expected to contain Aß exhibited high radioactivity. Cerebral cortex SUVRs remain relatively low in HCs while keep increasing along with time in AD patients. After 15 min, the cerebral cortex SUVRs became significant higher in AD patients compared to HCs with 100 % discrimination accuracy. In AD patients, GWR remained over 1.3 for all time intervals and visual inspection showed lower uptake in cerebral white matter compared to cerebral cortex. CONCLUSION: [18F]-Florbetazine PET showed high uptake on Aß plaques and high gray-to-white contrast in AD patients that are favorable in visual read. [18F]-Florbetazine can be potentially used for detection and quantification of Aß depositions in the living human brain.

Primary Prostatic Stromal Sarcoma on 18 F-PSMA PET/CT.

ABSTRACT: Primary prostatic stromal sarcoma is extremely rare. Serum PSA is usually normal. Here, we report a case of primary prostatic stromal sarcoma in a 23-year-old man. 18 F-prostate-specific membrane antigen (PSMA) PET/CT showed prostate mass and multiple low-density lesions in the liver with high PSMA expression. However, after chemotherapy, the level of PSMA expression in the prostate mass decreased, and PSMA expression lesions in the liver disappeared.

Interobserver and intraobserver agreement in PET/CT with [18F]DCFPyL according to TNM molecular and PSMA-RADS 2.0 criteria.

PURPOSE: The aim of this study was to determine the agreement between three observers with different levels of experience using the PSMA-RADS 2.0 criteria and the miTNM system for the interpretation of PET-PSMA with [18F]DCFPyL in males with prostate cancer. MATERIALS AND METHODS: PET-PSMA images from 114 prostate cancer patients were blindly reported twice by three different observers at intervals of 8 weeks. The evaluations were performed according to the molecular imaging TNM (miTNM) and PSMA-RADS 2.0 criteria. We used Fleiss' Kappa to analyse inter and intraobserver agreements. RESULTS: Moderate overall agreement was obtained in the assessment of the PET-PSMA results (Fleiss'k = 0.53; 95% CI 0.45-0.62; p < 0.001), with significant agreement in the miT, miN and miM reports. There was a substantial level of agreement in the reporting of prostatic disease and lymphatic involvement (Fleiss'k = 0.66 and 0.65), being lower than that observed in the reporting of metastatic disease (Fleiss'k = 0.86), especially in the M0 group (Fleiss'k = 0.99). Upon re-evaluation of the images, observer 1 had moderate overall agreement for miT (Fleiss'k = 0.51) and substantial agreement for miN and miM (Fleiss'k 0.75 and 0.63, respectively). CONCLUSIONS: The use of a structured scoring system such as PSMA-RADS 2.0, as well as the miTNM classification system in the interpretation of PET-PSMA images in prostate cancer patients, provides a highly reproducible report format. High levels of interobserver and intraobserver agreement are found, especially when ruling out disease, which supports its use in routine clinical practice.

[18F]RS-127445 radiosynthesis and evaluation as a 5-HT2B receptor PET radiotracer in rat brain.

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter involved in many physiological and pathological mechanisms through its numerous receptors. Among these, the 5-HT2B receptor is known to play a key role in multiple brain disorders but remains poorly understood. Positron emission tomography (PET) can contribute to a better understanding of pathophysiological mechanisms regulated by the 5-HT2B receptor. To develop the first PET radiotracer for the 5-HT2B receptor, RS-127445, a well-known 5-HT2B receptor antagonist, was labeled with fluorine-18. [18F]RS-127445 was synthesized in a high radiochemical purity and with a good molar activity and radiochemical yield. Preliminary PET scans in rats showed good brain penetration of [18F]RS-127445. However, competition experiments and in vitro autoradiography showed high non-specific binding, especially to brain white matter.

(SiFA)SeFe: A Hydrophilic Silicon-Based Fluoride Acceptor Enabling Versatile Peptidic Radiohybrid Tracers.

The radiohybrid (rh) concept to design targeted (and chemically identical) radiotracers for imaging or radionuclide therapy of tumors has gained momentum. For this strategy, a new bifunctional Silicon-based Fluoride Acceptor (SiFA) moiety (SiFA)SeFe was synthesized, endowed with improved hydrophilicity and high versatility of integration into rh-compounds. Preliminary radiolabeling and stability studies under different conditions were conducted using model bioconjugate peptides. Further, three somatostatin receptor 2 (sstR2)-targeted rh-compounds ((SiFA)SeFe-rhTATE1-3, TATE = (Tyr3)-octreotate) were developed. Compound (SiFA)SeFe-rhTATE3, enables labeling with 18F for PET imaging or chelation of 177Lu for therapy. The rh-compounds possess comparable receptor binding affinity and in vitro performance as good as the clinically proven gold standards. SstR2-specificity was further shown for (SiFA)SeFe-rhTATE2 using the chicken chorioallantoic membrane (CAM) model. The biodistribution of two compounds in mice showed high accumulation in tumors and excretion via the kidneys, demonstrating the clinical applicability of the (SiFA)SeFe moiety.

The impact of multicentric datasets for the automated tumor delineation in primary prostate cancer using convolutional neural networks on 18F-PSMA-1007 PET.

PURPOSE: Convolutional Neural Networks (CNNs) have emerged as transformative tools in the field of radiation oncology, significantly advancing the precision of contouring practices. However, the adaptability of these algorithms across diverse scanners, institutions, and imaging protocols remains a considerable obstacle. This study aims to investigate the effects of incorporating institution-specific datasets into the training regimen of CNNs to assess their generalization ability in real-world clinical environments. Focusing on a data-centric analysis, the influence of varying multi- and single center training approaches on algorithm performance is conducted. METHODS: nnU-Net is trained using a dataset comprising 161 18F-PSMA-1007 PET images collected from four distinct institutions (Freiburg: n = 96, Munich: n = 19, Cyprus: n = 32, Dresden: n = 14). The dataset is partitioned such that data from each center are systematically excluded from training and used solely for testing to assess the model's generalizability and adaptability to data from unfamiliar sources. Performance is compared through a 5-Fold Cross-Validation, providing a detailed comparison between models trained on datasets from single centers to those trained on aggregated multi-center datasets. Dice Similarity Score, Hausdorff distance and volumetric analysis are used as primary evaluation metrics. RESULTS: The mixed training approach yielded a median DSC of 0.76 (IQR: 0.64-0.84) in a five-fold cross-validation, showing no significant differences (p = 0.18) compared to models trained with data exclusion from each center, which performed with a median DSC of 0.74 (IQR: 0.56-0.86). Significant performance improvements regarding multi-center training were observed for the Dresden cohort (multi-center median DSC 0.71, IQR: 0.58-0.80 vs. single-center 0.68, IQR: 0.50-0.80, p < 0.001) and Cyprus cohort (multi-center 0.74, IQR: 0.62-0.83 vs. single-center 0.72, IQR: 0.54-0.82, p < 0.01). While Munich and Freiburg also showed performance improvements with multi-center training, results showed no statistical significance (Munich: multi-center DSC 0.74, IQR: 0.60-0.80 vs. single-center 0.72, IQR: 0.59-0.82, p > 0.05; Freiburg: multi-center 0.78, IQR: 0.53-0.87 vs. single-center 0.71, IQR: 0.53-0.83, p = 0.23). CONCLUSION: CNNs trained for auto contouring intraprostatic GTV in 18F-PSMA-1007 PET on a diverse dataset from multiple centers mostly generalize well to unseen data from other centers. Training on a multicentric dataset can improve performance compared to training exclusively with a single-center dataset regarding intraprostatic 18F-PSMA-1007 PET GTV segmentation. The segmentation performance of the same CNN can vary depending on the dataset employed for training and testing.

COVID-19 pneumonia incidentally discovered on [18F]F-PSMA-1007 PET/CT scan.

A 75-year-old man underwent a positron emission tomography/computed tomography (PET/CT) scan with fluorine-18-prostate specific membrane antigen ([¹8F]F-PSMA-1007) for initial staging of prostate adenocarcinoma. The scan showed lung infiltrates predominantly in both lower lobes with moderate uptake, in addition to a bilateral pulmonary hilar lymph node uptake. CT images revealed ground-glass opacities and a reticular pattern, suggesting COVID-19 pneumonia, which was confirmed by reverse transcription polymerase chain reaction (RT-PCR). Similar incidental findings have been reported in patients undergoing PET/CT scans with other radiotracers. In this case, the probable lung angiogenesis linked to COVID-19 infection can be potencially demonstrated by [¹8F]F-PSMA-1007, which helps ensure timely diagnosis and appropriate care for cancer patients.

Pharmacodynamic Activity of [18F]-Fluorthanatrace Poly(ADP-ribose) Polymerase Positron Emission Tomography in Patients With BRCA1/2-Mutated Breast Cancer Receiving Talazoparib.

PURPOSE: We tested the ability of [18F] fluorthanatrace (FTT), a radiolabeled analog of poly(ADP-ribose) polymerase (PARP)-1 inhibitors, to demonstrate target engagement on positron emission tomography (PET) scans from patients with newly diagnosed primary breast cancer receiving the PARP inhibitor (PARPi) talazoparib. METHODS: Seven patients with germline BRCA1/2 pathogenic variants underwent [18F]FTT PET-computed tomography scanning at baseline, and five underwent repeat scanning 14 days after talazoparib initiation. Maximum uptake on PET was quantified in the primary tumor, involved nodes, contralateral pectoralis muscle, and lumbar vertebra body level 3, and compared between the two time points. RESULTS: Blocking of [18F]FTT was observed on the second scan. Potentially strong but nonsignificant correlations were found between changes in tumor volume (on ultrasound at 1 month v baseline) and percentage changes in tumor-to-muscle uptake ratio at 14 days from baseline (Spearman rank correlation coefficient r = 1; P = .083); and between the highest-grade hematologic toxicity and baseline bone marrow-to-muscle (B/M) uptake ratio (r = 0.72; P = .068) and percentage change in B/M ratio at 14 days from baseline (r = 0.87; P = .058). CONCLUSION: We conclude that [18F]FTT can image target engagement by PARPi, but larger studies are needed to determine whether [18F]FTT uptake can predict response to PARPi and whether uptake of [18F]FTT in bone marrow may be an early predictor of hematologic toxicity.

A comparative study of 18F-PSMA-1007 PET/CT and pelvic MRI in newly diagnosed prostate cancer.

PURPOSE: To evaluate the difference in the diagnostic efficacy of 18F-PSMA-1007 PET/CT and pelvic MRI in primary prostate cancer, as well as the correlation between the two methods and histopathological parameters and serum PSA levels. METHODS: A total of 41 patients with suspected prostate cancer who underwent 18F-PSMA-1007 PET/CT imaging in our department from 2018 to 2023 were retrospectively collected. All patients underwent 18F-PSMA-1007 PET/CT and MRI scans. The sensitivity, PPV and diagnostic accuracy of MRI and 18F-PSMA-1007 PET/CT in the diagnosis of prostate cancer were calculated after comparing the results of MRI and 18F-PSMA-1007 PET/CT with biopsy. The Spearman test was used to calculate the correlation between 18F-PSMA-1007 PET/CT, MRI parameters, histopathological indicators, and serum PSA levels. RESULTS: Compared with histopathological results, the sensitivity, PPV and diagnostic accuracy of 18F-PSMA-1007 PET/CT in the diagnosis of prostate cancer were 95.1%, 100.0% and 95.1%, respectively. The sensitivity, PPV and diagnostic accuracy of MRI in the diagnosis of prostate cancer were 82.9%, 100.0% and 82.9%, respectively. There was a mild to moderately positive correlation between Gleason (Gs) score, Ki-67 index, serum PSA level and 18F-PSMA-1007 PET/CT parameters (p < 0.05). There was a moderately negative correlation between the expression of AMACR (P504S) and 18F-PSMA-1007 PET/CT parameters (p < 0.05). The serum PSA level and the Gs score were moderately positively correlated with the MRI parameters (p < 0.05). There was no correlation between histopathological parameters and MRI parameters (p > 0.05). CONCLUSION: Compared with MRI, 18F-PSMA-1007 PET/CT has higher sensitivity and diagnostic accuracy in the detection of malignant prostate tumors. In addition, the Ki-67 index and AMACR (P504S) expression were only correlated with 18F-PSMA-1007 PET/CT parameters. Gs score and serum PSA level were correlated with 18F-PSMA-1007 PET/CT and MRI parameters. 18F-PSMA-1007 PET/CT examination can provide certain reference values for the clinical diagnosis, evaluation, and treatment of malignant prostate tumors.

Synthesis and Preclinical Evaluation of [18F]AlF-NOTA-Asp2-PEG2-Folate as a Novel Folate-Receptor-Targeted Tracer for PET Imaging.

Recently, the folate receptor (FR) has become an exciting target for the diagnosis of FR-positive malignancies. Nevertheless, suboptimal in vivo pharmacokinetic properties, particularly high uptake in the renal and hepatobiliary systems, are important limiting factors for the clinical translation of most FR-based radiotracers. In this study, we developed a novel 18F-labeled FR-targeted positron emission tomography (PET) tracer [18F]AlF-NOTA-Asp2-PEG2-Folate modified with a hydrophilic linker (-Asp2-PEG2) to optimize its pharmacokinetic properties and conducted a comprehensive preclinical assessment. The [18F]AlF-NOTA-Asp2-PEG2-Folate was manually synthesized within 30 min with a non-decay-corrected radiochemical yield of 16.3 ± 2.0% (n = 5). Among KB cells, [18F]AlF-NOTA-Asp2-PEG2-Folate exhibited high specificity and affinity for FR. PET/CT imaging and biodistribution experiments in KB tumor-bearing mice showed decent tumor uptake (1.7 ± 0.3% ID/g) and significantly decreased uptake in kidneys and liver (22.2 ± 2.1 and 0.3 ± 0.1% ID/g at 60 min p.i., respectively) of [18F]AlF-NOTA-Asp2-PEG2-Folate, compared to the known tracer [18F]AlF-NOTA-Folate (78.6 ± 5.1 and 5.3 ± 0.5 % ID/g at 90 min p.i., respectively). The favorable properties of [18F]AlF-NOTA-Asp2-PEG2-Folate, including its efficient synthesis, decent tumor uptake, relatively low renal uptake, and rapid clearance from most normal organs, portray it as a promising PET tracer for FR-positive tumors.

Development and validation of a HPLC method for the determination of chemical and radiochemical purity of O-(2-[18F]fluoroethyl-l-tyrosine ([18F]FET)), a PET radiotracer for the imaging of brain tumor.

A novel HPLC method was developed and validated to determine radiochemical identity, radiochemical purity and chemical purity for the analysis of O-(2-[18F]fluoroethyl-l-tyrosine ([18F]FET). In this method, an analytical Phenomenex Gemini C18 column was used with an isocratic eluent of 7 % ethanol and 93 % 50 mM potassium phosphate buffer (pH = 6.9). The flow rate was 1.0 mL/min and the injection volume was 10 µL. A photo-diode array detector set at 220 nm was used for UV mass detection and a single channel, high sensitivity radiation detector was used. The method validation assays including specificity, linearity, precision, accuracy, and robustness were evaluated. Results show that the method was suitable for qualitative and quantitative determination of radiochemical and chemical purity of [18F]FET. This system has been routinely used for the analysis of more than 120 batches of [18F]FET with radiochemical yield 23.7 ± 6 % (no decay corrected) and molar activity 593 ± 284 GBq/µmole in our facility to support human use.

Comparative study of [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p as novel PD-L1 targeting PET probes for tumor imaging.

PD-L1 is expressed in many tumors but rarely in normal tissues, therefore, it can be a target of PET imaging. In this work, we developed new peptide-based PET probes [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p with yields of 20-25 % and 40-55 %, respectively. [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p were synthesized within 30 min with high molar activities. [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p showed good stability in vivo and in vitro. In vitro cell studies showed [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p target PD-L1 specifically, with high uptake of 61.52 ± 4.39 and 19.29 ± 2.17 %ID/1 million cells in B16F10 cells at 60 min, respectively. Biodistribution results showed that both [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p had lower liver accumulation. In vivo PET imaging results showed that [18F]AlF-PAI-PDL1p had a high tumor uptake of 4.23 ± 0.81 %ID/g at 2 h and increased uptake of 6.60 ± 1.01 %ID/g at 12 h. [68Ga]Ga-PAI-PDL1p also showed high tumor uptake of 2.30 ± 0.20 %ID/g at 2 h and slightly increased uptake of 3.80 ± 0.26 %ID/g at 6 h. In conclusion, [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1 seemed to be potential tracers for PET imaging of PD-L1 expression.