PET Tracer For Imaging Research Articles

18F]TRACK, a PET tracer for imaging of tropomyosin receptor kinases (Trk): Efficient radiosynthesis and preliminary evaluation in the TgF344‐AD rat model of Alzheimer’s disease

AbstractBackgroundA family of tropomyosin receptor kinases (TrkA/B/C) plays important roles in the regulation of neuronal differentiation, growth, and survival via their interactions with neurotrophins. A growing body of literature suggests the downregulation of Trk in many neurodegenerative conditions of the central nervous system (CNS), including Alzheimer’s disease (AD). We recently reported the development of [18F]TRACK, the PET tracers for in vivo imaging of TrkB and its first in‐human study. Here, we wish to report a fully automated GMP‐compliant radiosynthesis of [18F]TRACK at high radiochemical purity (RCP) and molar activity and its preliminary evaluation in wild‐type and a transgenic rat model of AD.MethodRadiosynthesis was performed using Scintomics GRP automated module via copper‐catalyzed 18F‐fluorination of the chiral boron pinacolate precursor. Brain imaging in wild‐type (n = 3) and TgF344‐AD rat models (n = 2) at 23 months was performed on microPET Concord R4 scanner.Result[18F]TRACK was synthesized with a 5.0±1.4% radiochemical yield not corrected for decay (activity range 95‐154 mCi) with >99% RCP and molar activities of 250 ± 75 GBq/µmol (n = 6). The synthesis was fully automated and all batches passed quality control procedures, including chemical purity, sterility and pyrogenicity. The tracer showed moderate brain uptake in wild‐type rats with the highest accumulation in the thalamus (SUVmax = 1.56 ± 0.28, 10 min post‐injection), consistent with the brain regional distribution in humans acquired in a parallel study. Preliminary data suggests lower tracer uptake in TgF344‐AD rat model of AD in thalamus, striatum and frontal cortex compared to wild‐type animals.ConclusionThis study demonstrated the feasibility of the GMP‐compliant production of [18F]TRACK in sufficient doses and molar activities for scanning multiple subjects per day or long range deliveries. Preliminary biodistribution studies showed moderate brain uptake of the tracer with preferential accumulation in the thalamus across species. These findings warrants further studies of Trk brain expression and its implication in neurodegenerative and psychiatric pathologies using [18F]TRACK.

Prospective evaluation of the utility of concurrent 18F-FDG PET/CT and 68Ga-DOTA-TOC imaging in gastroenteropancreatic neuroendocrine neoplasms (GEPNENs): The PETNET study.

4022 Background: Somatostatin receptor imaging (SRI) is a standard of care for patients with GEPNETs. The additional value of concurrent 18F-FDG PET/CT (FDG PET) remains unclear. We reviewed a prospective functional imaging study to determine the utility of FDG PET in GEPNENs. Methods: PETNET is a prospective study in British Columbia, Canada, which provides all 68Ga-DOTA-TOC (DOTA PET) imaging in the province. Every patient receives a DOTA PET scan and an FDG PET within 30 days. PETNET enrolls all patients with an indication for SRI. Scans are ordered per treating physician discretion at any point in the disease course. This abstract focuses on the WD-GEPNEN population. Only the first dual functional imaging scans were analyzed and FDG was interpreted qualitatively (positive/negative). Results: From 04/2017-01/2023, 375 patients with NEN were enrolled, 165 (44%) with metastatic GEPNENs. Baseline characteristics are described. Median time between scans was 4 days (IQR 1-11). The proportion of patients with positive FDG PET at baseline increased with WHO grade. For patients with well differentiated G1 to G3 GEPNENs (N=161), overall survival was significantly lower with a positive FDG PET (HR: 4.22; 95%CI 1.61-11.02 p=0.001). FDG remained prognostic when G3 tumors were excluded (N=148) (HR 3.52; 95%CI 1.32-9.42 p= 0.007). When analyzing dual tracer PET imaging, patients with DOTA+/FDG- had reduced risk of dying in comparison with DOTA+/FDG+ (HR:0.26; 95%CI 0.09-0.67 p=0.01). After multivariate analysis, FDG positivity remained independently associated with reduced survival (HR 2.87; 95%CI 1.06-7.75 p=0.04) when controlling for grade of tumor and age. Conclusions: In this prospective cohort of metastatic GEPNENs, a positive FDG PET was significantly associated with reduced overall survival. These results provide additional evidence to support dual tracer functional imaging use in metastatic well differentiated GEPNEN’s. [Table: see text]

Retraction of "Activated Microglia in the Early Stage of a Rat Model of Parkinson's Disease: Revealed by PET-MRI Imaging by [18F]DPA-714 Targeting TSPO".

In the past decades, translocator protein (TSPO) has been considered as an in vivo biomarker to measure the presence of neuroinflammatory reactions. In this study, expression of TSPO was quantified via [18F]DPA-714 positron emission tomography-magnetic resonance imaging (PET-MRI) imaging to investigate the effects of microglial activation associated with motor behavioral impairments in the 6-hydroxydopamine (6-OHDA)-treated rodent model of Parkinson's disease (PD). [18F]FDG PET-MRI (for non-specific inflammation), [18F]D6-FP-(+)-DTBZ PET-MRI (for damaged dopaminergic neurons), post-PET immunofluorescence, and Pearson's correlation analyses were also performed. The time course of the striatal [18F]DPA-714 binding ratio elevated in 6-OHDA-treated rats during 1-3 weeks post-treatment, with the peak TSPO binding in the 1st week. No differences between bilateral striatum in [18F]FDG PET imaging were found. Moreover, an obvious correlation between [18F]DPA-714 SUVRR/L and rotation numbers was found (r = 0.434, *p = 0.049). No correlation between [18F]FDG SUVRR/L and rotation behavior was found. [18F]DPA-714 appeared to be a potential PET tracer for imaging the microglia-mediated neuroinflammation in the early stage of PD.

Activated Microglia in the Early Stage of a Rat Model of Parkinson's Disease: Revealed by PET-MRI Imaging by [18F]DPA-714 Targeting TSPO.

In the past decades, translocator protein (TSPO) has been considered as an in vivo biomarker to measure the presence of neuroinflammatory reactions. In this study, expression of TSPO was quantified via [18F]DPA-714 positron emission tomography-magnetic resonance imaging (PET-MRI) to investigate the effects of microglial activation associated with motor behavioral impairments in the 6-hydroxydopamine (6-OHDA)-treated rodent model of Parkinson's disease (PD). [18F]FDG PET-MRI (for non-specific inflammation), [18F]D6-FP-(+)-DTBZ PET-MRI (for damaged dopaminergic (DA) neurons), post-PET immunofluorescence, and Pearson's correlation analyses were also performed. The time course of striatal [18F]DPA-714 binding ratio was elevated in 6-OHDA-treated rats during 1-3 weeks post-treatments, with peak TSPO binding in the 1st week. No difference between the bilateral striatum in [18F]FDG PET imaging were found. Moreover, an obvious correlation between [18F]DPA-714 SUVRR/L and rotation numbers was found (r = 0.434, *p = 0.049). No correlation between [18F]FDG SUVRR/L and rotation behavior was found. [18F]DPA-714 appeared to be a potential PET tracer for imaging the microglia-mediated neuroinflammation in the early stage of PD.

Preclinical evaluation of 2-[18F]fluorodeoxysorbitol as a tracer for targeted imaging of Enterobacterales infection

Fluorine-18-fluorodeoxyglucose ([18F]FDG) positron emission tomography (18F-FDG-PET) is widely used for the detection of inflammatory and infectious diseases. Although this modality has proven to be a useful diagnostic tool, reliable distinction of bacterial infection from sterile inflammation or even from a malignancy remains challenging. Therefore, there is a need for bacteria-specific tracers for PET imaging that facilitate a reliable distinction of bacterial infection from other pathology. The present study was aimed at exploring the potential of 2-[18F]-fluorodeoxysorbitol ([18F]FDS) as a tracer for detection of Enterobacterales infections. Sorbitol is a sugar alcohol that is commonly metabolized by bacteria of the Enterobacterales order, but not by mammalian cells, which makes it an attractive candidate for targeted bacterial imaging. The latter is important in view of the serious clinical implications of infections caused by Enterobacterales. Here we demonstrate that sorbitol-based PET can be applied to detect a broad range of clinical bacterial isolates not only in vitro, but also in blood and ascites samples from patients suffering from Enterobacterales infections. Notably, the possible application of [18F]FDS is not limited to Enterobacterales since Pseudomonas aeruginosa and Corynebacterium jeikeium also showed substantial uptake of this tracer. We conclude that [18F]FDS is a promising tracer for PET-imaging of infections caused by a group of bacteria that can cause serious invasive disease.

Abstract P2-03-25: Pilot study to evaluate circulating tumor DNA (ctDNA) to PET/CT imaging using 18F-Fluorodeoxyglucose (FDG) and 18F-Fluoroestradiol (FES) PET/CT imaging as biomarkers in patients with metastatic breast cancer

Abstract Background: 18F-FES is an FDA-approved estrogen analogue PET imaging tracer (Cerianna) which measures tumor estrogen receptor (ER) expression at multiple tumor sites simultaneously and predicts response to endocrine therapy. 18F-FDG is a commonly used glucose PET imaging tracer which measures glycolytic metabolic activity in tumors. Elevated plasma ctDNA has been associated with an increased risk of relapse and can identify actionable genomic alterations. This pilot research study explored the relationship between somatic copy-number variants (CNVs) and cell-free DNA mass using low-pass-whole-genome (LPWG) ctDNA in the blood to FES and FDG PET/CT findings with both qualitative and quantitative image analysis in metastatic breast cancer patients. Methods: Two(2) 10ml Streck tubes were collected from 20 patients with metastatic ER+ breast cancer +/-30 days of their FDG-PET/CT scan (n=19) or their FES-PET/CT scan (n=9). 8 patients had both scans. Somatic mutations were assessed using comprehensive genomic profiling of tissue samples from 19 patients using the clinically validated UW-Oncoplex assay. Qualitative analysis included detection of LPWG ctDNA, presence of PIK3A mutations in tissue, and intensity of uptake in PET/CT imaging. LPWG ctDNA of blood samples evaluated ctDNA mass and CNVs that comprised at least 8% of total ctDNA. Total lesion glycolysis (TLG) in FDG scans and total lesion estrogen receptors (TLER) in FES scans were calculated using a dedicated workflow in MiM software (MiM Software Inc. Cleveland OH). Quantitative analysis included the circulating fraction (ctDNA), PET/CT SUVmax of the index lesion, number of lesions, TLG and TLER. For TLG, the threshold for determining measurable lesions was calculated using liver SULmean + 1.5*SD. The threshold for TLER was calculated using SUVmean of the mediastinal blood pool. The ctDNA fraction and the number of lesions for both FDG and FES were each ranked into 3 categories. FDG and FES data (SUVmax of index lesion, # of lesions, and TLG or TLER) were correlated to the calculated ctDNA fraction values. TLG and TLER were also correlated to each other. Results: ctDNA was classified as no ctDNA present (n=9), ctDNA present (n=8) and indeterminate (n=3). Average neoplastic ctDNA fraction was 0.114 (range 0.03-0.423). PIKC3A mutations were: 10 absent and 9 present. Ranked categories for ctDNA fraction, FDG TLG and FES TLER are shown in Table 1. Table 2 shows results of FDG and FES analysis and correlation with ctDNA. Ranked ctDNA findings correlated with both the FDG number of lesions (R2=0.69) and TLG (R2=0.83), but not the SUVmax of the index lesion (R2=0.29). Correlation decreased for ctDNA versus FES number of lesions (R2=0.51), TLER (R2=0.61), and SUVmax of index lesion (R2=0.16). TLG and TLER significantly correlated with the 8 patients that had both an FDG and FES PET/CT scan (R2=0.77). Conclusions: In this pilot study, FDG TLG showed a significant correlation with ctDNA. There is an encouraging association with ctDNA fraction and number of FDG lesions and with ctDNA fraction and extent of FES avid disease (TLER) in the 9 patients that had FES. Research Support: RG1005258 Table 1. Categorical rankings for qualitative analysis of ctDNA, TLG and TLER Table 2. FDG and FES imaging results and correlation with ctDNA Citation Format: Natasha Hunter, Lanell M. Peterson, Mark Muzi, Eric Q. Konnick, Jonathan Reichel, Paul Kinahan, Jennifer M. Specht, Rachel Yung, William R. Gwin, Hannah Linden, Christina Tran. Pilot study to evaluate circulating tumor DNA (ctDNA) to PET/CT imaging using 18F-Fluorodeoxyglucose (FDG) and 18F-Fluoroestradiol (FES) PET/CT imaging as biomarkers in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-25.

Abstract P2-03-17: Fluoroestradiol (FES) and Fluorodeoxyglucose (FDG) PET imaging in patients with ER+, HER2+ or HER2- metastatic breast cancer

Abstract Background: 18F-Fluorodeoxyglucose (FDG) has long been used for measuring tumor glycolytic activity in clinical PET imaging. The FDA recently approved 18F-Fluoroestradiol (FES) (Cerianna) as a PET imaging tracer for characterizing disease in patients with estrogen-receptor positive (ER+) breast cancer. As FES PET enters clinical practice it is important to establish its utility in the full population of hormone-receptor positive patients, including for patients with human epidermal growth factor 2 (HER2)-overexpressing tumors. Patients with HER2-positive metastatic breast cancer have historically been treated with combination cytotoxic and HER2-directed therapy, with the understanding that HER2 is the primary driver in this disease state. This retrospective study examined uptake in matched lesions for both FES and FDG PET and compared activity in patients with HER2 positive versus HER2 negative metastatic breast cancer. Methods: Patients were selected from the UW research database who had a history of biopsy-proven primary ER+ breast cancer as well as FES and FDG PET scans within 30 days. We examined FDG and FES scans and recorded SUVmax in up to 16 matched lesions between the two scans. Patients were also divided by HER2 status (+/-). In addition, a subset of patients who underwent at least 2 paired FDG and FES scans were reviewed. Results: 270 matched FDG and FES scans were analyzed in 216 patients with history of ER+, and HER2+ or HER2- breast cancer who were not part of an ongoing clinical trial. 158 (73%) had ductal disease, 38 (18%) had lobular disease. 183 (85%) had HER2- breast cancer. Of the 33 patients who had HER2+ breast cancer, 28 (85%) had ductal carcinoma. 40 patients underwent serial scans, allowing tracking over multiple timepoints. A total of 1323 metastatic sites were recorded (average = 5/scan (range 1,16)), with the majority (71%) representing bony lesions. No difference in quantitative FES or FDG avidity was observed between soft tissue and osseous sites. FES and FDG SUVmax were similar among patients with either HER2- or HER2+ breast cancer (Table 1). Among 40 patients with multiple paired FDG and FES scans, 26 (65%) had 2 scans while the remaining 14 had 3, with FES avidity remaining stable over time. There was no correlation between FES or FDG scans and HER2 status. Conclusion: In a cohort of ER+, HER2+ and HER2- patients undergoing concurrent FDG and FES PET scans, FDG and FES activity was similar regardless of HER2 status. FES uptake in both HER2- and HER2+ patients and stability over time in serial scans suggest that HER2 does not affect ER density. This suggests that in many patients with so-called “triple positive” disease, endocrine therapy may offer a powerful primary rather than ancillary tool in select patients. FES combined with FDG PET may offer utility in predicting and assessing response to therapy in this patient population. Table 1. FES and FDG uptake in patients with HER2- or HER2+ disease Citation Format: Natasha Hunter, Lanell M. Peterson, David A. Mankoff, Mark Muzi, Delphine Chen, William R. Gwin, Shaveta Vinayak, Nancy E Davidson, Jennifer M. Specht, Hannah Linden. Fluoroestradiol (FES) and Fluorodeoxyglucose (FDG) PET imaging in patients with ER+, HER2+ or HER2- metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-17.

Preliminary evaluation of a 64Cu-labeled DNA aptamer for PET imaging of glioblastoma

To develop a DNA aptamer-based PET tracer for imaging of glioblastoma. 5 mM of NOTA-AS1411, 60-min, and 37 °C were selected as the optimal condition for 64Cu radiolabeling of AS1411. 64Cu-NOTA-AS1411 remained stable in PBS and 100% mouse serum for at least six hours. From the PET images, 64Cu-NOTA-AS1411 tended to be excreted out through the kidneys and there was high tracer accumulation in the bladder. There was a higher tumor uptake in the AS1411 group than that in the control group. 64Cu-NOTA-AS1411 is a suitable potential PET tracer for imaging murine glioblastoma.

18F]TRACK, a PET tracer for imaging of tropomyosin receptor kinases (Trk): efficient radiosynthesis and preliminary evaluation in the TgF344‐AD rat model of Alzheimer’s disease.

AbstractBackgroundA family of tropomyosin receptor kinases (TrkA/B/C) plays important roles in the regulation of neuronal differentiation, growth, and survival via their interactions with neurotrophins. A growing body of literature suggests the downregulation of Trk in many neurodegenerative conditions of the central nervous system (CNS), including Alzheimer’s disease (AD). We recently reported the development of [18F]TRACK, the PET tracers for in vivo imaging of TrkB and its first in‐human study. Here, we wish to report a fully automated GMP‐compliant radiosynthesis of [18F]TRACK at high radiochemical purity (RCP) and molar activity and its preliminary evaluation in wild‐type and a transgenic rat model of AD.MethodRadiosynthesis was performed using Scintomics GRP automated module via copper‐catalyzed 18F‐fluorination of the chiral boron pinacolate precursor. Brain imaging in wild‐type (n = 3) and TgF344‐AD rat models (n = 2) at 23 months was performed on microPET Concord R4 scanner.Result[18F]TRACK was synthesized with a 5.0±1.4 % radiochemical yield not corrected for decay (activity range 95–154 mCi) with >99% RCP and molar activities of 250 ± 75 GBq/µmol (n = 6). The synthesis was fully automated and all batches passed quality control procedures, including chemical purity, sterility and pyrogenicity. The tracer showed moderate brain uptake in wild‐type rats with the highest accumulation in the thalamus (SUVmax = 1.56 ± 0.28, 10 min post‐injection), consistent with the brain regional distribution in humans acquired in a parallel study. Preliminary data suggests lower tracer uptake in TgF344‐AD rat model of AD in thalamus, striatum and frontal cortex compared to wild‐type animals.ConclusionThis study demonstrated the feasibility of the GMP‐compliant production of [18F]TRACK in sufficient doses and molar activities for scanning multiple subjects per day or long range deliveries. Preliminary biodistribution studies showed moderate brain uptake of the tracer with preferential accumulation in the thalamus across species. These findings warrants further studies of Trk brain expression and its implication in neurodegenerative and psychiatric pathologies using [18F]TRACK.

A practical fully automated radiosynthesis of [18F]Flurpiridaz on the module modular lab-pharmtracer without external purification

Background[18F]Flurpiridaz is a promising novel cardiac PET imaging tracer formed by the radiolabeling of pyridaben derivative with fluorine-18. Clinical studies on [18F]Flurpiridaz are currently at the phase III level for the assessment of MPI. Providing high image quality thanks to its relatively long half-life, F-18 is a high-potential radionuclide for the early detection of CAD. In this study, we aimed to develop a fully automated synthesis of [18F]Flurpiridaz without further preparative HPLC purification.ResultsPrecursor 6 was obtained by multi-step synthesis starting from mucochloric acid (1) as a sole product with 35% yield and identified by spectroscopic measurement. Manually cold labeling experiments were performed using the stable isotope [19F]F, and TBA-HCO3 PTC provided desirable fluorinated compound with high yield. A fully automated [18F]Flurpiridaz synthesis on the ML-PT device provided 55–65% radiochemical yield with more than 98% radiochemical purity. The final product purification method demonstrated that [18F]Flurpiridaz could be obtained without an external preparative HPLC system as a pharmaceutical quality.ConclusionA novel and fascinating strategy was developed for the fully automated synthesis of [18F]Flurpiridaz (7) on ML PT. Organic synthesis of precursor 6 was achieved with a desirable yield and characterized by NMR and HR-MS. A detailed set of cold experiments were completed for optimization conditions before hot trials and TBA-HCO3 increased molar activity with a minimum amount of side products. Radiolabeling showed that our self-designed automated synthesis method enables high radiochemical yield and radiochemical purity for the production of [18F]Flurpiridaz. The desirable radiopharmaceutical quality of the product was obtained without using an additional preparative HPLC system. [18F]Flurpiridaz (7) preserved its stability within 12 h and final specifications were consistent with the acceptance criteria in Ph. Eur. regulations.

Discovery of a CSF-1R inhibitor and PET tracer for imaging of microglia and macrophages in the brain

Colony stimulating factor 1 receptor (CSF-1R) is a kinase expressed on macrophages and microglia in the brain. It has been recognized as a potential drug and imaging target in treatment of neuroinflammatory diseases and glioblastoma. Despite several attempts, no validated CSF-1R PET tracer is currently available. The aim of this work was to develop a brain permeable CSF-1R PET tracer for non-invasive imaging of CSF-1R in vivo. Based on fragments of two potent and selective CSF-1R inhibitors, novel hybrid molecules were designed and synthesized. Affinity for human recombinant CSF-1R and selectivity over c-KIT and PDGFR-β was determined using a FRET based in vitro assay. Radiosynthesis was performed by fully automated [11C]CH3I methylation of the corresponding des-methyl precursor. PET imaging was performed at baseline, efflux transporter blocking and CSF-1R blocking conditions. Moreover, tracer distribution and blood and plasma radiometabolites were determined following injection in healthy mice. The most promising CSF-1R inhibitor, compound 4, showed high selectivity and high affinity for CSF-1R (IC50: 12 ± 3 nM) and no affinity for kinase family members c-KIT and PDGFR-beta. [11C]4 was obtained in good yield (15 ± 0.2 % decay corrected yield, (2.0 ± 0.26 GBq at end of synthesis) and excellent purity. The compound demonstrated high brain penetration and good metabolic stability (>2 %ID/g at 60 min post injection and 79 ± 8 % intact [11C]4 in brain at 60 min post injection) and no strong efflux transporter substrate behavior. Blocking CSF-1R prior to imaging with [11C]4 resulted in significant decrease in brain uptake. In conclusion, [11C]4 shows good potential as a novel PET tracer for imaging of CSF-1R in the CNS and future experiments in relevant animal models are warranted.

Comparison of [18F]DOPA and [68Ga]DOTA-TOC as a PET imaging tracer before peptide receptor radionuclide therapy

BackgroundIn treatment of neuroendocrine neoplasms (NENs), confirmation of somatostatin receptor expression with 68Ga-DOTA somatostatin analogues is mandatory to determine eligibility for peptide receptor radionuclide therapy (PRRT). [18F]DOPA can detect additional lesions compared to [68Ga]DOTA-TOC. The aim of this study was to explore differences in tumour detection of both tracers and their relevance for selecting patients for PRRT. We retrospectively studied eight patients with NENs who underwent both [68Ga]DOTA-TOC and carbidopa-enhanced [18F]DOPA PET/CT, before first-time PRRT with [177Lu]DOTA-TATE. Tracer order was influenced due to stock availability or to detect suspected metastases with a second tracer. On CT, disease control was defined as a lesion showing complete response, partial response, or stable disease, according to RECIST 1.1. criteria.ResultsSeven patients with in total 89 lesions completed four infusions of 7.4 GBq [177Lu]DOTA-TATE, one patient received only two cycles. Before treatment, [18F]DOPA PET/CT detected significantly more lesions than [68Ga]DOTA-TOC PET/CT (79 vs. 62, p < .001). After treatment, no difference in number of lesions with disease control was found for [18F]DOPA-only (5/27) and [68Ga]DOTA-TOC-only lesions (4/10, p = .25). [18F]DOPA detected more liver metastases (24/27) compared to [68Ga]DOTA-TOC (7/10, p = .006). Six patients showed inpatient heterogeneity in treatment response between [18F]DOPA-only and [68Ga]DOTA-TOC-only lesions.ConclusionsResponse to PRRT with [177Lu]DOTA-TATE was comparable for both [68Ga]DOTA-TOC- and [18F]DOPA-only NEN lesions. [18F]DOPA may be capable of predicting response to PRRT while finding more lesions compared to [68Ga]DOTA-TOC, although these additional lesions are often small of size and undetected by diagnostic CT.

Matched FES and FDG PET imaging in patients with hormone receptor-positive, HER2+ advanced breast cancer.

1042 Background: The recently FDA approved 18F-Fluoroestradiol (FES) is a PET imaging tracer for characterizing disease in patients with ER+ breast cancer. As FES PET enters clinical practice it will be important to establish its utility in the full population of hormone-receptor positive patients, including those with HER2+ tumors. Historically the consensus around ER+/HER+ disease has been that these tumors are primarily driven by HER2, with therapies focused on targeting this pathway. Emerging research suggests that ER+ and HER2+ tumors represent a distinct phenotype, with bidirectional crosstalk between ER and HER2 pathways contributing to resistance to therapies targeting these critical pathways. Methods: Our cross-sectional database of patients with one or more FES scans stretches back to 1996. We selected all patients with HER2+ advanced breast cancer to determine whether ER is functional in the ER+/HER2+ subset. We examined paired FDG and FES scans and recorded SUVmax in matched lesions between the FDG and FES scans. We also looked at a subset of patients who underwent scans at more than one time-points and examined the clinical characteristics of these cases over time. Results: 36 patients with metastatic ER+, HER2+ breast cancer underwent concurrent FDG and FES PET scans between 1996 and 2013. 34 subjects (94%) were female; 32 (89%) were Caucasian, and 4 (11%) were Asian. Eight patients underwent serial scans. A total of 200 metastatic sites were recorded with the majority (67%) being bony lesions. No difference in quantitative FES avidity was observed between soft tissue and osseous sites. Six patients (16%) had negative FES scans despite displaying FDG avid lesions; three patients had at least one negative FES scan on serial scans, and two demonstrated FES-avid lesions with no FDG activity. Average FES SUVmax for positive scans was 3.5, with a range of 0.8 to 10.7. Among eight patients with multiple scans, half had 2 scans, three had 3 scans, and one had 4 scans. In 7/8 patients (88%) FES avidity increased over time even as FDG decreased or stayed stable with treatment; in one, both FES and FDG decreased on follow up scan. Conclusions: In a cohort of ER+, HER2+ patients undergoing FDG and FES PET scans, robust concordance between FDG and FES uptake was observed. FES avidity increased in patients with multiple scans, suggesting that the ER pathway remained active during treatment. The strong FES positivity in many HER2+ patients in this cohort suggests that FES PET could be used to guide patient selection for trials examining deescalated regimens employing a non-chemotherapy partner for HER2-directed therapy or emphasizing more ER-directed therapies such as CDK4/6 inhibitors, which are not currently approved in this population. With the ongoing development of HER2- PET imaging, combination scans could carry the potential for discrimination between sites, possibly serving as a tool to guide biopsy.

Development of [18F]AldoView as the first highly selective aldosterone synthase PET tracer for imaging of patients with primary hyperaldosteronism

Development of [18F]AldoView as the first highly selective aldosterone synthase PET tracer for imaging of patients with primary hyperaldosteronism

P-253 - Development of 18F-labeled tracer for noninvasive PET imaging of the STING expression in tumor microenvironment

P-253 - Development of 18F-labeled tracer for noninvasive PET imaging of the STING expression in tumor microenvironment

MP51-15 THE ROLE OF 68 GA-PSMA- AND 68 GA-DOTA-RM2 PET/MRI IN THE PRIMARY STAGING OF HIGH-RISK PROSTATE CANCER PATIENTS UNDERGOING RADICAL PROSTATECTOMY. PRELIMINARY RESULTS OF A PROSPECTIVE, SINGLE CENTER STUDY

MP51-15 THE ROLE OF ⁶⁸ GA-PSMA- AND ⁶⁸ GA-DOTA-RM2 PET/MRI IN THE PRIMARY STAGING OF HIGH-RISK PROSTATE CANCER PATIENTS UNDERGOING RADICAL PROSTATECTOMY. PRELIMINARY RESULTS OF A PROSPECTIVE, SINGLE CENTER STUDY

P-043 - Synthesis of PET tracers for imaging of thiocyanate efflux from the brain

P-043 - Synthesis of PET tracers for imaging of thiocyanate efflux from the brain

P-106 - A novel fluorine-18 labeled P2Y12 receptor PET tracer for imaging of anti-inflammatory microglia

P-106 - A novel fluorine-18 labeled P2Y12 receptor PET tracer for imaging of anti-inflammatory microglia

Recent development in selective Tau tracers for PET imaging in the brain

Abnormal Tau deposition is a crucial pathological hallmark of various neurodegenerative disorders defined as tauopathies, of which Alzheimer's disease is the most prominent one. To date, a large number of chemical entities with different structures have been developed as Tau imaging tracers for the early diagnosis of tauopathies. Several of them with excellent bio-properties are currently being assessed in clinical trials, and more recently, the Tauvid™ ([18F]Flortaucipir, also known as [18F]AV1451 or [18F]T807) as the first Tau tracer was approved by the U.S. Food and Drug Administration in 2020. This review summarized the latest development of Tau tracers and analyzed their chemical structures, with particular attention to the effects of chemical structures on biological properties. In addition, we also discuss the limitations of current Tau imaging tracers, issues that need attention in the development of new tracers, and possible future directions.

Direct Reconstruction of Linear Parametric Images From Dynamic PET Using Nonlocal Deep Image Prior.

Direct reconstruction methods have been developed to estimate parametric images directly from the measured PET sinograms by combining the PET imaging model and tracer kinetics in an integrated framework. Due to limited counts received, signal-to-noise-ratio (SNR) and resolution of parametric images produced by direct reconstruction frameworks are still limited. Recently supervised deep learning methods have been successfully applied to medical imaging denoising/reconstruction when large number of high-quality training labels are available. For static PET imaging, high-quality training labels can be acquired by extending the scanning time. However, this is not feasible for dynamic PET imaging, where the scanning time is already long enough. In this work, we proposed an unsupervised deep learning framework for direct parametric reconstruction from dynamic PET, which was tested on the Patlak model and the relative equilibrium Logan model. The training objective function was based on the PET statistical model. The patient's anatomical prior image, which is readily available from PET/CT or PET/MR scans, was supplied as the network input to provide a manifold constraint, and also utilized to construct a kernel layer to perform non-local feature denoising. The linear kinetic model was embedded in the network structure as a 1 ×1 ×1 convolution layer. Evaluations based on dynamic datasets of 18F-FDG and 11C-PiB tracers show that the proposed framework can outperform the traditional and the kernel method-based direct reconstruction methods.