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Background: As constituents of the reticuloendothelial system, the spleen and bone marrow (BM) have been recognized as integral components of the systemic inflammatory response in cancer contexts, thereby serving as predictive indicators for assessing cancer prognosis. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has attained widespread utilization for staging, assessing treatment response, and prognostication in lymphoma patients. Several investigations have proposed that focal increased 18F-FDG uptake in the BM or spleen may correlate with malignant involvement in lymphoma. However, scant data exist regarding the implications of diffuse BM and splenic uptake. This study aimed to explore the relationships between metabolic parameters of the spleen and BM on 18F-FDG PET/CT and inflammatory markers, and to assess their prognostic value in patients with lymphoma. Methods: A retrospective analysis was conducted on 118 patients newly diagnosed with malignant lymphoma, who underwent 18F-FDG PET/CT and exhibited diffuse increased splenic or BM uptake in 18F-FDG PET/CT imaging. The mean standardized uptake value (SUV) of the spleen, BM, and liver was calculated. The association between metabolic variables and systemic inflammatory markers was investigated, and the prognostic significance of clinicopathological and PET parameters was assessed using overall survival (OS) and progression-free survival (PFS). Results: A statistically significant correlation was found between the spleen-to-liver SUV ratio (SLR) and inflammatory markers such as C-reactive protein (r=0.264, P=0.007) and platelet-to-lymphocyte ratio (r=0.227, P=0.021). No significant correlation was observed between BM-to-liver SUV ratio (BLR) and hematologic parameters, while concordance analysis revealed a fair agreement between BLR and bone marrow biopsy (BMB) (Cohen's Kappa-κ =0.271, P=0.002). In patients with aggressive non-Hodgkin lymphoma, both SLR [P=0.017, HR 2.715, 95% confidence interval (CI): 0.875-8.428] and BLR (P=0.044, HR 0.795, 95% CI: 0.348-1.813) were significantly linked to OS, while SLR (P=0.019, HR 2.223, 95% CI: 1.139-4.342) emerged as a significant prognostic factor for PFS. Conclusions: This study highlighted that diffuse increased splenic 18F-FDG uptake in lymphoma patients was closely associated with inflammation, whereas diffuse BM uptake was likely attributable to BM infiltration rather than inflammatory changes. Furthermore, both parameters held promise as prognostic indicators for patients with aggressive lymphoma.

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Background: Nonsteroidal immunosuppressive therapy is a potential therapeutic strategy for cardiac sarcoidosis. However, it is not recommended as an established treatment option. This study aimed to demonstrate the clinical outcomes of patients with cardiac sarcoidosis using nonsteroidal immunosuppressants through the ILLUstration of the Management and PrognosIs of JapaNese PATiEnts with Cardiac Sarcoidosis multicenter retrospective registry. Methods: From a cohort of 512 patients, 426 who received corticosteroid therapy and 26 who received other immunosuppressive therapy were included for analysis. Clinical outcomes included all-cause death, fatal ventricular arrhythmic events (FVAE), and worsening heart failure with hospitalization. Results: Nonsteroidal immunosuppressants were used for retained fluorodeoxyglucose uptake in the heart (n = 14), corticosteroid side effects (n = 7), ventricular arrhythmia (n = 4), complete atrioventricular block (n = 2), worsened extracardiac sarcoidosis (n = 2), and other reasons (n = 2). They comprised of methotrexate (n = 20), cyclosporine (n = 2), cyclophosphamide (n = 2), and azathioprine (n = 3). After the addition of a nonsteroidal immunosuppressant, corticosteroids were reduced in 14 of 26 patients (5 [5-17] mg), although no patient discontinued corticosteroids. Of the 14 patients, decreased fluorodeoxyglucose uptake was observed in seven at follow-up. Clinical outcomes were observed in 11 patients (42.3 %). Detected events included all-cause death in five patients (19.2 %), FVAE in four (15.4 %), and worsening heart failure with hospitalization in five (19.2 %), with some overlap. Conclusions: Nonsteroidal immunosuppressive therapy may be a possible treatment option for patients who are not stabilized with corticosteroids alone or develop corticosteroid side effects.

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About 75% of breast tumors show an overexpression of the estradiol receptor (ER), making it a valuable target for tumor diagnosis and therapy. To date, 16α-[18F]fluoroestradiol (FES) is the only FDA-approved imaging probe for the positron emission tomography (PET) imaging of ER-positive (ER+) breast cancer. However, FES has the drawback of a high retention in the liver. Therefore, the aim of this study was the development and preclinical evaluation of estradiol (E2) derivatives with different lipophilicity. Three 18F-labeled prosthetic groups (two glycosyl and one PEG azide) were chosen for conjugation with ethinyl estradiol (EE) by 18F-CuAAC (Cu-catalyzed azide-alkyne cycloaddition). The cellular uptake in ER+ MCF-7 tumor cells was highest for the less hydrophilic derivative (18F-TA-Glyco-EE). In nude mice bearing different breast tumors (ER+ MCF-7 and T47D versus ER- MDA-MB-231), 18F-TA-Glyco-EE revealed a high uptake in the liver (13%ID/g, 30 min p.i.), which decreased over 90 min to 1.2%ID/g, indicating fast hepatobiliary clearance. The statistically significant difference of 18F-TA-Glyco-EE uptake in T47D compared to MDA-MB-231 tumors at 60-90 min p.i. indicated ER-specific uptake, whereas in vivo PET imaging did not provide evidence for specific uptake of 18F-TA-Glyco-EE in MCF-7 tumors, probably due to ER occupation by E2 after E2-dependent MCF-7 tumor growth in mice. However, in vitro autoradiography revealed a high specific binding of 18F-TA-Glyco-EE to ER+ tumor slices. We conclude that 18F-TA-Glyco-EE, with its increased hydrophilicity after deacetylation in the blood and thus rapid washout from non-target tissues, may be a viable alternative to FES for the PET imaging of breast cancer.

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BACKGROUND: Radiofluorination of single domain antibodies (sdAbs) via N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) has shown to be a promising strategy in the development of sdAb-based PET tracers. While automation of the prosthetic group (PG) [18F]SFB production, has been successfully reported, no practical method for large scale sdAb labelling has been reported. Therefore, we optimized and automated the PG production, enabling a subsequently efficient manual conjugation reaction to an anti-fibroblast activation protein (FAP)-α sdAb (4AH29) and an anti-folate receptor (FR)-α sdAb (2BD42). Both the alpha isoform of FAP and the FR are established tumour markers. FAP-α is known to be overexpressed mainly by cancer-associated fibroblasts in breast, ovarian, and other cancers, while its expression in normal tissues is low or undetectable. FR-α has an elevated expression in epithelial cancers, such as ovarian, brain and lung cancers. Non-invasive imaging techniques, such as PET-imaging, using tracers targeting specific tumour markers can provide molecular information over both the tumour and its environment, which aides in the diagnosis, therapy selection and assessment of the cancer treatment. RESULTS: [18F]SFB was synthesized using a fully automated three-step, one-pot reaction. The total procedure time was 54 min and results in [18F]SFB with a RCP > 90% and a RCY d.c. of 44 ± 4% (n = 13). The manual conjugation reaction after purification produced [18F]FB-sdAbs with a RCP > 95%, an end of synthesis activity > 600 MBq and an apparent molar activity > 10 GBq/µmol. Overall RCY d.c., corrected to the trapping of [18F]F- on the QMA, were 9% (n = 1) and 5 ± 2% (n = 3) for [18F]FB-2BD42 and [18F]FB-4AH29, respectively. CONCLUSION: [18F]SFB synthesis was successfully automated and upscaled on a Trasis AllInOne module. The anti-hFAP-α and anti-hFR-α sdAbs were radiofluorinated, yielding similar RCYs d.c. and RCPs, showing the potential of this method as a generic radiofluorination strategy for sdAbs. The radiofluorinated sdAbs showed a favourable biodistribution pattern and are attractive for further characterization as new PET tracers for FAP-α and FR-α imaging.

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Perfusion dynamics play a vital role in delivering essential nutrients and oxygen to tissues while removing metabolic waste products. Imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) use contrast agents to visualize perfusion and clearance patterns; however, each technique has specific limitations. Hybrid PET/MRI combines the quantitative power and sensitivity of PET with the high functional and anatomical detail of MRI and holds great promise for precision in molecular imaging. However, the development of dual PET/MRI probes has been hampered by challenging synthesis and radiolabeling. Here, we present a novel PET/MRI probe, [18F][Gd(FL1)], which exhibits excellent stability comparable to macrocyclic MRI contrast agents used in clinical practice. The unique molecular design of [18F][Gd(FL1)] allows selective and expeditious radiolabeling of the gadolinium chelate in the final synthetic step. Leveraging the strengths of MRI and PET signals, the probe enables quantitative in vivo mapping of perfusion and excretion dynamics through an innovative voxel-based analysis. The diagnostic capabilities of [18F][Gd(FL1)] were demonstrated in a pilot study on healthy mice, successfully detecting early cases of unilateral renal dysfunction. This study introduces a new approach for PET/MRI and emphasizes a streamlined probe design for improved diagnostic accuracy.

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Due to the continuous rise in global incidence and severity of invasive fungal infections (IFIs), particularly among immunocompromised and immunodeficient patients, there is an urgent demand for swift and accurate fungal pathogen diagnosis. Therefore, the need for fungal-specific positron emission tomography (PET) imaging agents that can detect the infection in the early stages is increasing. Cellobiose, a disaccharide, is readily metabolized by fungal pathogens such as Aspergillus species. Recently, our group reported fluorine-18 labeled cellobiose, 2-deoxy-2-[18F]fluorocellobiose ([18F]FCB), for specific imaging of Aspergillus infection. The positive imaging findings with very low background signal on delayed imaging make this ligand a promising fungal-specific imaging ligand. Inspired by this result, the decision was made to automate the radiolabeling procedure for better reproducibility and to facilitate clinical translation. A Trasis AllInOne (Trasis AIO) automated module was used for this purpose. The reagent vials contain commercially available 2-deoxy-2-[18F]fluoroglucose ([18F]FDG), glucose-1-phosphate, and enzyme (cellobiose phosphorylase). A Sep-Pak cartridge was used to purify the tracer. The overall radiochemical yield was 50%-70% (n = 6, decay corrected) in 75-min synthesis time with a radiochemical purity of > 98%. This is a highly reliable protocol to produce current good manufacturing practice (cGMP)-compliant [18F]FCB for clinical PET imaging.

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Follicular thyroid cancer is the second-most common type of thyroid cancer after papillary thyroid cancer. Metastases to the mandible and maxillofacial region are rare. Our study presents a 55-year-old patient who underwent total thyroidectomy for follicular thyroid cancer and subsequent radioactive iodine therapy. Sixteen years after diagnosis, elevated thyroglobulin levels suggested disease recurrence. Using advanced imaging techniques - Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography scan, bone scintigraphy, and posttreatment I-131 scan-an unexpected metastatic site was identified: the left mandibular condyle. A biopsy confirmed the presence of metastatic follicular thyroid cancer.

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BACKGROUND: Positron emission tomography (PET) is now an established diagnostic method for myocardial perfusion imaging (MPI) in coronary artery disease, which is the main cause of death globally. The available tracers show several limitations, therefore, the 18F-labelled tracer is in high demand nowadays. The preclinical studies on normal Wistar rats aimed to characterise two potential, novel radiotracers, [18F]SYN1 and [18F]SYN2, to evaluate which is a better candidate for PET MPI cardiotracer. RESULTS: The dynamic microPET images showed rapid myocardial uptake for both tracers. However, the uptake was higher and also stable for [18F]SYN2, with an average standardized uptake value of 3.8. The biodistribution studies confirmed that [18F]SYN2 uptake in the cardiac muscle was high and stable (3.02%ID/g at 15 min and 2.79%ID/g at 6 h) compared to [18F]SYN1 (1.84%ID/g at 15 min and 0.32%ID/g at 6 h). The critical organs determined in dosimetry studies were the small intestine and the kidneys. The estimated effective dose for humans was 0.00714 mSv/MBq for [18F]SYN1 and 0.0109 mSv/MBq for [18F]SYN2. The tested dose level of 2 mg/kg was considered to be the No Observed Adverse Effect Level (NOAEL) for both candidates. The better results were achieved for [18F]SYN2, therefore, further preclinical studies were conducted only for this tracer. Radioligand binding assays showed significant responses in 3 from 68 assays: muscarinic acetylcholine M1 and M2 receptors and potassium channel hERG. The compound was mostly metabolised via an oxidative N-dealkylation, while the fluor substituent was not separated from the molecule. CONCLUSION: [18F]SYN2 showed a favourable pharmacodynamic and pharmacokinetic profile, which enabled a clear visualization of the heart in microPET. The compound was well-tolerated in studies in normal rats with moderate radiation exposure. The results encourage further exploration of [18F]SYN2 in clinical studies.

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PURPOSE: The angiotensin converting enzyme 2 (ACE2) plays a regulatory role in the cardiovascular system and serves SARS-CoV-2 as an entry receptor. The aim of this study was to synthesize and evaluate radiofluorinated derivatives of the ACE2 inhibitor MLN-4760. [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 were demonstrated to be suitable for non-invasive imaging of ACE2, potentially enabling a better understanding of its expression dynamics. METHODS: Computational molecular modeling, based on the structures of human ACE2 (hACE2) and mouse ACE2 (mACE2), revealed that the ACE2-binding modes of F-MLN-4760 and F-Aza-MLN-4760 were similar to that of MLN-4760. Co-crystallization of the hACE2/F-MLN-4760 protein complex was performed for confirmation. Displacement experiments using [3H]MLN-4760 enabled the determination of the binding affinities of the synthesized F-MLN-4760 and F-Aza-MLN-4760 to hACE2 expressed in HEK-ACE2 cells. Aryl trimethylstannane-based and pyridine-based radiofluorination precursors were synthesized and used for the preparation of the respective radiotracers. [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 were evaluated with regard to the uptake in HEK-ACE2 and HEK-ACE cells and in vitro binding to tissue sections of HEK-ACE2 xenografts and normal organs of mice. Biodistribution and PET/CT imaging studies of [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 were performed using HEK-ACE2 and HEK-ACE xenografted nude mice. RESULTS: Crystallography data revealed an equal hACE2-binding mode for F-MLN-4760 as previously found for MLN-4760. Moreover, computer-based modeling indicated that similar binding to hACE2 and mACE2 holds true for both, F-MLN-4760 and F-Aza-MLN-4760, as is the case for MLN-4760. The IC50 values were three-fold and seven-fold higher for F-MLN-4760 and F-Aza-MLN-4760, respectively, than for MLN-4760. [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 were obtained in 1.4 ± 0.3 GBq and 0.5 ± 0.1 GBq activity with > 99% radiochemical purity in a 5.3% and 1.2% radiochemical yield, respectively. Uptake in HEK-ACE2 cells was higher for [18F]F-MLN-4760 (67 ± 9%) than for [18F]F-Aza-MLN-4760 (37 ± 8%) after 3-h incubation while negligible uptake was seen in HEK-ACE cells (< 0.3%). [18F]F-MLN-4760 and [18F]F-Aza-MLN-4760 accumulated specifically in HEK-ACE2 xenografts of mice (13 ± 2% IA/g and 15 ± 2% IA/g at 1 h p.i.) with almost no uptake observed in HEK-ACE xenografts (< 0.3% IA/g). This was confirmed by PET/CT imaging, which also visualized unspecific accumulation in the gall bladder and intestinal tract. CONCLUSION: Both radiotracers showed specific and selective binding to ACE2 in vitro and in vivo. [18F]F-MLN-4760 was, however, obtained in higher yields and the ACE2-binding affinity was superior over that of [18F]F-Aza-MLN-4760. [18F]F-MLN-4760 would, thus, be the candidate of choice for further development in view of its use for PET imaging of ACE2.

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Radiolabeled peptides are valuable tools for diagnosis or therapies; they are often radiofluorinated using an indirect approach based on an F-18 prosthetic group. Herein, we are reporting our results on the F-18 radiolabeling of three peptides using two different methods based on click reactions. The first one used the well-known CuAAC reaction, and the second one is based on our recently reported hetero-Diels-Alder (HDA) using a dithioesters (thia-Diels-Alder) reaction. Both methods have been automated, and the 18F-peptides were obtained in similar yields and synthesis time (37-39% decay corrected yields by both methods in 120-140 min). However, to obtain similar yields, the CuAAC needs a large amount of copper along with many additives, while the HDA is a catalyst and metal-free reaction necessitating only an appropriate ratio of water/ethanol. The HDA can therefore be considered as a minimalist method offering easy access to fluorine-18 labeled peptides and making it a valuable additional tool for the indirect and site-specific labeling of peptides or biomolecules.

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Acute exacerbation of idiopathic interstitial pneumonias (AE-IIPs) is a disease associated with a poor prognosis in patients with IIPs. However, the specific characteristics of fluorine-18 2-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging for AE-IIPs remain unclear. Herein, we present the case of a patient with lung cancer combined with IIPs who underwent 18F-FDG PET/CT at the early onset of AE-IIPs. The scan, conducted 18 days post-bronchoscopy for lung cancer evaluation, revealed AE-IIPs before the onset of respiratory failure. New ground-glass opacities appeared, accompanied by significant 18F-FDG accumulation extending beyond these regions. To the best of our knowledge, this report represents the first assessment of 18F-FDG PET/CT images at the early onset of AE-IIPs before respiratory failure in humans. The observed features in this PET image could potentially contribute to our understanding of the pathophysiology of AE-IIPs.

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Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder. Plexiform neurofibromas (PNFs) are benign tumors commonly formed in patients with NF1. PNFs have a high incidence of developing into malignant peripheral nerve sheath tumors (MPNSTs) with a 5-year survival rate of only 30%. Therefore, the accurate diagnosis and differentiation of MPNSTs from benign PNFs are critical to patient management. We studied a fluorine-18 labeled tryptophan positron emission tomography (PET) radiotracer, 1-(2-[18F]fluoroethyl)-L-tryptophan (L-[18F]FETrp), to detect NF1-associated tumors in an animal model. An ex vivo biodistribution study of L-[18F]FETrp showed a similar tracer distribution and kinetics between the wild-type and triple mutant mice with the highest uptake in the pancreas. Bone uptake was stable. Brain uptake was low during the 90-min uptake period. Static PET imaging at 60 min post-injection showed L-[18F]FETrp had a comparable tumor uptake with [18F]fluorodeoxyglucose (FDG). However, L-[18F]FETrp showed a significantly higher tumor-to-brain ratio than FDG (n = 4, p < 0.05). Sixty-minute-long dynamic PET scans using the two radiotracers showed similar kidney, liver, and lung kinetics. A dysregulated tryptophan metabolism in NF1 mice was further confirmed using immunohistostaining. L-[18F]FETrp is warranted to further investigate differentiating malignant NF1 tumors from benign PNFs. The study may reveal the tryptophan-kynurenine pathway as a therapeutic target for treating NF1.

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BACKGROUND: Histone deacetylase 6 (HDAC6) is an emerging target for the treatment and diagnosis of proteinopathies. [18F]FSW-100 was recently developed as a promising brain-penetrating radioligand for HDAC6 PET imaging and the process validation of [18F]FSW-100 radiosynthesis for clinical use is complete, but no detailed synthetic strategy nor process optimisation has been reported. Here, we describe the optimisation of several processes in [18F]FSW-100 radiosynthesis, including the 18F-fluorination reaction, semipurification of the 18F-intermediate, and purification of the product by high-performance liquid chromatography (HPLC), to achieve a radiochemical yield (RCY) adequate for clinical applications of the radioligand. Our findings will aid optimisation of radiosynthesis processes in general. RESULTS: In the 18F-fluorination reaction, the amount of copper reagent was reduced without reducing the nonisolated RCY of the intermediate (50%), thus reducing the risk of copper contamination in the product injection solution. Optimising the solid-phase extraction (SPE) conditions for semipurification of the intermediate improved its recovery efficiency. The addition of anti-radiolysis reagents to the mobile phase for the HPLC purification of [18F]FSW-100 increased its activity yield in radiosynthesis using a high [18F]fluoride radioactivity of approximately 50 GBq. The SPE-based formulation method and additives for the injection solution were optimised, and the resulting [18F]FSW-100 injection solution was stable for over 2 h with a radiochemical purity of greater than 95%. CONCLUSIONS: Of all the reconsidered processes, we found that optimisation of the SPE-based semipurification of the intermediate and of the mobile phase for HPLC purification in particular improved the RCY of [18F]FSW-100, doubling it compared to that of the original protocol. The radioactivity of [18F]FSW-100 synthesized using the optimized protocol was sufficient for multiple doses for a clinical study.

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BACKGROUND: In the last decade the development of new PSMA-ligand based radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research. The most promising derivative in terms of interaction with the antigen and clinical properties has been found to be "PSMA-617", and its lutetium-177 radiolabelled version has recently been approved by EU and USA regulatory agencies for therapeutic purposes. For the above reasons, the development of new derivatives of PSMA-617 radiolabelled with fluorine-18 may still be of great interest. This paper proposes the comparison of two different PSMA-617 derivatives functionalized with NODA and RESCA chelators, respectively, radiolabelled via [18F]AlF2+ complexation. RESULTS: The organic synthesis of two PSMA-617 derivatives and their radiolabelling via [18F]AlF2+ complexation resulted to proceed efficiently and successfully. Moreover, stability in solution and in plasma has been evaluated. The whole radiosynthesis procedure has been fully automated, and the final products have been obtained with radiochemical yield and purity potentially suitable for clinical studies. The biodistribution of the two derivatives was performed both in prostate cancer and glioma tumour models. Compared with the reference [18F]F-PSMA-1007 and [18F]F-PSMA-617-RESCA, [18F]F-PSMA-617-NODA derivative showed a higher uptake in both tumors, faster clearance in non-target organs, and lower uptake in salivary glands. CONCLUSION: PSMA-617 NODA and RESCA derivatives were radiolabelled successfully via [18F]AlF2+ chelation, the former being more stable in solution and human plasma. Moreover, preclinical biodistribution studies showed that [18F]F-PSMA-617-NODA might be of potential interest for clinical applications.

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PURPOSE: There is currently no ideal radiotracer for imaging bacterial infections. Radiolabelled D-amino acids are promising candidates because they are actively incorporated into the peptidoglycan of the bacterial cell wall, a structural feature which is absent in human cells. This work describes fluorine-18 labelled analogues of D-tyrosine and D-methionine, O-(2-[18F]fluoroethyl)-D-tyrosine (D-[18F]FET) and S-(3-[18F]fluoropropyl)-D-homocysteine (D-[18F]FPHCys), and their pilot evaluation studies as potential radiotracers for imaging bacterial infection. PROCEDURES: D-[18F]FET and D-[18F]FPHCys were prepared in classical fluorination-deprotection reactions, and their uptake in Staphylococcus aureus and Pseudomonas aeruginosa was evaluated over 2 h. Heat killed bacteria were used as controls. A clinically-relevant foreign body model of S. aureus infection was established in Balb/c mice, as well as a sterile foreign body to mimic inflammation. The ex vivo biodistribution of D-[18F]FPHCys in the infected and inflamed mice was evaluated after 1 h, by dissection and gamma counting. The uptake was compared to that of [18F]FDG. RESULTS: In vitro uptake of both D-[18F]FET and D-[18F]FPHCys was specific to live bacteria. Uptake was higher in S. aureus than in P. aeruginosa for both radiotracers, and of the two, higher for D-[18F]FPHCys than D-[18F]FET. Blocking experiments with non-radioactive D-[19F]FPHCys confirmed specificity of uptake. In vivo, D-[18F]FPHCys had greater accumulation in S. aureus infection compared with sterile inflammation, which was statistically significant. As anticipated, [18F]FDG showed no significant difference in uptake between infection and inflammation. CONCLUSIONS: D-[18F]FPHCys uptake was higher in infected tissues than inflammation, and represents a fluorine-18 labelled D-AA with potential to detect a S. aureus reference strain (Xen29) in vivo. Additional studies are needed to evaluate uptake of this radiotracer in clinical isolates.

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Background: Lymphoma is a common malignant proliferative disease in which bone marrow infiltration will upstage the disease and thus affect prognosis of the disease. As of now bone marrow biopsy is considered as a reference standard to find out bone marrow involvement in lymphoma. Performing an invasive and painful intervention in all newly diagnosed lymphoma patients is controversial. PET-CT is a non-invasive technique that gives functional information about the cells using the glucose metabolism. It can detect early bone marrow and extra medullary organ involvement which can lead to restaging of the disease. These advantages make PET-CT a valuable adjunct in diagnosis of lymphoma. Aims and Objectives: Our study aims to evaluate the usefulness of 18 F-FDG PET-CT, a non-invasive, semi quantitative whole body imaging technique for detection of early bone marrow and extra medullary organ involvement in lymphoma patients which in turn can obviate the need for bone marrow study (BMS). The primary objective of study is to categorise FDG uptake in bone marrow as diffuse /unifocal /multifocal / no uptake and to correlate pattern of FDG uptake to bone marrow study. Our study also assesses the role of FDG PET/CT in staging of lymphoma. Materials and Methods: Thirty patients with newly diagnosed lymphoma in the age group 18 to 75 years of both sexes within 3 months of diagnosis and who have not been started on any treatment was included in the study. Marrow uptake on FDG PET/CT has been categorized as diffuse, unifocal, multifocal and no uptake. Agreement between bone marrow study and FDG PET/CT has been assessed by reliability analysis using Cohen's kappa. Sensitivity, specificity, PPV, NPV of PET/CT in detecting marrow involvement have been calculated. Results: The sensitivity, specificity, PPV, NPV and accuracy of 18 F-FDG PET-CT in detecting marrow involvement of lymphoma cases are 86.6%, 77.7%, 68.4%, 91.3% and 80.9% respectively. 18 F-FDG PET-CT detected bone marrow involvement in 86.6% (13 out of 15 total positive cases) cases of lymphoma which included both HL and NHL. Reliability analysis using Cohen's kappa is used to test the agreement between bone marrow study and 18F-FDG PET/CT. k value of 0.6 was obtained which showed a moderate agreement between bone marrow study and 18F-FDG PET/CT in marrow assessment. Conclusion: 18F-FDG PET/CT is a highly sensitive imaging modality which can pick up extra-nodal organ and BMI in patients with lymphoma and can upstage the disease and alter treatment strategies. PET-CT cannot completely replace the bone marrow study. However, being an invasive painful procedure, BMB can be avoided in cases with unifocal or multifocal marrow involvement on PET-CT.

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Giardia lamblia is an intestinal protozoan with oral-fecal transmission. Infection is predominantly located in the small intestine. Giardiasis causes intraepithelial lymphocytosis in the small intestine which causes false-positive fluorodeoxyglucose (FDG) uptake mimicking malignancy. We present here an interesting image of fluorine-18 FDG positron emission tomography/computed tomography showing jejunal uptake caused by giardiasis in a known case of lymphoma.

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O-([18F]Fluoroethyl)-l-tyrosine ([18F]FET) is actively transported into the brain and cancer cells by LAT1 and possibly other amino acid transporters, which enables brain tumor imaging by positron emission tomography (PET). However, tumor delivery of this probe in the presence of competing amino acids may be limited by a relatively low affinity for LAT1. The aim of the present work was to evaluate the meta-substituted [18F]FET analog m-[18F]FET and the methyl ester [18F]FET-OMe, which were designed to improve tumor delivery by altering the physicochemical, pharmacokinetic, and/or transport properties. Both tracers could be prepared with good radiochemical yields of 41-56% within 66-90 min. Preclinical evaluation with [18F]FET as a reference tracer demonstrated reduced in vitro uptake of [18F]FET-OMe by U87 glioblastoma cells and no advantage for in vivo tumor imaging. In contrast, m-[18F]FET showed significantly improved in vitro uptake and accelerated in vivo tumor accumulation in an orthotopic glioblastoma model. As such, our work identifies m-[18F]FET as a promising alternative to [18F]FET for brain tumor imaging that deserves further evaluation with regard to its transport properties and in vivo biodistribution.

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BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. The combination of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) and computed tomography (CT) has a major impact on the diagnosis, staging, treatment planning and follow-up of lung cancer patients. The maximum standardized uptake value (SUVmax) is an easily performed and most widely used semi-quantitative index for the analysis of FDG PET images and estimation of metabolic activity. This study aimed to investigate the role of PET/CT in differentiating adenocarcinoma (ADC), the most common lung cancer, from squamous cell carcinoma (SCC) by comparing FDG uptake measured as SUVmax. RESULTS: Between 2019 and 2022, 76 patients diagnosed with non-small cell lung cancer (NSCLC) at the Department of Pathology, Atatürk University Faculty of Medicine, with histopathologic evidence of adenocarcinoma or squamous cell carcinoma, underwent retrospective analysis using PET/CT scanning to measure PET parameters of the lesions and compare them with histopathology. Among 76 NSCLC patients included in the study, 43 (57%) were histopathologically diagnosed as ADC and 33 (43%) as SCC. SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values of lesions in patients with SCC were statistically significantly higher than those in patients with ADC (p values 0.007, 0.009, 0.003 and 0.04, respectively). CONCLUSIONS: Lung SCC has higher metabolic uptake values than ADC, and PET/CT can be used to differentiate them.

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BACKGROUND: Parkinson's disease is a neurodegenerative disorder that is characterized by a degeneration of the dopaminergic system. Dopamine transporter (DAT) positron emission tomography (PET) imaging has emerged as a powerful and non-invasive method to quantify dopaminergic function in the living brain. The PET radioligand, [18F]FE-PE2I, a cocaine chemical derivative, has shown promising properties for in vivo PET imaging of DAT, including high affinity and selectivity for DAT, excellent brain permeability, and favorable metabolism. The aim of the current study was to scale up the production of [18F]FE-PE2I to fulfil the increasing clinical demand for this tracer. RESULTS: Thus, a fully automated and GMP-compliant production procedure has been developed using a commercially available radiosynthesis module GE TRACERLab FX2 N. [18F]FE-PE2I was produced with a radiochemical yield of 39 ± 8% (n = 4, relative [18F]F- delivered to the module). The synthesis time was 70 min, and the molar activity was 925.3 ± 763 GBq/µmol (250 ± 20 Ci/µmol). The produced [18F]FE-PE2I was stable over 6 h at room temperature. CONCLUSION: The protocol reliably provides a sterile and pyrogen-free GMP-compliant product.