Effective Preparation of [18F]Flumazenil Using Copper-Mediated Late-Stage Radiofluorination of a Stannyl Precursor

(1) Background: [¹⁸F]Flumazenil 1 ([¹⁸F]FMZ) is an established positron emission tomography (PET) radiotracer for the imaging of the gamma-aminobutyric acid (GABA) receptor subtype, GABA_A in the brain. The production of [¹⁸F]FMZ 1 for its clinical use has proven to be challenging, requiring harsh radiochemical conditions, while affording low radiochemical yields. Fully characterized, new methods for the improved production of [¹⁸F]FMZ 1 are needed. (2) Methods: We investigate the use of late-stage copper-mediated radiofluorination of aryl stannanes to improve the production of [¹⁸F]FMZ 1 that is suitable for clinical use. Mass spectrometry was used to identify the chemical by-products that were produced under the reaction conditions. (3) Results: The radiosynthesis of [¹⁸F]FMZ 1 was fully automated using the iPhase FlexLab radiochemistry module, affording a 22.2 ± 2.7% (n = 5) decay-corrected yield after 80 min. [¹⁸F]FMZ 1 was obtained with a high radiochemical purity (>98%) and molar activity (247.9 ± 25.9 GBq/µmol). (4) Conclusions: The copper-mediated radiofluorination of the stannyl precursor is an effective strategy for the production of clinically suitable [¹⁸F]FMZ 1.     

An Improved Synthesis of N-(4-[18F]Fluorobenzoyl)-Interleukin-2 for the Preclinical PET Imaging of Tumour-Infiltrating T-cells in CT26 and MC38 Colon Cancer Models

Positron emission tomography (PET) imaging of activated T-cells with N-(4-[¹⁸F]fluorobenzoyl)-interleukin-2 ([¹⁸F]FB-IL-2) may be a promising tool for patient management to aid in the assessment of clinical responses to immune therapeutics. Unfortunately, existing radiosynthetic methods are very low yielding due to complex and time-consuming chemical processes. Herein, we report an improved method for the synthesis of [¹⁸F]FB-IL-2, which reduces synthesis time and improves radiochemical yield. With this optimized approach, [¹⁸F]FB-IL-2 was prepared with a non-decay-corrected radiochemical yield of 3.8 ± 0.7% from [¹⁸F]fluoride, 3.8 times higher than previously reported methods. In vitro experiments showed that the radiotracer was stable with good radiochemical purity (>95%), confirmed its identity and showed preferential binding to activated mouse peripheral blood mononuclear cells. Dynamic PET imaging and ex vivo biodistribution studies in naïve Balb/c mice showed organ distribution and kinetics comparable to earlier published data on [¹⁸F]FB-IL-2. Significant improvements in the radiochemical manufacture of [¹⁸F]FB-IL-2 facilitates access to this promising PET imaging radiopharmaceutical, which may, in turn, provide useful insights into different tumour phenotypes and a greater understanding of the cellular nature and differential immune microenvironments that are critical to understand and develop new treatments for cancers.     

A novel 18F-labelled high affinity agent for PET imaging of the translocator protein

The translocator protein (TSPO) is an important target for imaging focal neuroinflammation in diseases such as brain cancer, stroke and neurodegeneration, but current tracers for non-invasive imaging of TSPO have important limitations. We present the synthesis and evaluation of a novel 3-fluoromethylquinoline-2-carboxamide, AB5186, which was prepared in eight steps using a one-pot two component indium(iii)-catalysed reaction for the rapid and efficient assembly of the 4-phenylquinoline core. Biological assessment and the implementation of a physicochemical study showed AB5186 to have low nanomolar affinity for TSPO, as well as optimal plasma protein binding and membrane permeability properties. Generation of [¹⁸F]-AB5186 through ¹⁸F incorporation was achieved in good radiochemical yield and subsequent in vitro and ex vivo autoradiography revealed the ability of this compound to bind with specificity to TSPO in mouse glioblastoma xenografts. Initial positron emission tomography imaging of a glioma bearing mouse and a healthy baboon support the potential for [¹⁸F]-AB5186 use as a radiotracer for non-invasive TSPO imaging in vivo.     

Enantioselective synthesis of no-carrier added (NCA) 6-[18F]Fluoro-L-Dopa

6-[¹⁸F]Fluoro-L-Dopa (6-FDOPA) is the analogue of L-Dopa, the biosynthesis precursor for dopamine. As a PET tracer, it was widely applied for the presynaptic dopamine function studies in human brain. The application of a chiral phase-transfer-catalyst (PTC) in enantioselective synthesis of N.C.A. 6-[¹⁸F]Fluoro-L-Dopa has been developed recently. An improved procedure was described in this study. The labeling precursor (6-Trimethylammoniumveratraldehyde Triflate) and PTC (O-Allyl-N-(9)-anthracenylcinchonidinium Bromide) were synthesized. A successful synthesis route was developed for the preparation of 6-[¹⁸F]Fluoro-L-Dopa with high radiochemical yields (4-9%, decay uncorrected) and short synthesis time(80min). The radiochemical purity was over 99% and no D-isomer was detected by HPLC analysis using a chiral mobile phase.     

Fully automated and simplified radiosynthesis of [<Superscript>18</Superscript>F]-3′-deoxy-3′-fluorothymidine using anhydro precursor and single neutral alumina column purification

[¹⁸F]-3′-deoxy-3′-fluorothymidine ([¹⁸F]FLT) is an established positron emission tomograph (PET)—radiopharmaceutical to study cell-proliferation rate in tumors. Very low practical yield, uncertain and time-consuming high performance liquid chromatography (HPLC) purification, are the main obstacles for the routine use of [¹⁸F]FLT in clinical PET. To obviate these difficulties, we have developed a fully automated radiosynthesis procedure for [¹⁸F]FLT using 5′-O-(4,4′-dimethoxytriphenylmethyl)-2,3′-anhydro-thymidine (DMTThy) and simplified single neutral alumina column purification. The [¹⁸F]FLT yield was 8.48 ± 0.93% (n = 5) (without radioactive decay correction) in a synthesis time of 68 ± 3 min. The radiochemical purity was greater than 95% as confirmed by analytical HPLC using reference standard FLT and also free of non-radioactive impurity. Soluble aluminum in the final product was much below the permissible limits. Di-methyl sulfoxide (DMSO), the reaction medium, could be detected in the final product in trace amounts, well below the permissible levels. The synthesized [¹⁸F]FLT was sterile and bacterial endotoxin free by appropriate tests. PET imaging study in normal rabbits showed distinct localization of [¹⁸F]FLT in organs having rapid cell division rate like bone marrow, guts and snout and the excretion was through the renal route. There were no significant uptakes in bone and brain. The former finding confirms the in vivo stability of the [¹⁸F]FLT. This simplified radiosynthesis procedure can easily be adapted in any commercial or indigenous [¹⁸F]FDG synthesis module for routine [¹⁸F]FLT synthesis without the need of additional automation for HPLC purification.     

Synthesis of <Emphasis Type="Italic">O</Emphasis>-(2-[<Superscript>18</Superscript>F]fluoroethyl)-<Emphasis Type="Italic">L</Emphasis>-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET), a fluorine-18 labeled analogue of tyrosine, has been synthesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is completed within 50 min. The radiochemical yield is about 40% (no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [¹⁸F]FET shows rapid, high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle (T/M) and tumor-to-blood (T/B) of [¹⁸F]FET are similar to those of [¹⁸F]FDG, but the ratios of tumor-to-brain (T/Br) are 2–3 times higher than that of [¹⁸F]FDG. Autoradiography of [¹⁸F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET. Supported by the Knowledge Innovation Project of Chinese Academy of Sciences (No. KJCX1-SW-08) and the National Natural Science Foundation of China (Grant No. 30371634)     

Automated synthesis of hypoxia imaging agent [18F]FMISO based upon a modified Explora FDG4 module

A new automated synthesis procedure of 1-H-1-(3-[¹⁸F]fluoro-2-hydroxypropyl)-2-nitroimidazole ([¹⁸F]FMISO), a specific hypoxia imaging agent with great significances for the noninvasive, dynamic hypoxia evaluation of cancer, was developed by modifying Explora FDG₄ module, a commercial [¹⁸F]FDG production system, in this study. Its radiochemical synthesis was carried out via two sequent reaction steps, i.e. the nucleophilic displacement of labeling precursor 1-(2′-nitro-1′-imidazolyl)-2-O-tetrahydropyranyl-3-O-tosyl-propanediol (NITTP) with activated ¹⁸F- ion at 100 °C for 8 minutes, and the following hydrolysis with 1M HCl at 100 °C for 5 minutes and neutralization with 1M NaOH. Two-pot reaction with two independent separations was adopted to assure the good separation of final product via solid phase extraction (SPE) based upon combined Sep-pak cartridges instead of high performance liquid chromatography (HPLC). This fast, reliable preparation route of ¹⁸F-FMISO could complete within 50 minutes with about 55% of high radiochemical yield (with decay correction) and more than 98% of good radiochemical purity. The modified module could perform multiple runs of production of [¹⁸F]FMISO.     

Automated synthesis of symmetric integrin αvβ3-targeted radiotracer [18F]FP-PEG3-β-Glu-RGD2

A automated synthesis of symmetric integrin α_vβ₃-targeted radiotracer [¹⁸F]FP-PEG₃-β-Glu-RGD₂ was carried out by multi-step procedure on the modified PET-MF-2V-IT-I synthesizer. Firstly, the prosthetic group of 4-nitrophenyl 2-[¹⁸F]fluoropropionate ([¹⁸F]NFP) was automated synthesized by a convenient three-step, one-pot procedure. Secondly, [¹⁸F]FP-PEG₃-β-Glu-RGD₂ was synthesized by coupling [¹⁸F]NFP with the symmetric RGD-peptide (PEG₃-β-Glu-RGD₂) and purified by a solid-phase extraction cartridge. The radiochemical yields of [¹⁸F]NFP were 35 ± 5 % (n = 10, decay-corrected) based on [¹⁸F]fluoride in 80 min. [¹⁸F]FP-PEG₃-β-Glu-RGD₂ was obtained with yield 40 ± 10 % (n = 5, decay-corrected) from [¹⁸F]NFP within 20 min. The radiochemical purity of [¹⁸F]FP-PEG₃-β-Glu-RGD₂ was greater than 98 %.     

Radiochemical Synthesis of 4-[18F]FluorobenzylAzide and Its Conjugation with EGFR-Specific Aptamers

Central nervous system tumors related to gliomas are of neuroectodermal origin and cover about 30% of all primary brain tumors. Glioma is not susceptible to any therapy and surgical attack remains one of the main approaches to its treatment. Preoperative tumor imaging methods, such as positron emission tomography (PET), are currently used to distinguish malignant tissue to increase the accuracy of glioma removal. However, PET is lacking a specific visualization of cells possessing certain molecular markers. Here, we report an application of aptamers to enhancing specificity in imaging tumor cells bearing the epidermal growth factor receptor (EGFR). Glioblastoma is characterized by increased EGFR expression, as well as mutations of this receptor associated with active division, migration, and adhesion of tumor cells. Since 2021, EGFR has been included into the WHO classification of gliomas as a molecular genetic marker. To obtain conjugates of aptamers GR20 and GOL1-specific to EGFR, a 4-[¹⁸F]fluorobenzylazide radiotracer was used as a synthon. For the production of the synthon, a method of automatic synthesis on an Eckert & Ziegler research module was adapted and modified using spirocyclic iodonium ylide as a precursor. Conjugation of 4-[¹⁸F]fluorobenzylazide and alkyne-modified aptamers was carried out using Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) with/without the TBTA ligand. As a result, it was possible to obtain ¹⁸F-labelled conjugates with 97% radiochemical purity for [¹⁸F]FB-GR20 and 98% for [¹⁸F]FB-GOL1. The obtained conjugates can be used for further studies in PET analysis on model animals with grafted glioblastoma.     

Module-assisted one-pot synthesis of [18F]SFB for radiolabeling proteins

The need of reliable production of N-succinimidyl 4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB), a versatile ¹⁸F-labeled prosthetic group for protein labeling, has increased dramatically due to the easy availability of proteins or their engineered derivatives for targeted molecular imaging. A module-assisted radiosynthesis of [¹⁸F]SFB was developed using a three-step, one-pot procedure and ethyl 4-(trimethylammonium)benzoate triflate (1) as the starting material. The radiochemical transformations were carried out in a general-purpose, custom-made module and streamlined by an anhydrous deprotection strategy using t-BuOK/DMSO. After HPLC-purification, [¹⁸F]SFB was synthesized in radiochemical yields of 20–30% (n > 10, not decay-corrected) and excellent radiochemical and chemical purities (>98%). The total synthesis and purification time required is ~90 min. Using the purified [¹⁸F]SFB, three ¹⁸F-labeled proteins, bovine serum albumin (BSA), chicken egg albumin (CEA) and transferrin, were synthesized in yields of 61.0–79.5%. The ¹⁸F-Annexin V for apoptosis imaging was also produced in 5% radiolabeling yield and >95% radiochemical purity.     

Radiosynthesis of 10-(2-[18F]fluoroethoxy)-20(S)-camptothecin as a potential positron emission tomography tracer for the imaging of topoisomerase I in cancers

The preparation of 10-(2-[¹⁸F]fluoroethoxy)-20(S)-camptothecin, a potential positron emission tomography tracer for the imaging of topoisomerase I in cancers, is described. 10-(2-[¹⁸F]Fluoroethoxy)-20(S)-camptothecin was synthesized by the [¹⁸F]fluoroalkylation of the corresponding hydroxy precursor molecule with 2-[¹⁸F]fluoroethyl bromide ([¹⁸F]FEtBr) in dimethylsulfoxide (DMSO) at 55 °C for 20 min; this was followed by purification using high performance liquid chromatography (HPLC) with a total preparation time of 60 min. The overall radiochemical yield was approximately 5.4–12 % (uncorrected), and the radiochemical purity was above 96 %.     

(S)-2-((S)-2-(4-(3-[18F]fluoropropyl)benzamido)-3-phenylpropanamido)pentanedioic acid labeled with 18F

As degradation product of Antineoplaston A10 in vivo, phenylacetyl glutamine showed antitumor activities. According to literatures, we designed and radiosynthesized a phenylacetyl glutamine derivative, which was achieved under a mild reaction condition. Evaluations in vitro and in vivo were performed on tumor bearing mice. Excitingly, the radiochemical purity of (S)-2-((S)-2-(4-(3-fluoropropyl)benzamido)-3-phenylpropanamido)pentanedioic acid ([¹⁸F]FBPPA) was 98%, and besides the best radiochemical yield was up to 46%. T/Bl (Tumor/Blood) and T/M (Tumor/Muscle) ratios of [¹⁸F]FBPPA at 60 min post injection were 2.33 and 3.51. Meanwhile, it showed satisfied stability in vitro and in vivo, compared with 2-[¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG). Although [¹⁸F]FBPPA deserved further studies to make optimizations on its structure, the results revealed it might become a potential PET imaging agent for detecting tumors.     

Synthesis of [18F]F-γ-T-3, a Redox-Silent γ-Tocotrienol (γ-T-3) Vitamin E Analogue for Image-Based In Vivo Studies of Vitamin E Biodistribution and Dynamics

Vitamin E, a natural antioxidant, is of interest to scientists, health care pundits and faddists; its nutritional and biomedical attributes may be validated, anecdotal or fantasy. Vitamin E is a mixture of tocopherols (TPs) and tocotrienols (T-3s), each class having four substitutional isomers (α-, β-, γ-, δ-). Vitamin E analogues attain only low concentrations in most tissues, necessitating exacting invasive techniques for analytical research. Quantitative positron emission tomography (PET) with an F-18-labeled molecular probe would expedite access to Vitamin E’s biodistributions and pharmacokinetics via non-invasive temporal imaging. (R)-6-(3-[¹⁸F]Fluoropropoxy)-2,7,8-trimethyl-2-(4,8,12-trimethyltrideca-3,7,11-trien-1-yl)-chromane ([¹⁸F]F-γ-T-3) was prepared for this purpose. [¹⁸F]F-γ-T-3 was synthesized from γ-T-3 in two steps: (i) 1,3-di-O-tosylpropane was introduced at C6-O to form TsO-γ-T-3, and (ii) reaction of this tosylate with [¹⁸F]fluoride in DMF/K₂₂₂. Non-radioactive F-γ-T-3 was synthesized by reaction of γ-T-3 with 3-fluoropropyl methanesulfonate. [¹⁸F]F-γ-T-3 biodistribution in a murine tumor model was imaged using a small-animal PET scanner. F-γ-T-3 was prepared in 61% chemical yield. [¹⁸F]F-γ-T-3 was synthesized in acceptable radiochemical yield (RCY 12%) with high radiochemical purity (>99% RCP) in 45 min. Preliminary F-18 PET images in mice showed upper abdominal accumulation with evidence of renal clearance, only low concentrations in the thorax (lung/heart) and head, and rapid clearance from blood. [¹⁸F]F-γ-T-3 shows promise as an F-18 PET tracer for detailed in vivo studies of Vitamin E. The labeling procedure provides acceptable RCY, high RCP and pertinence to all eight Vitamin E analogues.     

In vivo biodistribution of pancreatic-derived factor using 18F-labeled PANDER PET imaging

The purpose of this study was to investigate in vivo biodistribution and potential target tissues of pancreatic-derived factor (PANDER, FAM3B) using ¹⁸F-labeled PANDER positron emission tomography (PET) imaging. ¹⁸F-Labeled PANDER ([¹⁸F]FB-PANDER) was prepared by reaction of PANDER and N-succinimidyl-4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB). The uncorrected radiochemical yield of [¹⁸F]FB-PANDER was 15.2 ± 3.4 % (n = 4) based on [¹⁸F]SFB within the total synthesis time of 30 min. In vivo biodistribution of [¹⁸F]FB-PANDER in nomal mice and PET imaging demonstrated high uptake of the radiotracer in urinary bladder, kidneys and gall bladder, and fast clearance from kidneys and gall bladder. Also, moderate uptake in blood, liver, pancreas, small intestine and bone, low uptake in brain and muscle, and almost no uptake in S180 fibrosarcoma tissue were observed. The results indicated that the major excretion route of PANDER was through renal-urinary bladder and biliary system, and no obvious binding targets of PANDER in the main organs and S180 fibrosarcoma tissue were found.     

Synthesis and evaluation of N-(2-[18F]fluoro-4-nitrobenzoyl)glucosamine: a preliminary report

d-glucosamine at concentration of certain range could kill tumor cells without influencing normal cells. There are also some reports on the antitumor activity of d-glucosamine and its derivatives in murine models. It was therefore postulated that d-glucosamine might have the potential to invade tumor cells. We designed and radiosynthesized a glucosamine derivative, N-(2-[¹⁸F]fluoro-4-nitrobenzoyl)glucosamine ([¹⁸F]FNBG([¹⁸F]7)). Evaluations in vitro and in vivo were performed on tumor bearing mice. Excitingly, the radiochemical purity of [¹⁸F]FNBG([¹⁸F]7) was 99%, and besides the best radiochemical yield was up to 35%. The best T/Bl (Tumor/Blood) and T/M (Tumor/Muscle) ratios of [¹⁸F]FNBG([¹⁸F]7) were 4.40 and 4.84. Although [¹⁸F]FNBG([¹⁸F]7) deserved further studies, the results revealed it might become a potential PET imaging agent for detecting tumors.     

Preparation and Evaluation of [18F]AlF-NOTA-NOC for PET Imaging of Neuroendocrine Tumors: Comparison to [68Ga]Ga-DOTA/NOTA-NOC

Background: The somatostatin receptors 1–5 are overexpressed on neuroendocrine neoplasms and, as such, represent a favorable target for molecular imaging. This study investigates the potential of [¹⁸F]AlF-NOTA-[1-Nal³]-Octreotide and compares it in vivo to DOTA- and NOTA-[1-Nal³]-Octreotide radiolabeled with gallium-68. Methods: DOTA- and NOTA-NOC were radiolabeled with gallium-68 and NOTA-NOC with [¹⁸F]AlF. Biodistributions of the three radioligands were evaluated in AR42J xenografted mice at 1 h p.i and for [¹⁸F]AlF at 3 h p.i. Preclinical PET/CT was applied to confirm the general uptake pattern. Results: Gallium-68 was incorporated into DOTA- and NOTA-NOC in yields and radiochemical purities greater than 96.5%. NOTA-NOC was radiolabeled with [¹⁸F]AlF in yields of 38 ± 8% and radiochemical purity above 99% after purification. The biodistribution in tumor-bearing mice showed a high uptake in tumors of 26.4 ± 10.8 %ID/g for [⁶⁸Ga]Ga-DOTA-NOC and 25.7 ± 5.8 %ID/g for [⁶⁸Ga]Ga-NOTA-NOC. Additionally, [¹⁸F]AlF-NOTA-NOC exhibited a tumor uptake of 37.3 ± 10.5 %ID/g for [¹⁸F]AlF-NOTA-NOC, which further increased to 42.1 ± 5.3 %ID/g at 3 h p.i. Conclusions: The high tumor uptake of all radioligands was observed. However, [¹⁸F]AlF-NOTA-NOC surpassed the other clinically well-established radiotracers in vivo, especially at 3 h p.i. The tumor-to-blood and -liver ratios increased significantly over three hours for [¹⁸F]AlF-NOTA-NOC, making it possible to detect liver metastases. Therefore, [¹⁸F]AlF demonstrates promise as a surrogate pseudo-radiometal to gallium-68.     

A one-step fully automated radio-synthesis of a dopamine transporter PET imaging agent 18F-FECNT and its in vivo evaluations

2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[¹⁸F]fluoroethyl)nortropane ([¹⁸F]-FECNT) is a potential dopamine transporter PET imaging agent. However, its current radio-synthesis is tedious and time consuming. In this article, we reported a fully automatic method for the synthesis of [¹⁸F] FECNT through only one step, using a TRACERlab FX_N module, with decay corrected radiochemical yield of 25 ± 5 % (n = 5). The total synthesis time was 50–55 min. The synthesized [¹⁸F]FECNT was evaluated in vivo in Parkinson’s disease model rats.     

An improved,regioselective synthesis of the radiolabelling precursor for the translocator protein targeting positron emission tomography imaging radiotracer [F]GE-180

[¹⁸F]GE-180 has been demonstrated to be a promising new positron emission tomography radiotracer for targeting translocator protein. PET imaging of TSPO will enable measurement of neuroinflammation and microglia activity in vivo. The synthetic route used in the initial discovery of GE-180, whilst enabling the rapid evaluation of the structure–activity relationships (SAR) in this molecular class, was not high yielding and not suitable for scale-up. Here we present an optimised route towards GE-180 and the radiolabelling precursor of [¹⁸F]GE-180 with significantly improved yields due to a strategy which improves the regioselectivity of the key indole formation step of the synthesis.     

Copper‐Mediated Aromatic Radiofluorination Revisited: Efficient Production of PET Tracers on a Preparative Scale

Two novel methods for copper‐mediated aromatic nucleophilic radiofluorination were recently reported. Evaluation of these methods reveals that, although both are efficient in small‐scale experiments, they are inoperative for the production of positron emission tomography (PET) tracers. Since high base content turned out to be responsible for low radiochemical conversions, a “low base” protocol has been developed which affords ¹⁸F‐labeled arenes from diaryliodonium salts and aryl pinacol boronates in reasonable yields. Furthermore, implementation of our “minimalist” approach to the copper‐mediated [¹⁸F]‐fluorination of (mesityl)(aryl)iodonium salts allows the preparation of ¹⁸F‐labeled arenes in excellent RCCs. The novel radiofluorination method circumvents time‐consuming azeotropic drying and avoids the utilization of base and other additives, such as cryptands. Furthermore, this procedure enables the production of clinically relevant PET tracers; [¹⁸F]FDA, 4‐[¹⁸F]FPhe, and [¹⁸F]DAA1106 are obtained in good isolated radiochemical yields. Additionally, [¹⁸F]DAA1106 has been evaluated in a rat stroke model and demonstrates excellent potential for visualization of translocator protein 18 kDa overexpression associated with neuroinflammation after ischemic stroke.     

Analysis of Pros and Cons in Using [68Ga]Ga-PSMA-11 and [18F]PSMA-1007: Production,Costs, and PET/CT Applications in Patients with Prostate Cancer

The aim of this work is to compare [⁶⁸Ga]Ga-PSMA-11 and [¹⁸F]PSMA-1007 PET/CT as imaging agents in patients with prostate cancer (PCa). Comparisons were made by evaluating times and costs of the radiolabeling process, imaging features including pharmacokinetics, and impact on patient management. The analysis of advantages and drawbacks of both radioligands might help to make a better choice based on firm data. For [⁶⁸Ga]Ga-PSMA-11, the radiochemical yield (RCY) using a low starting activity (L, average activity of 596.55 ± 37.97 MBq) was of 80.98 ± 0.05%, while using a high one (H, average activity of 1436.27 ± 68.68 MBq), the RCY was 71.48 ± 0.04%. Thus, increased starting activities of [⁶⁸Ga]-chloride negatively influenced the RCY. A similar scenario occurred for [¹⁸F]PSMA-1007. The rate of detection of PCa lesions by Positron Emission Tomography/Computed Tomography (PET/CT) was similar for both radioligands, while their distribution in normal organs significantly differed. Furthermore, similar patterns of biodistribution were found among [¹⁸F]PSMA-1007, [⁶⁸Ga]Ga-PSMA-11, and [¹⁷⁷Lu]Lu-PSMA-617, the most used agent for RLT. Moreover, the analysis of economical aspects for each single batch of production corrected for the number of allowed PET/CT examinations suggested major advantages of [¹⁸F]PSMA-1007 compared with [⁶⁸Ga]Ga-PSMA-11. Data from this study should support the proper choice in the selection of the PSMA PET radioligand to use on the basis of the cases to study.