Application Of Positron Emission Tomography Research Articles

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.

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.

ConspectusMolecular 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)].

Diagnosis of Alzheimer's disease: Towards accuracy and accessibility

Alzheimer’s disease (AD) is a serious dementia afflicting aging population and is characterized by cognitive decline, amyloid-β plaques, and neurofibrillary tangles. AD substantially impairs the life quality of the victims and poses a heavy burden on the society at large. The number of people with dementia due to AD, prodromal AD, and preclinical AD is estimated to stand at roughly 3.2, 69, and 315 million worldwide, respectively. Current clinical diagnosis is based on clinical symptoms, and clinical research demonstrated that positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers had excellent diagnostic performance. However, the application of CSF biomarker tests and PET are restricted by the invasiveness and high cost. The presence of clinical symptoms means that AD pathology has been progressing for many years, and only a few drugs have been approved for the traetemnt of AD. Therefore, early diagnosis is extremely important for controlling the outcomes caused by AD. In this review, we provided an overview of developing clinical diagnostic criteria, diagnostic strategies under clinical research, developing blood based-biomarker assays, and promising nanotechnologically-based assays.

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.

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

AbstractThis 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.

A finely segmented semi-monolithic detector tailored for high-resolution PET.

Preclinical research and organ-dedicated applications use and require high (spatial-)resolution positron emission tomography (PET) detectors to visualize small structures (early) and understand biological processes at a finer level of detail. Researchers seeking to improve detector and image spatial resolution have explored various detector designs. Current commercial high-resolution systems often employ finely pixelated or monolithic scintillators, each with its limitations. We present a semi-monolithic detector, tailored for high-resolution PET applications with a spatial resolution in the range of 1mm or better, merging concepts of monolithic and pixelated crystals. The detector features LYSO slabs measuring (24×10×1)mm3, coupled to a 12×12 readout channel photosensor with 4mm pitch. The slabs are grouped in two arrays of 44 slabs each to achieve a higher optical photon density despite the fine segmentation. We employ a fan beam collimator for fast calibration to train machine-learning-based positioning models for all three dimensions, including slab identification and depth-of-interaction (DOI), utilizing gradient tree boosting (GTB). The data for all dimensions was acquired in less than 2h. Energy calculation was based on a position-dependent energy calibration. Using an analytical timing calibration, time skews were corrected for coincidence timing resolution (CTR) estimation. Leveraging machine-learning-based calibration in all three dimensions, we achieved high detector spatial resolution: down to 1.18mm full width at half maximum (FWHM) detector spatial resolution and 0.75mm mean absolute error (MAE) in the planar-monolithic direction, and 2.14mm FWHM and 1.03mm MAE for DOI at an energy window of (435-585)keV. Correct slab interaction identification in planar-segmented direction exceeded 80%, alongside an energy resolution of 12.7% and a CTR of 450ps FWHM. The introduced finely segmented, high-resolution slab detector demonstrates appealing performance characteristics suitable for high-resolution PET applications. The current benchtop-based detector calibration routine allows these detectors to be used in PET systems.

Straightforward Synthesis of DFO* - An Octadentate Chelator for Zirconium-89.

DFO* is an octadentate chelator able to form highly stable chelates with Zirconium-89 (89 Zr) for nuclear medicinal applications in Positron Emission Tomography (PET).[1,2] The synthesis of DFO* and its scale-up remains challenging by reported synthetic protocols. For this reason, we set out to develop a de novo synthesis of a hydroxamate-containing building block suitable for the coupling to the commercially available DFO (desferrioxamine B, mesylate salt) yielding, after deprotection, the desired chelator DFO* in a more efficient procedure. Highlights of the new synthesis of DFO* reported herein are less synthetic steps and the isolation of the desired product DFO* by using solid phase extraction (SPE), thus avoiding tedious HPLC purification. DFO* is obtained in excellent purity (92-98 %) and an overall yield of approximately 29 %. In addition, the isolated trifluoroacetic acid (TFA)-salt of DFO* displays an improved solubility in organic solvents (DMSO, DMF, methanol), which will facilitate its use for the preparation of structurally diverse derivatives suitable for bioconjugation chemistry and the development of 89 Zr-labeled radiotracers.

Application of positron emission tomography in molecular imaging

The authors have conducted an exploratory study in the field of application of positron emission tomography in molecular imaging. The main areas of application of the method and its advantages and limitations are identified and described according to the literature data. Conclusions have been drawn regarding the informative value of the radiation diagnostic method that in one study allows assessing the stage of the disease and obtaining an image of the primary tumor and regional and distant metastases, including previously unforeseen ones, which often radically changes the patient’s management tactics.

Functional Imaging of the Knee-A Comprehensive Review.

Knee pain is a common presenting problem in the general population. Radiographs and magnetic resonance imaging (MRI) are the cornerstones of imaging in current clinical practice. With advancements in technology, there has been increasing utilization of other modalities to evaluate knee disorders. Dynamic assessment utilizing computed tomography and portable ultrasounds have demonstrated the capacity to accurately assess and reproducibly quantify kinematics of knee disorders. Cartilage physiology can be evaluated with MRI. Emerging research has even demonstrated novel musculoskeletal applications of positron emission tomography to evaluate anterior cruciate ligament graft metabolic activity following reconstruction. As technology continues to evolve and traditional ways are improved upon, future comparative studies will elucidate the distinct advantages of the various modalities. Although radiology is still primarily an anatomic specialty, there is immense potential for functional imaging to be the standard of care. This review focuses on the most common musculoskeletal applications of functional imaging as well as future utilization.

Clinical application of MAO-B PET using 18F-THK5351 in neurological disorders.

Monoamine oxidase B (MAO-B) is an enzyme localized to the outer mitochondrial membrane and highly concentrated in astrocytes. Temporal changes in regional MAO-B levels can be used as an index of astrocytic proliferation, known as activated astrocytes or astrogliosis. MAO-B is a marker to evaluate the degree of astrogliosis. Therefore, MAO-B positron emission tomography (PET) is a powerful imaging technique for visualizing and quantifying ongoing astrogliosis through the estimate of regional MAO-B levels. Each neurodegenerative disorder generally has a characteristic distribution pattern of astrogliosis secondary to neuronal loss and pathological protein aggregation. Therefore, by imaging astrogliosis, MAO-B PET can be used as a neurodegeneration marker for identifying degenerative lesions. Any inflammation in the brain usually accompanies astrogliosis starting from an acute phase to a chronic phase. Therefore, by imaging astrogliosis, MAO-B PET can be used as a neuroinflammation marker for identifying inflammatory lesions. MAO-B levels are high in gliomas originating from astrocytes but low in lymphoid tumors. Therefore, MAO-B PET can be used as a brain tumor marker for identifying astrocytic gliomas by imaging MAO-B levels and distinguishing between astrocytic and lymphoid tumors. This review summarizes the clinical application of MAO-B PET using 18F-THK5351 as markers for neurodegeneration, neuroinflammation, and brain tumors in neurological disorders. Because we assume that MAO-B PET is clinically applied to an individual patient, we focus on visual inspection of MAO-B images at the individual patient level. Geriatr Gerontol Int 2024; 24: 31-43.

Design, synthesis and preclinical evaluation of muscarine receptor antagonists via a scaffold-hopping approach

Our research group recently identified a rearrangement product of pirenzepine as starting point for a comprehensive rational drug design approach towards orthosteric muscarinic acetylcholine receptor ligands. Chemical reduction and bioscaffold hop lead to the development of sixteen promising compounds featuring either a benzimidazole or carbamate moiety, all exhibiting comparable pharmacophoric characteristics. The synthesized compounds were characterized by NMR, HR-MS, and RP-HPLC techniques. Subsequent evaluation encompassed binding affinity assessment on CHO-hM1-5 cells, mode of action determination, and analysis of physico-chemical parameters. The CNS MPO score indicated favorable drug-like attributes and potential CNS activity for the antagonistic ligands. The most promising compounds displayed Ki-values within a desirable low nanomolar range, and their structural features allow for potential carbon-11 radiolabeling. Our optimization efforts resulted in compounds with a remarkable 138-fold increase in binding affinity compared to the previously mentioned rearrangement product towards human M5, suggesting their prospective utility in positron emission tomography applications.

Applications of PET and SPECT in Patients with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) consists of neurological development disorders that manifest before three years of age and affect social interactions, markedly restricting range of interests and activities, often associated with some degree of intellectual disability. Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are non-invasive imaging tools to investigate the function of the brain in vivo. SPECT and PET studies exploring rCBF and brain glucose metabolism in patients with ASD have been performed, providing important insights into the brain regions involved in ASD. Abnormalities in serotonergic, dopaminergic, GABAergic, cholinergic, and glutamatergic systems have been suggested to contribute to the observed distorted brain circuitry associated with ASD. However, the specificity of such abnormalities needs to be fully clarified because schizophrenia and other psychiatric diseases have been shown to present with comparable changes in neurotransmitter systems. Neuroinflammation could also play a role in the development of autism. Therefore, ASD is a complicated process involving a number of factors. It is mandatory to perform more research studies to determine the molecular cornerstone of ASD and to improve our comprehension of the clinical correlates of ASD.

Study experimental time resolution limits of recent ASICs at Weeroc with different SiPMs and scintillators

Medical applications, such as Positron Emission Tomography (PET), and space applications, such as Light Detection and Ranging (LIDAR), are in need of highly specialized ASICs. Weeroc, in collaboration with different partners, is highly involved in developing a new generation of front-end ASICs. In the context of a joined LIDAR project among Weeroc, CNES, and Airbus, Weeroc is working on the development of Liroc, an ASIC for space LIDAR application. Weeroc is also working on advancing ASICs for medical applications with Radioroc under development and intended to be used for PET applications. This study experimentally evaluates the time resolution limits of these ASICs in different configurations, with some of the most recent silicon photomultiplier (SiPM) technologies available on the market, coupled to different scintillation crystals. The best single-photon time resolution (SPTR) was achieved using FBK NUV-HD SiPMs with an FWHM of 90 ps with Liroc and 73 ps with Radioroc. Furthermore, the coincidence time resolution (CTR) of Radioroc was studied with different crystal sizes. Using a large LYSO:Ce,Ca crystal of (3 × 3 × 20 mm3) with Broadcom Near UltraViolet-Metal in Trench (NUV-MT) yields a CTR of 127 ps (FWHM). The best CTR of Radioroc was determined to 83 ps (FWHM) with Broadcom NUV-MT SiPMs coupled to LYSO:Ce,Ca (2 × 2 × 3 mm3)) from Taiwan Applied Crystal (TAC).

Advancements and Future Outlook of PET/CT-Guided Interventions

Advancements in minimally invasive technology, coupled with imaging breakthroughs, have empowered the field of interventional radiology to achieve unparalleled precision in image-guided diagnosis and treatment while simultaneously reducing periprocedural morbidity. Molecular imaging, which provides valuable physiological and metabolic information alongside anatomical localization, can expand the capabilities of image-guided interventions. Among various molecular imaging techniques, positron emission tomography (PET) stands out for its superior spatial resolution and ability to acquire quantitative data. PET has emerged as a crucial tool for oncologic imaging and plays a pivotal role in both staging and the assessment of treatment responses. Typically used in combination with computed tomography (CT) (PET/CT) and occasionally with magnetic resonance imaging MRI (PET/MRI), PET as a hybrid imaging approach offers enhanced insights into disease progression and response. In recent years, PET has also found its way into image-guided interventions, especially within the rapidly expanding field of interventional oncology. This review aims to explore the current and evolving role of metabolic imaging, specifically PET, in interventional oncology. By delving into the unique advantages and applications of PET in guiding oncological interventions and assessing response, we seek to highlight the increasing significance of this modality in the realm of interventional radiology.

Automated Synthesis and Preclinical Evaluation of Optimized Integrin α6-Targeted Positron Emission Tomography Imaging of Pancreatic Cancer.

Integrin α6 has been considered a promising biomarker, is overexpressed in many tumors, and plays a vital role in tumor formation, recurrence, and metastasis. In this study, we identified a novel high-affinity integrin α6-targeted peptide named RD2 (Arg-Trp-Tyr-Asp-PEG4)2-Lys-Lys and developed a 18F-radiolabeled peptide tracer ([18F]-AlF-NOTA-RD2) and evaluated its potential application in positron emission tomography (PET) imaging of pancreatic cancer. [18F]-AlF-NOTA-RD2 was produced using GMP (Good Manufacturing Practice of Medical Products)-compliant automatic radiosynthesis on a single GE FASTLab2 cassette-type synthesis module. The stability of [18F]-AlF-NOTA-RD2 was analyzed in phosphate-buffered saline (PBS) and fetal bovine serum (FBS). The cell uptake assay of the tracer was assessed using PANC-1 cells. In addition, small-animal PET imaging and biodistribution studies of [18F]-AlF-NOTA-RD2 were performed in pancreatic cancer subcutaneous tumor-bearing mice. The PET tracer [18F]-AlF-NOTA-RD2 was obtained with a radiochemical yield of 23.7 ± 4.7%, radiochemical purity of >99%, and molar activity of 165.7 ± 59.1 GBq/μmol. [18F]-AlF-NOTA-RD2 exhibited good in vitro stability in PBS and FBS. LogP octanol water value for the tracer was -2.28 ± 0.05 (n = 3). The binding affinity of RD2 to the integrin α6 protein (Kd = 0.13 ± 3.65 μM, n = 3) was significantly higher than that of the RWY (CRWYDENAC) (Kd = 6.97 ± 1.44 μM, n = 3). Small-animal PET imaging and biodistribution also revealed that [18F]-AlF-NOTA-RD2 displayed rapid and good tumor uptake and lower liver background uptake in PANC-1 tumor-bearing mice. [18F]-AlF-NOTA-RD2 showed significant radioactivity accumulation in tumors and was successfully blocked by NOTA-RD2. Compared with [18F]-FDG, [18F]-AlF-NOTA-RD2 PET imaging and biodistribution studies in PANC-1 xenograft tumor-bearing mice confirmed a good tumor-to-muscle ratio (8.69 ± 2.03 vs 1.41 ± 0.23, respectively) at 0.5 h and (2.99 ± 3.02 vs 1.43 ± 0.17, respectively) at 1 h post injection. Autoradiography of human pancreatic cancer tumor tissues further confirmed high accumulation of [18F]-AlF-NOTA-RD2. In summary, we developed an optimized integrin α6-targeted imaging tracer and obtained high radioactivity products with a cassette-type synthesis module; moreover, the tracer exhibited good binding affinity with integrin α6 and good target specificity for PANC-1 cells in xenograft pancreatic tumor-bearing mice, demonstrating its promising application as a noninvasive PET radiotracer of integrin α6 expression in pancreatic cancer.