Application Of Positron Emission Tomography Research Articles

Clinical applications of fibroblast activation protein inhibitor positron emission tomography (FAPI-PET)

AbstractThe discovery of fibroblast activation protein inhibitor positron emission tomography (FAPI-PET) has paved the way for a new class of PET tracers that target the tumor microenvironment (TME) rather than the tumor itself. Although 18F-fluorodeoxyglucose (FDG) is the most common PET tracer used in clinical imaging of cancer, multiple studies have now shown that the family of FAP ligands commonly outperform FDG in detecting cancers, especially those known to have lower uptake on FDG-PET. Moreover, FAPI-PET will have applications in benign fibrotic or inflammatory conditions. Thus, even while new FAPI-PET tracers are in development and applications are yet to enter clinical guidelines, a significant body of literature has emerged on FAPI-PET, suggesting it will have important clinical roles. This article summarizes the current state of clinical FAPI-PET imaging as well as potential uses as a theranostic agent.

Critères d’évaluation de la TEP au 18F-FDG au cours de l’immunothérapie

Checkpoint inhibitor therapy is well established as a first-line treatment for cancer, but assessing treatment response using molecular imaging is still evolving. Evaluating response during checkpoint inhibitor therapy is challenging due to induced immune responses and immune-related adverse effects, which lead to atypical response patterns compared to traditional chemotherapy. Positron emission tomography (PET) and its various radiotracers provide functional information that is valuable for early evaluation of treatment response and can offer critical insights into the efficacy of immunotherapy. Furthermore, PET can help differentiate between patients with a complete response and those with residual disease, potentially guiding clinicians in deciding whether to continue or escalate treatment. This review offers an overview of the application of PET in predicting and evaluating treatment response to immunotherapy, highlighting its potential to refine therapeutic strategies and improve patient outcomes.

A novel method in myocardial injury risk stratification using intravenous fat emulsion as sole rapid preparation for unfasted patients to suppress myocardial 18F-fluorodeoxyglucose uptake for optimal cardiac PET imaging: a proof-of-concept randomized-crossover trial.

Optimal imaging of ischemic or inflammed myocardium via 18F-FDG PET imaging requires suppression of background carbohydrate metabolism in normal myocardium. Sole administration of intravenous lipid emulsion has not previously been used to rapidly prepare unfasted patients, such as in emergent clinical situations. In this proof-of-concept pilot, we posited that intravenous fat emulsion suppresses physiological metabolic uptake of in non-ischemic, non-inflammatory myocardium in unprepared and unfasted setting for enhanced cardiac positron emission tomography (PET) imaging. We conducted an ethics-approved, single-blind, prospective randomized crossover trial of 10 healthy volunteers from January 2020 to June 2021. Participants were unfasted and rendered hyperglycemic before being administered either high dose intravenous lipid emulsion-1.5 ml kg of 20% lipid emulsion, followed by 15 ml/kg/hr for 30mins-or saline prior to 18F-FDG injection and subsequent cardiac PET imaging. Assessors undertook image analysis for maximum standard uptake value (SUVmax), minimum standard uptake value (SUVmin) and qualitative assessment, and groups were compared using univariate analysis. The study population age was 44.5 years [IQR 32.5-56.5], with 50% male and a median BMI of 22.75 [IQR 25.0-28.5] kg/m2. The study was feasible and there were no adverse side effects from the interventions. In these participants with normal myocardium, 18F-FDG uptake was reduced by intravenous lipid emulsion as assessed by SUVmax and qualitative assessment (p = 0.042, r = 0.454 and p = 0.009, r = -0.581, respectively). Intravenous lipid emulsion suppresses background metabolic uptake of 18F-FDG even in unprepared and unfasted patients. Our findings prove and expand the possible applications for cardiac 18F-FDG PET in various settings, including in emergent settings as a means of rapid preparation in place of current more time-consuming standard protocols, allowing time-critical management to be effected.

Advanced Imaging for Localized Prostate Cancer

Background/Objectives: Prostate cancer is a prevalent malignancy often presenting without early symptoms. Advanced imaging technologies have revolutionized its diagnosis and management. This review discusses the principles, benefits, and clinical applications of multiparametric magnetic resonance imaging (mpMRI), micro-ultrasound (microUS), and prostate-specific membrane antigen positron emission tomography–computed tomography (PSMA PET/CT) in localized prostate cancer. Methods: We conducted a comprehensive literature review of recent studies and guidelines on mpMRI, microUS, and PSMA PET/CT in prostate cancer diagnosis, focusing on their applications in biopsy-naïve patients, those with previous negative biopsies, and patients under active surveillance. Results: MpMRI has demonstrated high sensitivity and negative predictive value in detecting clinically significant prostate cancer (csPCa). MicroUS, a newer technology, has shown promising results in early studies, with sensitivity and specificity comparable to mpMRI. PSMA PET/CT has emerged as a highly sensitive and specific imaging modality, particularly valuable for staging and detecting metastatic disease. All three technologies have been incorporated into urologic practice for prostate cancer diagnosis and management, with each offering unique advantages in different clinical scenarios. Conclusions: Advanced imaging techniques, including mpMRI, microUS, and PSMA PET/CT, have significantly improved the accuracy of prostate cancer diagnosis, staging, and management. These technologies enable more precise targeting of suspicious lesions during biopsy and therapy planning. However, further research, especially randomized controlled trials, is needed to fully establish the optimal use and inclusion of these imaging modalities in various stages of prostate cancer care.

Physicochemical characterization and potential cancer therapy applications of hydrogel beads loaded with doxorubicin and GaOOH nanoparticles

A new type of hybrid polymer particles capable of carrying the cytostatic drug doxorubicin and labeled with a gallium compound was prepared. These microparticles consist of a core and a hydrogel shell, which serves as the structural matrix. The shell can be employed to immobilize gallium oxide hydroxide (GaOOH) nanoparticles and the drug, resulting in hybrid beads with sizes of approximately 3.81 ± 0.09 μm. The microparticles exhibit the ability to incorporate a remarkably large amount of doxorubicin, approximately 0.96 mg per 1 mg of the polymeric carrier. Additionally, GaOOH nanoparticles can be deposited within the hydrogel layer at an amount of 0.64 mg per 1 mg of the carrier. These nanoparticles, resembling rice grains with an average size of 593 nm by 155 nm, are located on the surface of the polymer carrier. In vitro studies on breast and colon cancer cell lines revealed a pronounced cytotoxic effect of the hybrid polymer particles loaded with doxorubicin, indicating their potential for cancer therapies. Furthermore, investigations on doping the hybrid particles with the Ga-68 radioisotope demonstrated their potential application in positron emission tomography (PET) imaging. The proposed structures present a promising theranostic platform, where particles could be employed in anticancer therapies while monitoring their accumulation in the body using PET.

The impact of PET imaging on triple negative breast cancer: an updated evidence-based perspective.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptors. It predominantly affects younger women and is associated with a poor prognosis. This systematic review aims to evaluate the current role of positron emission tomography (PET) in the management of TNBC patients and to identify future research directions. We systematically searched the PubMed, Scopus, and Web of Science databases up to February 2024. A team of five researchers conducted data extraction and analysis. The quality of the selected studies was assessed using a specific evaluation form. Twenty-eight studies involving 2870 TNBC patients were included in the review. Key clinical applications of PET in TNBC included predicting pathological complete response (pCR) in patients undergoing neoadjuvant chemotherapy (NAC), assessing the prognostic value of baseline PET, and initial disease staging. Two studies utilized PSMA-ligand agents, while the majority used [18F]FDG-based PET. Significant associations were found between baseline [18F]FDG uptake and molecular biomarkers such as PDL-1, androgen receptor, and Ki67. Baseline [18F]FDG PET led to the upstaging of patients from stage IIB to stage IV, influencing treatment decisions and survival outcomes. In the NAC setting, serial PET scans measuring changes in [18F]FDG uptake, indicated by maximum standardized uptake value (SUVmax), predicted pCR with varying cut-off values correlated with different response rates. Semiquantitative parameters such as metabolic tumor volume (MTV) and PET lung index were prognostic for metastatic disease. In TNBC patients, [18F]FDG PET is essential for initial disease staging in both localized and metastatic settings. It is also useful for assessing treatment response to NAC. The ability of PET to correlate metabolic activity with molecular markers and predict treatment outcomes highlights its potential in TNBC management. Further prospective studies are needed to refine these clinical indications and establish its definitive role.

Synthesis and evaluation of bifunctional DFO2K: a modular chelator with ideal properties for zirconium-89 chelation.

The synthesis and evaluation of the newest generation of our DFO2 chelator family-DFO2K-is described. DFO2K was designed with a simple synthetic route to access different bifunctional derivatives, with each derivative having similar metal ion coordination spheres and high denticity (up to 12 coordinate) to ensure stable coordination of zirconium-89. The high denticity could potentially enhance stability with other large oxophilic radiometals. Zirconium-89 is the most popular radionuclide to pair with large macromolecules such as antibodies (immunoPET) for positron emission tomography applications. Although clinically successful, the stability of the "gold standard" chelator desferrioxamine B (DFO) can be improved as significant bone uptake is observed in animal models, despite no obvious stability issues in humans. Following the synthesis of DFO2K we assessed its radiolabeling efficiency with zirconium-89 and compared with DFO, which revealed rapid and nearly identical radiolabeling kinetics to DFO. The resultant [89Zr]Zr-DFO2K complex showed improved stability over [89Zr]Zr-DFO in different in vitro stability assays such as hydroxyapatite and 1000-fold molar excess EDTA challenges. Furthermore, biodistribution studies of the non-bifunctional chelators in healthy mice showed that [89Zr]Zr-DFO2K had a similar distribution profile and clearance to [89Zr]Zr-DFO. The bifunctional derivative p-SCN-Ph-DFO2K was conjugated to a non-specific human IgG antibody and evaluated after 2 weeks circulating in healthy female CD1 mice. Mice administered [89Zr]Zr-DFO2K-IgG showed substantially lower bone uptake in PET-CT images than [89Zr]Zr-DFO-IgG, with PET ROI data and ex vivo biodistribution revealing a statistically significantly lower bone uptake for DFO2K. Overall, owing to its high denticity, ease of synthesis, improved solubility over DFO2 and DFO2p, and stable chelation of zirconium-89, DFO2K appears to be an improved alternative chelator to DFO for zirconium-89 chelation.

11C–methionine PET/CT in meningiomas

Currently, positron emission tomography (PET) is the standard imaging modality in neuro-oncology for gliomas and metastatic lesions. The experience of PET application in meningiomas, the most frequent primary CNS neoplasms, is much less, and the interpretation of the study results has a number of differences. The aim of the study was to evaluate the possibility and peculiarities of PET application in meningiomas based on our own clinical experience and literature review. The study included 70 patients with 77 meningiomas who underwent PET/CT with 11C-methionine. The mean age at the time of examination was 57.4 years (19–86 years). The main evaluation parameter, the tumor-to-brain ratio (TBR) of 11C-methionine (11C–MET) averaged 3.13 (1.00–10.66). Meningiomas were characterized by high 11C–MET TBR, with 89.6% of cases having TBR greater than 1.5. In histologically verified WHO grade 1, 2, and 3 meningiomas, the median TBR was 4.06 [3.04, 4.57], 2.32 [2.12, 3.69], and 4.29 [2.60, 5.10] and did not differ significantly between groups. Meanwhile, in histologically unresectable slow-growing or non-growing incidental meningiomas, TBR of 11C–MET was significantly lower than in WHO grade 1 and 3 meningiomas. There was no significant difference in the accumulation index between irradiated meningiomas with tumor growth control (3.81 [2.97, 3.98]) and recurrence (3.62 [2.60, 4.30]). When irradiated and non-irradiated meningiomas of WHO grade 1, 2 and 3, as well as the combined group of grade 1–3 tumors were compared, no significant differences in 11C–MET TBR were found. The use of PET/CT in meningiomas has a number of important features. Meningiomas are characterized by high TBR of 11C–MET. According to our data PET/CT with 11C–MET does not allow differentiating between meningiomas of different degrees of malignancy – 1, 2 or 3 according to WHO. With effective radiotherapy, meningiomas show partial reduction of TBR or remain stable. Even with prolonged growth control after radiation treatment, meningiomas may still have high TBR of 11C–MET. When comparing growing and stable meningiomas, irradiated and non-irradiated tumors, no significant differences in TBR of 11C–MET are found.

Synthesizing PET images from high-field and ultra-high-field MR images using joint diffusion attention model.

Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) stand as pivotal diagnostic tools for brain disorders, offering the potential for mutually enriching disease diagnostic perspectives. However, the costs associated with PET scans and the inherent radioactivity have limited the widespread application of PET. Furthermore, it is noteworthy to highlight the promising potential of high-field and ultra-high-field neuroimaging in cognitive neuroscience research and clinical practice. With the enhancement of MRI resolution, a related question arises: can high-resolution MRI improve the quality of PETimages? This study aims to enhance the quality of synthesized PET images by leveraging the superior resolution capabilities provided by high-field and ultra-high-fieldMRI. From a statistical perspective, the joint probability distribution is considered the most direct and fundamental approach for representing the correlation between PET and MRI. In this study, we proposed a novel model, the joint diffusion attention model, namely, the joint diffusion attention model (JDAM), which primarily focuses on learning information about the joint probability distribution. JDAM consists of two primary processes: the diffusion process and the sampling process. During the diffusion process, PET gradually transforms into a Gaussian noise distribution by adding Gaussian noise, while MRI remains fixed. The central objective of the diffusion process is to learn the gradient of the logarithm of the joint probability distribution between MRI and noise PET. The sampling process operates as a predictor-corrector. The predictor initiates a reverse diffusion process, and the corrector applies Langevindynamics. Experimental results from the publicly available Alzheimer's Disease Neuroimaging Initiative dataset highlight the effectiveness of the proposed model compared to state-of-the-art (SOTA) models such as Pix2pix and CycleGAN. Significantly, synthetic PET images guided by ultra-high-field MRI exhibit marked improvements in signal-to-noise characteristics when contrasted with those generated from high-field MRI data. These results have been endorsed by medical experts, who consider the PET images synthesized through JDAM to possess scientific merit. This endorsement is based on their symmetrical features and precise representation of regions displaying hypometabolism, a hallmark of Alzheimer'sdisease. This study establishes the feasibility of generating PET images from MRI. Synthesis of PET by JDAM significantly enhances image quality compared to SOTAmodels.

Advances in the Use of Positronic Radiomolecular Imaging Agents in the Diagnosis of Parkinson's Disease

The objective of this study was to examine the potential of positron radioactive molecular imaging agents for the diagnosis of Parkinson's disease (PD). With the increasing prevalence of aging and the rising incidence of PD, early diagnosis is of paramount importance to enhance the quality of life of patients. In terms of research methods, this study analyzed the application of positron emission tomography (PET) and computed tomography (CT) technology and its combination with positron radioactive molecular imaging agents in the diagnosis of Parkinson's disease (PD), with particular emphasis on the use of glucose metabolism imaging agents, including 18F-fluoro-2-deoxy-D-glucose (18F-FDG). The findings of the study demonstrate that the integration of PET/CT technology with positron radioactive molecular imaging agents offers a comprehensive approach to the diagnosis of PD. This approach provides valuable functional and metabolic information about the brain of PD patients, and enables the accurate localization of lesions with high specificity and sensitivity, making it a highly effective and well-tolerated diagnostic tool. The utilization of positron radioactive molecular imaging agents in the diagnosis of PD has the potential to significantly enhance the accuracy and efficiency of diagnosis, thereby facilitating early detection and treatment of PD.

Experimental concept validation of a proton therapy range verification system using scattered proton measurements

In recent years, the application of positron emission tomography (PET) for the dose range verification of proton therapy has been proposed. However, the positron distribution is determined by the nuclear reaction cross section; hence, PET may not accurately reflect the dose range primarily influenced by ionization. Consequently, a proton dose range verification system based on scattered proton measurements has been suggested owing to the similarity in the reaction cross section between Rutherford scattering and ionization. While previous investigations have only verified the feasibility of dose range estimation through simple simulations, the objective of this study is to demonstrate this feasibility through experimental investigation. In this paper, we established an experimental framework for capturing scattered protons and introduced an algorithm that compares measured signal patterns with a reference database to estimate the dose range. A therapeutic beam was irradiated onto the abdominal region of a human phantom, and scattered protons were measured using scintillation detectors placed on the phantom surface. Consequently, the dose range was estimated with error margins of 4.22 ± 3.68 and 0.60 ± 1.03 mm along the beam axis and perpendicular directions to the Bragg peak, respectively. While providing the same level of Bragg peak positioning accuracy as conventional methods, our system features small size, cost-effectiveness, and system simplicity. One notable limitation of our method is the challenge in achieving precise detector positioning, which is crucial for accurate dose range estimation. Future research will focus on improving detector-position accuracy and exploring advanced algorithms for signal analysis to further refine dose range estimations.

Diagnosis of Melanoma with 61Cu-Labeled PET Tracer.

Until the recent years, substances containing radioactive 61Cu were strongly considered as potential positron-emitting radiopharmaceuticals for use in positron emission tomography (PET) applications; however, due to their suitably long half-life, and generator-independent and cost-effective production, they seem to be economically viable for human imaging. Since malignant melanoma (MM) is a major public health problem, its early diagnosis is a crucial contributor to long-term survival, which can be achieved using radiolabeled α-melanocyte-stimulating hormone analog NAPamide derivatives. Here, we report on the physicochemical features of a new CB-15aneN5-based Cu(II) complex ([Cu(KFTGdiac)]-) and the ex vivo and in vivo characterization of its NAPamide conjugate. The rigid chelate possesses prompt complex formation and suitable inertness (t1/2 = 18.4 min in 5.0 M HCl at 50 °C), as well as excellent features in the diagnosis of B16-F10 melanoma tumors (T/M(SUVs) (in vivo): 12.7, %ID/g: 6.6 ± 0.3, T/M (ex vivo): 22).

Chemical and biophysical characterization of novel potassium channel blocker 3-fluoro-5-methylpyridin-4-amine

4-aminopyridine (4AP) is a potassium (K+) channel blocker used clinically to improve walking in people with multiple sclerosis (MS). 4AP binds to exposed K+ channels in demyelinated axons, reducing the leakage of intracellular K+ and enhancing impulse conduction. Multiple derivatives of 4AP capable of blocking K+ channels have been reported including three radiolabeled with positron emitting isotopes for imaging demyelinated lesions using positron emission tomography (PET). However, there remains a demand for novel molecules with suitable physicochemical properties and binding affinity that can potentially be radiolabeled and used as PET radiotracers. In this study, we introduce 3-fluoro-5-methylpyridin-4-amine (5Me3F4AP) as a novel trisubstituted K+ channel blocker with potential application in PET. 5Me3F4AP has comparable potency to 4AP and the PET tracer 3-fluoro-4-aminopyridine (3F4AP). Compared to 3F4AP, 5Me3F4AP exhibits comparable basicity (pKa = 7.46 ± 0.01 vs. 7.37 ± 0.07, P-value = 0.08), greater lipophilicity (logD = 0.664 ± 0.005 vs. 0.414 ± 0.002, P-value < 0.0001) and higher permeability to an artificial brain membrane (Pe = 88.1 ± 18.3 vs. 31.1 ± 2.9 nm/s, P-value = 0.03). 5Me3F4AP is also more stable towards oxidation in vitro by the cytochrome P450 enzyme CYP2E1 (IC50 = 36.2 ± 2.5 vs. 15.4 ± 5.1, P-value = 0.0003); the enzyme responsible for the metabolism of 4AP and 3F4AP. Taken together, 5Me3F4AP has promising properties as a candidate for PET imaging warranting additional investigation.

Diagnostic Positron Emission Tomography Imaging with Zirconium-89 Desferrioxamine B Squaramide: From Bench to Bedside.

Molecular imaging with antibodies radiolabeled with positron-emitting radionuclides combines the affinity and selectivity of antibodies with the sensitivity of Positron Emission Tomography (PET). PET imaging allows the visualization and quantification of the biodistribution of the injected radiolabeled antibody, which can be used to characterize specific biological interactions in individual patients. This characterization can provide information about the engagement of the antibody with a molecular target such as receptors present in elevated levels in tumors as well as providing insight into the distribution and clearance of the antibody. Potential applications of clinical PET with radiolabeled antibodies include identifying patients for targeted therapies, characterization of heterogeneous disease, and monitoring treatment response.Antibodies often take several days to clear from the blood pool and localize in tumors, so PET imaging with radiolabeled antibodies requires the use of a radionuclide with a similar radioactive half-life. Zirconium-89 is a positron-emitting radionuclide that has a radioactive half-life of 78 h and relatively low positron emission energy that is well suited to radiolabeling antibodies. It is essential that the zirconium-89 radionuclide be attached to the antibody through chemistry that provides an agent that is stable in vivo with respect to the dissociation of the radionuclide without compromising the biological activity of the antibody.This Account focuses on our research using a simple derivative of the bacterial siderophore desferrioxamine (DFO) with a squaramide ester functional group, DFO-squaramide (DFOSq), to link the chelator to antibodies. In our work, we produce conjugates with an average ∼4 chelators per antibody, and this does not compromise the binding of the antibody to the target. The resulting antibody conjugates of DFOSq are stable and can be easily radiolabeled with zirconium-89 in high radiochemical yields and purity. Automated methods for the radiolabeling of DFOSq-antibody conjugates have been developed to support multicenter clinical trials. Evaluation of several DFOSq conjugates with antibodies and low molecular weight targeting agents in tumor mouse models gave PET images with high tumor uptake and low background. The promising preclinical results supported the translation of this chemistry to human clinical trials using two different radiolabeled antibodies. The potential clinical impact of these ongoing clinical trials is discussed.The use of DFOSq to radiolabel relatively low molecular weight targeting molecules, peptides, and peptide mimetics is also presented. Low molecular weight molecules typically clear the blood pool and accumulate in target tissue more rapidly than antibodies, so they are usually radiolabeled with positron-emitting radionuclides with shorter radioactive half-lives such as fluorine-18 (t1/2 ∼ 110 min) or gallium-68 (t1/2 ∼ 68 min). Radiolabeling peptides and peptide mimetics with zirconium-89, with its longer radioactive half-life (t1/2 = 78 h), could facilitate the centralized manufacture and distribution of radiolabeled tracers. In addition, the ability to image patients at later time points with zirconium-89 based agents (e.g. 4-24 h after injection) may also allow the delineation of small or low-uptake disease sites as the delayed imaging results in increased clearance of the tracer from nontarget tissue and lower background signal.

Construction and evaluation of a large radiation detector for Positron Emission Tomography applications

Large arrays of pixelated scintillator potentially have application in economical construction of PET scanners. In this investigation, we constructed and evaluated a detector with an active area of 32.26 × 13.47 cm2. It is based on a 218 × 91 array of 1.4 × 1.4 × 15 mm3 LYSO elements (pitch 1.48 mm). Scintillation light is detected with a 5 × 12 array of silicon photomultipliers (SiPM) arrays. Each array consists of an 8 × 8 array of 3 × 3 mm2 (pitch 3.35 mm) SiPMs. Performance of these devices are enhanced and stabilized by cooling them. Testing revealed that the detector was able to detect 90% of the theoretically detectable 511 keV photons. The resolvability index (a measure of the ability to identify individual detector elements from background) is 0.24 ± 0.04. Additionally, the average energy resolution for the complete detector is 18.3%. These results compare well with those reported for much smaller detector modules.

Radioisotope production using lasers: From basic science to applications

The discovery of chirped pulse amplification has led to great improvements in laser technology, enabling energetic laser beams to be compressed to pulse durations of tens of femtoseconds and focused to a few micrometers. Protons with energies of tens of MeV can be accelerated using, for instance, target normal sheath acceleration and focused on secondary targets. Under such conditions, nuclear reactions can occur, with the production of radioisotopes suitable for medical application. The use of high-repetition lasers to produce such isotopes is competitive with conventional methods mostly based on accelerators. In this paper, we study the production of 67Cu, 63Zn, 18F, and 11C, which are currently used in positron emission tomography and other applications. At the same time, we study the reactions 10B(p,α)7Be and 70Zn(p,4n)67Ga to put further constraints on the proton distributions at different angles, as well as the reaction 11B(p,α)8Be relevant for energy production. The experiment was performed at the 1 PW laser facility at Vega III in Salamanca, Spain. Angular distributions of radioisotopes in the forward (with respect to the laser direction) and backward directions were measured using a high purity germanium detector. Our results are in reasonable agreement with numerical estimates obtained following the approach of Kimura and Bonasera [Nucl. Instrum. Methods Phys. Res., Sect. A 637, 164–170 (2011)].

Performance Comparison of DOI-Encoding PET Detectors Based on 1.1-mm Pitch BGO Arrays With Different Reflectors.

Bismuth germanate (BGO)-based positron emission tomography (PET) detectors are potential candidates for low-dose imaging PET scanners, owing to the high stopping power and low background radiation of BGO. In this paper, we compared the performance of two dual-ended readout PET detectors based on 15 × 15 BGO arrays. Both arrays had the same 1.1 mm pitch but utilized different reflectors - barium sulfate (BaSO4) and enhanced specular reflector film (ESR) - for high-resolution PET applications. The detectors were constructed with Hamamatsu 13361-2050-08 SiPM arrays. Each BGO element had dimensions of 1.02 × 1.02 × 20 mm3. The lateral surfaces of the BGO elements were unpolished (saw-cut), while the two ends were polished. Flood histograms showed that the detector based on the BGO array with BaSO4 reflector had much better crystal identification and depth-of-interaction (DOI) resolution. Specifically, the energy, DOI, and timing resolutions for the detector using the BGO array with BaSO4 reflector were 19.8 ± 1.5%, 4.13 ± 0.48 mm, and 2.80 ± 0.23 ns, respectively. In contrast, the values obtained using the BGO array with ESR reflector were 20.9 ± 2.1%, 7.69 ± 1.92 mm, and 2.93 ± 0.20 ns, respectively.

Radiosynthesis, structural identification and in vitro tissue binding study of [18F]FNA-S-ACooP, a novel radiopeptide for targeted PET imaging of fatty acid binding protein 3

BackgroundFatty acid binding protein 3 (FABP3) is a target with clinical relevance and the peptide ligand ACooP has been identified for FABP3 targeting. ACooP is a linear decapeptide containing a free amino and thiol group, which provides opportunities for conjugation. This work is to develop methods for radiolabeling of ACooP with fluorine-18 (18F) for positron emission tomography (PET) applications, and evaluate the binding of the radiolabeled ACooP in human tumor tissue sections with high FABP3 expression.ResultsThe prosthetic compound 6-[18F]fluoronicotinic acid 4-nitrophenyl ester was conveniently prepared with an on-resin 18F-fluorination in 29.9% radiochemical yield and 96.6% radiochemical purity. Interestingly, 6-[18F]fluoronicotinic acid 4-nitrophenyl ester conjugated to ACooP exclusively by S-acylation instead of the expected N-acylation, and the chemical identity of the product [18F]FNA-S-ACooP was confirmed. In the in vitro binding experiments, [18F]FNA-S-ACooP exhibited heterogeneous and high focal binding in malignant tissue sections, where we also observed abundant FABP3 positivity by immunofluorescence staining. Blocking study further confirmed the [18F]FNA-S-ACooP binding specificity.ConclusionsFABP3 targeted ACooP peptide was successfully radiolabeled by S-acylation using 6-[18F]fluoronicotinic acid 4-nitrophenyl ester as the prosthetic compound. The tissue binding and blocking studies together with anti-FABP3 immunostaining confirmed [18F]FNA-S-ACooP binding specificity. Further preclinical studies of [18F]FNA-S-ACooP are warranted.

Characterisation of a high granularity multi-channel prompt γ-ray detection system prototype for proton range verification based on the PETsys TOFPET2 ASIC

Proton therapy requires range verification in order to exploit its full potential. One of the most promising approaches is to monitor prompt gamma-rays produced by nuclear interactions of the therapeutic particles in the patient tissues. A detector with a wide energy range from 100 keV to 15 MeV and excellent time resolution is required to achieve millimetric precision in proton range. During patient treatment, the detector count rates are usually above 106 s-1 and the fraction of pile-up events is very high for commonly used fast inorganic scintillators. We are investigating a full acceptance approach with increased granularity in order to reduce the size of the scintillators and consequently the count rate per channel. Stacking the scintillators in matrices requires suitable multi-channel photo-multipliers and a fitting acquisition system. Here, we present two geometries of CeBr3 crystals 5×5×20 mm3 and 10×10×30 mm3, together with modern silicon photo-multipliers (SiPM) adapted to work with the PETsys TOFPET2 ASIC. The TOFPET2 ASIC was developed for Time-of-Flight Positron Emission Tomography (TOF-PET) applications. Here we show its potential for higher gamma-ray energies and future hybrid imaging. First results of energy resolution of 6.1%–7.8% are achieved at 3.42 MeV using a 241Am9Be source. The time resolution was found to be below 100 ps and studies of the count rates and the dead time of the full system were performed. Different SiPM models are analysed for their impact on the coincidence time resolution.

Light-Driven Radiochemistry with Fluorine-18, Carbon-11 and Zirconium-89.

This review discusses recent advances in light-driven radiochemistry for three key isotopes: fluorine-18, carbon-11, and zirconium-89, and their applications in positron emission tomography (PET). In the case of fluorine-18, the predominant approach involves the use of cyclotron-produced [18F]fluoride or reagents derived thereof. Light serves to activate either the substrate or the fluorine-18 labeled reagent. Advancements in carbon-11 photo-mediated radiochemistry have been leveraged for the radiolabeling of small molecules, achieving various transformations, including 11C-methylation, 11C-carboxylation, 11C-carbonylation, and 11C-cyanation. Contrastingly, zirconium-89 photo-mediated radiochemistry differs from fluorine-18 and carbon-11 approaches. In these cases, light facilitates a postlabeling click reaction, which has proven valuable for the labeling of large biomolecules such as monoclonal antibodies (mAbs). New technological developments, such as the incorporation of photoreactors in commercial radiosynthesizers, illustrate the commitment the field is making in embracing photochemistry. Taken together, these advances in photo-mediated radiochemistry enable radiochemists to apply new retrosynthetic strategies in accessing novel PET radiotracers.