Whole-body PET Scans Research Articles

Rosai-Dorfman-Destombes disease in adolescence with hearing and vision loss involvement: A multidisciplinary approach.

Purpose. To report a rare case of Rosai-Dorfman-Destombes (RDD) disease in a teenage girl exhibiting mild fever, night chills, vertigo, and progressive bilateral vision and hearing loss. Method. Case report of a 15-year-old girl who underwent extensive ophthalmic multimodal imaging and a comprehensive workup evaluation. Results. Multiple choroid lesion masses in both eyes associated with systemic multifocal lymphadenopathy, involvement of the paranasal sinuses, and unusual intracranial manifestations well-shown by magnetic resonance imaging (MRI) and whole-body PET-scan. The PET-Scan and MRI imaging showed dural-based intracranial lesions, choroid-plexus signaling, and meningeal spread, as well as a focus on the paranasal sinuses, which helped determine the best biopsy location for a definitive diagnosis through immunohistochemistry. Conclusions. Here we describe a rare condition of RDD disease with bilateral visual and hearing loss associated with bilateral multiple choroid masses and neurological symptoms in an adolescent female patient. A definitive diagnosis relied on histological assessment, emphasizing the importance of interdisciplinary evaluation. RDD should be considered in the differential diagnosis of choroidal metastasis, tuberculosis, and other lymphoproliferative diseases.

PETcoil: first results from a second-generation RF-penetrable TOF-PET brain insert for simultaneous PET/MRI

Simultaneous positron emission tomography (PET)/magnetic resonance imaging provides concurrent information about anatomic, functional, and molecular changes in disease. We are developing a second generation MR-compatible RF-penetrable TOF-PET insert. The insert has a smaller scintillation crystal size and ring diameter compared to clinical whole-body PET scanners, resulting in higher spatial resolution and sensitivity. This paper reports the initial system performance of this full-ring PET insert. The global photopeak energy resolution and global coincidence time resolution, 11.74 ± 0.03 % FWHM and 238.1 ± 0.5 ps FWHM, respectively, are preserved as we scaled up the system to a full ring comprising 12, 288 LYSO-SiPM channels (crystal size: 3.2 × 3.2 × 20 mm3). Throughout a ten-hour experiment, the system performance remained stable, exhibiting a less than 1% change in all measured parameters. In a resolution phantom study, the system successfully resolved all 2.8 mm diameter rods, achieving an average VPR of 0.28 ± 0.08 without TOF and 0.24 ± 0.07 with TOF applied. Moreover, the implementation of TOF in the Hoffman phantom study also enhanced image quality. Initial MR compatibility studies of the full PET ring were performed with it unpowered as a milestone to focus on looking for material and geometry-related artifacts. During all MR studies, the MR body coil functioned as both the transmit and receive coil, and no observable artifacts were detected. As expected, using the body coil also as the RF receiver, MR image signal-to-noise ratio exhibited degradation (∼30%), so we are developing a high quality receive-only coil that resides inside the PET ring.

Utility of PET-CT for assessment of response to neo-adjuvant chemotherapy in breast cancer.

12 Background: Response to neo-adjuvant chemotherapy (NACT) is associated with prognosis in non-metastatic breast cancer and can potentially inform further therapeutic options. The aim of this study was to correlate post NACT response on PET CT with pathological response. Methods: All patients who underwent pre- NACT (baseline) and post NACT PET CT imaging with F-18 FDG in a dose of 5-7 MBq/kg body weight with a minimum of 185 MBq given intravenously were retrospectively analyzed. Scan was performed on GE Discovery 710 whole-body PET scan with 128 slice CT. Relevant clinical and imaging related details were extracted from the treatment records. Post NACT PET response (PERCIST criteria) in the primary tumor and nodes was correlated with the pathological response on the post surgical specimen. Analysis was done using Microsoft Excel and SPSS v20 (IBM SPSS). Results: The median age was 49 years (range 30-76 years). 83.1% of patients had node positive disease on baseline PET imaging (not pathologically confirmed). Post chemotherapy PET showed complete metabolic response in the primary tumor and regional nodes in 56.3% and 74% of patients respectively. Two patients had progressive local disease. Pathological complete response rates post surgery in triple negative, Her2 neu positive and ER positive group was 50%, 34% and 12% respectively. The sensitivity, specificity, positive predictive value and negative predictive value is tabulated below. Conclusions: Overall FDG PET CT showed good specificity with limited sensitivity for post NACT response assessment in breast cancer. Our results suggest that post NACT PET CT may have limited utility for clinical decision making and at present its use cannot be recommended outside of a clinical trial.[Table: see text]

First-in-human evaluation of 6-bromo-7-[11C]methylpurine, a PET tracer for assessing the function of multidrug resistance-associated proteins in different tissues

PurposeMultidrug resistance-associated protein 1 (MRP1) is a transport protein with a widespread tissue distribution, which has been implicated in the pathophysiology of Alzheimer’s and chronic respiratory disease. PET with 6-bromo-7-[11C]methylpurine ([11C]BMP) has been used to measure MRP1 function in rodents. In this study, [11C]BMP was for the first time characterised in humans to assess the function of MRP1 and other MRP subtypes in different tissues.MethodsThirteen healthy volunteers (7 men, 6 women) underwent dynamic whole-body PET scans on a long axial field-of-view (LAFOV) PET/CT system after intravenous injection of [11C]BMP. Three subjects of each sex were scanned a second time to assess reproducibility. Volumes of interest were outlined for MRP-expressing tissues (cerebral cortex, cerebellum, choroid plexus, retina, lungs, myocardium, kidneys, and liver). From the time-activity curves, the elimination rate constant (kE, h− 1) was derived as a parameter for tissue MRP function and its test-retest variability (TRTV, %) was calculated. Radiation dosimetry was calculated using the Medical Internal Radiation Dose (MIRD) methodology.ResultsMean kE and corresponding TRTV values were: cerebral cortex: 0.055 ± 0.010 h− 1 (− 4 ± 24%), cerebellum: 0.033 ± 0.009 h− 1 (1 ± 39%), choroid plexus: 0.292 ± 0.059 h− 1 (0.1 ± 16%), retina: 0.234 ± 0.045 h− 1 (30 ± 38%), lungs: 0.875 ± 0.095 h− 1 (− 3 ± 11%), myocardium: 0.641 ± 0.105 h− 1 (11 ± 25%), kidneys: 1.378 ± 0.266 h− 1 (14 ± 16%), and liver: 0.685 ± 0.072 h− 1 (7 ± 9%). Significant sex differences were found for kE in the cerebellum, lungs and kidneys. Effective dose was 4.67 ± 0.18 µSv/MBq for men and 4.55 ± 0.18 µSv/MBq for women.ConclusionLAFOV PET/CT with [11C]BMP potentially allows for simultaneous assessment of MRP function in multiple human tissues. Mean TRTV of kE in different tissues was in an acceptable range, except for the retina. The radiation dosimetry of [11C]BMP was in the typical range of 11C-tracers. LAFOV PET/CT holds great potential to assess at a whole-body, multi-tissue level molecular targets relevant for drug disposition in humans.Trial registrationEudraCT 2021-006348-29. Registered 15 December 2021.

Eyes on the unseen-lung adenocarcinoma presenting as iris and ciliary body metastases: A case report

A 65-year-old male was referred for a left-eye irido-ciliary body mass for further evaluation. In the left eye, there was a small, well-circumscribed, white gelatinous, amelanotic mass noted temporally in the angle with a filiform appearance. The ultrasound biomicroscopy showed a large hyperreflective mass at 3 o’clock in the ciliary body, the anterior chamber, angle, iris, and anterior surface of the lens. Iris tissue biopsy was done, and the sample was sent for histopathology with immunohistochemistry. The histopathological examination identified the tumor composed of malignant cells forming glandular structures alongside papillary projections. Immunohistochemical tests showed positive results for CK (AE1/AE3). The diagnosis of a poorly differentiated adenocarcinoma was made. A whole-body PET scan and CT scan were done. The imaging features were suggestive of primary bronchogenic malignancy of the right lung with systemic metastases. The lung biopsy confirmed the diagnosis. Iridociliary mass warrants a detailed evaluation for appropriate management by a multidisciplinary team.

Multicenter PET image harmonization using generative adversarial networks

PurposeTo improve reproducibility and predictive performance of PET radiomic features in multicentric studies by cycle-consistent generative adversarial network (GAN) harmonization approaches.MethodsGAN-harmonization was developed to harmonize whole-body PET scans to perform image style and texture translation between different centers and scanners. GAN-harmonization was evaluated by application to two retrospectively collected open datasets and different tasks. First, GAN-harmonization was performed on a dual-center lung cancer cohort (127 female, 138 male) where the reproducibility of radiomic features in healthy liver tissue was evaluated. Second, GAN-harmonization was applied to a head and neck cancer cohort (43 female, 154 male) acquired from three centers. Here, the clinical impact of GAN-harmonization was analyzed by predicting the development of distant metastases using a logistic regression model incorporating first-order statistics and texture features from baseline 18F-FDG PET before and after harmonization.ResultsImage quality remained high (structural similarity: left kidney ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 0.800, right kidney ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 0.806, liver ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 0.780, lung ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 0.838, spleen ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 0.793, whole-body ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 0.832) after image harmonization across all utilized datasets. Using GAN-harmonization, inter-site reproducibility of radiomic features in healthy liver tissue increased at least by ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 5 ± 14% (first-order), ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 16 ± 7% (GLCM), ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 19 ± 5% (GLRLM), ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 16 ± 8% (GLSZM), ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 17 ± 6% (GLDM), and ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 23 ± 14% (NGTDM). In the head and neck cancer cohort, the outcome prediction improved from AUC 0.68 (95% CI 0.66–0.71) to AUC 0.73 (0.71–0.75) by application of GAN-harmonization.ConclusionsGANs are capable of performing image harmonization and increase reproducibility and predictive performance of radiomic features derived from different centers and scanners.

3-[18F]Fluoro-para-hydroxyphenethylguanidine (3-[18F]pHPG) PET-A Novel Imaging Modality for Paraganglioma.

Functional positron emission tomography (PET) imaging for the characterization of pheochromocytoma and paraganglioma (PCC/PGL) and for detection of metastases in malignant disease, offers valuable clinical insights that can significantly guide patient treatment. This work aimed to evaluate a novel PET radiotracer, 3-[18F]fluoro-para-hydroxyphenethylguanidine (3-[18F]pHPG), a norepinephrine analogue, for its ability to localize PCC/PGL. 3-[18F]pHPG PET/CT whole-body scans were performed on 16 patients (8 male:8 female; mean age 47.6 ± 17.6 years; range, 19-74 years) with pathologically confirmed or clinically diagnosed PCC/PGL. After intravenous administration of 304 to 475 MBq (8.2-12.8 mCi) of 3-[18F]pHPG, whole-body PET scans were performed at 90 minutes in all patients. 3-[18F]pHPG PET was interpreted for abnormal findings consistent with primary tumor or metastasis, and biodistribution in normal organs recorded. Standardized uptake value (SUV) measurements were obtained for target lesions and physiological organ distributions. 3-[18F]pHPG PET showed high radiotracer uptake and trapping in primary tumors, and metastatic tumor lesions that included bone, lymph nodes, and other solid organ sites. Physiological biodistribution was universally present in salivary glands (parotid, submandibular, sublingual), thyroid, heart, liver, adrenals, kidneys, and bladder. Comparison [68Ga]DOTATATE PET/CT was available in 10 patients and in all cases showed concordant distribution. Comparison [123I]meta-iodobenzylguanidine [123I]mIBG planar scintigraphy and SPECT/CT scans were available for 4 patients, with 3-[18F]pHPG showing a greater number of metastatic lesions. We found the kinetic profile of 3-[18F]pHPG PET affords high activity retention within benign and metastatic PCC/PGL. Therefore, 3-[18F]pHPG PET imaging provides a novel modality for functional imaging and staging of malignant paraganglioma with advantages of high lesion affinity, whole-body coregistered computed tomography, and rapid same-day imaging.

Combined surgical and chemotherapy treatment for invasive primary urethral cancer: a case presentation

BackgroundThe European Association of Urology (EAU) defines primary urethral carcinoma (PUC) as a carcinoma that arises in the urethra without a previous diagnosis of carcinoma elsewhere in the urinary system. It is considered as a rare cancer, accounting for less than 1% of all malignant tumors and 5% of malignant tumors of the urinary system. The difficulty in diagnosis and its rarity can lead to delayed diagnosis and decreased survival. We think that a case report to be made in the literature for this rare disease with no consensus on treatment will contribute to disease management.Case presentationIn this article, we describe the diagnosis and treatment process of a 75-year-old patient who was diagnosed with primary urethral cancer and had urethral discharge and difficulty in urination. The biopsy result from the suspected hyperemic area in the urethra in cystourethroscopy was primary urethral cancer. Urethrectomy followed by urethroplasty was performed on the patient's 2-cm primary urethral cancerous tissue. In the postoperative first month, an F-18 FDG whole-body PET scan for oncological evaluation showed increased pathological F-18 FDG uptake in the periphery of the mass in the penile urethra and indistinguishable boundaries from the prostatic urethra. After this, adjuvant gemcitabine and carboplatin therapy was planned by the oncology team.ConclusionsBased on our outcome in this case, we believe that chemotherapy combined with surgery increases the chance of successful treatment in locally advanced urethral cancer.

Phase I, first-in-human study of XTR004, a novel 18F-labeled tracer for myocardial perfusion PET: Biodistribution, radiation dosimetry, pharmacokinetics, and safety after a single injection at rest

ObjectivesThis study assessed the imaging characteristics, pharmacokinetics and safety of XTR004, a novel 18F-labeled Positron Emission Tomography (PET) myocardial perfusion imaging tracer, after a single injection at rest in humans. MethodsEleven healthy subjects (eight men and three women) received intravenous XTR004 (239–290 megabecquerel [MBq]). Safety profiles were monitored on the dosing day and three follow-up visits. Multiple whole-body PET scans were conducted over 4.7 h to evaluate biodistribution and radiation dosimetry. Blood and urine samples collected for 7.25 h were metabolically corrected to characterize pharmacokinetics. ResultsIn the first 0–12 min PET images of ten subjects, liver (26.81 ± 4.01), kidney (11.43 ± 2.49), lung (6.75 ± 1.76), myocardium (4.72 ± 0.67) and spleen (3.1 ± 0.84) exhibited the highest percentage of the injected dose (%ID). Myocardial uptake of XTR004 in the myocardium initially reached 4.72 %ID and 7.06 g/mL, and negligibly changed within an hour (Δ: 7.20%, 5.95%). The metabolically corrected plasma peaked at 2.5 min (0.0013896 %ID/g) and halved at 45.2 min. Whole-body effective dose was 0.0165 millisievert (mSv)/MBq. Cumulative urine excretion was 8.18%. Treatment-related adverse events occurred in seven out of eleven subjects (63.6%), but no severe adverse event was reported. ConclusionsXTR004 demonstrated a favorable safety profile, rapid, high, and stable myocardial uptake and excellent potential for PET myocardial perfusion imaging (MPI). Further exploration of XTR004 PET MPI for detecting myocardial ischemia is warranted.

SMARCB1-Deficient Skull Base Chondrosarcoma with 12p Duplication Presenting as Somatic-Type Malignancy Arising from Metastatic Seminoma

Somatic-type malignancy (STM) can occur infrequently within a primary or metastatic testicular germ cell tumor (TGCT) and is associated with dismal prognosis and survival. STM with chondrosarcomatous features is exceedingly rare and head and neck involvement has not been previously documented. A 39-year-old white man presented with nasal obstruction and epistaxis. Imaging disclosed a 6.9-cm expansile tumor involving the nasal cavity and skull base with intraorbital and intracranial extension. The histopathologic properties of the tumor were compatible with chondrosarcoma, grade II-III. Immunohistochemically, malignant cells were strongly and diffusely positive for S100 and epithelial markers, and showed loss of SMARCB1 expression. IDH1/2 mutations were not detected. Following whole-body PET scan, a 7.0-cm left testicular mass was discovered and diagnosed as seminoma with syncytiotrophoblastic cells, stage pT3NXM1b. Extensive retroperitoneal, mediastinal, and supraclavicular lymphadenopathy was also noticed. Histopathologic examination of the left supraclavicular lymph node revealed metastatic seminoma. By FISH, most metastatic nodal seminoma cells harbored 1 to 4 copies of isochromosome 12p, while the chondrosarcoma featured duplication of 12p. Presence of a malignant TGCT with disseminated supradiaphragmatic lymphadenopathy, the unique immunophenotypic properties of the skull-based chondrosarcoma and lack of IDH1/2 aberrations with gain of 12p strongly support the diagnosis of STM chondrosarcoma arising from metastatic TGCT. The patient did not respond to chemotherapy and succumbed three months after diagnosis. Although exceedingly uncommon, metastasis to the head and neck may occur in patients with TGCT. This case of STM chondrosarcoma demonstrated divergent immunophenotypic and molecular characteristics compared to “typical” examples of head and neck chondrosarcoma. High index of suspicion is advised regarding the diagnosis of lesions that present with otherwise typical histomorphology but unexpected immunohistochemical or molecular features.

Role of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography in restaging of adrenocortical carcinoma.

The objective was to retrospectively evaluate the contribution of fluorodeoxyglucose [18F] positron emission tomography/computed tomography (18FDG-PET/CT) to the re-staging of adrenocortical carcinoma (ACC). A total of 16 patients (10 males and 6 females), who underwent adrenalectomy due to adrenocortical carcinoma and 18FDG-PET/CT scan to re-stage the tumor between July 2007 and April 2013, were included in the present study. The mean age was 53.37 ± 13.91 years (min: 30, max: 74) The patients were required to fast for six hours prior to scanning, and whole-body PET scanning from the skull base to the upper thighs was performed approximately 1 h after the intravenous injection of 555 MBq of F-18 FDG. Whole body CT scanning was performed in the cranio-caudal direction. FDG-PET images were reconstructed using CT data for attenuation correction. Suspicious recurrent or metastatic lesions were confirmed by histopathology or clinical follow-up. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18FDG-PET/CT were 100%, 83.3%, 90.9%, 83.3%, and 93.7%, respectively. 18FDG-PET/CT detects local recurrence and/or distant metastases with high accuracy in the re-staging of operated adrenocortical carcinoma. It is considered that the procedure could play an important role in treatment decision after the operation and post-operative follow-up and could influence the entire decision-making process.

2412. Whole-body PET scans for infective endocarditis: differences in patient characteristics and outcomes

Abstract Background Whole-body 18F-FDG PET/CT (WBP) has the potential to impact management of infective endocarditis (IE) through identification of areas of occult primary or metastatic infection. This study compares the characteristics and outcomes in groups of patients with IE who did and did not have WBP as part of their evaluation to help guide how this imaging may be optimally utilized. Methods We performed a retrospective cohort study of hospitalized patients discussed at the multidisciplinary endocarditis meeting at a tertiary care center in Michigan, USA between June 2018 and January 2022. Protocolized chart review was performed by three study team members. Results There were 114 (26.7%) patients with suspected IE who had WBP and 313 (73.3%) who did not. The two groups were similar in age, gender, and race. Patients with ESRD on dialysis (p=0.01), cardiac and/or ascending aortic prosthetic material (p< 0.001) or endocardial devices (p=0.01), and those who had cardiac PET (P< 0.001) were more likely to have undergone WBP. Complications such as paravalvular abscess (p=0.004) and flail leaflet (p=0.01) were more common in the non-WBP group. There was no difference in surgical indication between groups, though the WBP group had a non-significant trend of not receiving cardiac surgery (p = 0.05). WBP was associated with a longer-course of antibiotics (6.36 vs 5.32; p< 0.001) and suppressive antibiotics (30.70% versus 13.42%; p< 0.001). Within the WBP group, 45.61% had a change in management after imaging with the most common changes being further infectious (20.18%) or non-infectious (9.65%) workup, source control procedure performed (10.52%), and antibiotic regimen change (9.64%). No other outcomes between groups were significantly different between groups including length of stay, 6-month readmission, 6-month infection relapse, 6-month mortality or in-hospital mortality. Conclusion Although a mortality benefit was not observed, WBP played an important role in the management of patients with IE with identification of areas of metastatic infection that required longer antimicrobial treatment or addition of suppressive antimicrobials. Further analyses are planned to understand which patients with IE may benefit most from WBP. Disclosures All Authors: No reported disclosures

The First Human Application of an F-18-Labeled Tryptophan Analog for PET Imaging of Cancer.

Preclinical studies showed the tryptophan analog PET radiotracer 1-(2-18F-fluoroethyl)-L-tryptophan (18F-FETrp) to accumulate in various tumors, including gliomas, and being metabolized via the immunosuppressive kynurenine pathway. In this first-in-human study, we tested the use 18F-FETrp-PET in patients with neuroendocrine and brain tumors. We applied dynamic brain imaging in patients with gliomas (n = 2) and multi-pass 3D whole-body PET scans in patients with neuroendocrine tumors (n =4). Semiquantitative analysis of organ and tumor tracer uptake was performed using standardized uptake values (SUVs). In addition, organ dosimetry was performed based on extracted time-activity curves and the OLINDA software. Neuroendocrine tumors showed an early peak (10-min post-injection) followed by washout. Both gliomas showed prolonged 18F-FETrp accumulation plateauing around 40 min and showing heterogeneous uptake including non-enhancing tumor regions. Biodistribution showed moderate liver uptake and fast clearance of radioactivity into the urinary bladder; the estimated effective doses were similar to other 18F-labeled radioligands. The study provides proof-of-principle data for the safety and potential clinical value of 18F-FETrp-PET for molecular imaging of human gliomas.

Visualization of small brain nuclei with a high-spatial resolution, clinically available whole-body PET scanner

ObjectiveTo verify the visibility of physiological 18F-fluorodeoxyglucose (18F-FDG) uptake in nuclei in and around the brainstem by a whole-body (WB) silicon photomultiplier positron emission tomography (SiPM-PET) scanner with point-spread function (PSF) reconstruction using various iteration numbers.MethodsTen healthy subjects (5 men, 5 women; mean age, 56.0 ± 5.0 years) who underwent 18F-FDG PET/CT using a WB SiPM-PET scanner and magnetic resonance imaging (MRI) of the brain including a spin-echo three-dimensional sampling perfection with application-optimized contrasts using different flip angle evolutions fluid-attenuated inversion recovery (3D-FLAIR) and a 3D-T1 magnetization-prepared rapid gradient-echo (T1-MPRAGE) images were enrolled. Each acquired PET image was reconstructed using ordered-subset expectation maximization (OSEM) with iteration numbers of 4, 16, 64, and 256 (subset 5 fixed) + time-of-flight (TOF) + PSF. The reconstructed PET images and 3D-FLAIR images for each subject were registered to individual T1-MPRAGE volumes using normalized mutual information criteria. For each MR-coregistered individual PET image, the pattern of FDG uptake in the inferior olivary nuclei (ION), dentate nuclei (DN), midbrain raphe nuclei (MRN), inferior colliculi (IC), mammillary bodies (MB), red nuclei (RN), subthalamic nuclei (STN), lateral geniculate nuclei (LGN), medial geniculate nuclei (MGN), and superior colliculi (SC) was visually classified into the following three categories: good, clearly distinguishable FDG accumulation; fair, obscure contour of FDG accumulation; poor, FDG accumulation indistinguishable from surrounding uptake.ResultsAmong individual 18F-FDG PET images with OSEM iterations of 4, 16, 64, and 256 + TOF + PSF, the iteration numbers that showed the best visibility in each structure were as follows: ION, MRN, LGN, MGN, and SC, iteration 64; DN, iteration 16; IC, iterations 16, 64, and 256; MB, iterations 64 and 256; and RN and STN, iterations 16 and 64, respectively. Of the four iterations, the 18F-FDG PET image of iteration 64 visualized FDG accumulation in small structures in and around the brainstem most clearly (good, 98 structures; fair, 2 structures).ConclusionsA clinically available WB SiPM-PET scanner is useful for visualizing physiological FDG uptake in small brain nuclei, using a sufficiently high number of iterations for OSEM with TOF and PSF reconstructions.

Abstract 17436: A Diagnostic Copycat: Culture Negative Endocarditis of A Bioprosthetic Valve Presenting as ANCA Vasculitis

A 59-year-old female with a history of bicuspid aortic valve (AV) complicated by aortic stenosis and ascending aortic aneurysm s/p bioprosthetic AV and ascending aorta replacement presented with a 6-month history of weight loss, fatigue, and lower extremity rash. Initial laboratory workup identified anemia, leukopenia, and acute kidney injury with proteinuria and microscopic hematuria. Further workup included negative blood cultures, elevated inflammatory markers, elevated rheumatoid factor, hypocomplimentemia, and ANCA positivity (PR3 Ab positive). Biopsy of her palpable purpuric rash demonstrated vascular immune deposition pattern consistent with leukocytoclastic vasculitis. Renal biopsy revealed focal and crescentic glomerulonephritis with immune complex deposition. CT abdomen noted mesenteric lymphadenopathy with fluid surrounding the thoracic aortic graft. Surface echocardiogram showed bioprosthetic AV replacement with diffuse cusp thickening without stenosis or regurgitation. At this point, a multidisciplinary team offered a broad differential diagnosis of inflammatory vasculitis versus culture-negative endocarditis with plan for further testing. Follow-up whole-body and cardiac PET scan identified FDG-avid abnormalities involving the aortic graft and AV with hypermetabolic soft tissue thickening surrounding the aortic root. Transesophageal echocardiogram confirmed AV thickening with a 1 cm mobile echodensity. Additional serologic testing identified positive Bartonella henselae IgG (1:8192) and IgM (>1:20) titers. The final diagnosis was B. henselae prosthetic AV endocarditis and ascending aortic graft infection. She underwent repeat AV and ascending aortic graft replacement, with graft material positive for B. henselae PCR and was treated with a course of doxycycline and rifampin. B. henselae is a fastidious gram-negative bacterium that can cause culture negative endocarditis but is very rarely associated with aortic graft infection. This case highlights (1) a rare example of B. henselae aortic graft infection, (2) the difficulty in differentiating B. henselae endocarditis from inflammatory vasculitis, and (3) the importance of engaging multidisciplinary teams to solve difficult diagnostic cases.

Chylothorax after chimeric antigen receptor T cell therapy for relapsed and refractory diffuse large B-cell lymphoma: A case report.

Anti-CD19-targeted chimeric antigen receptor (CAR) T cell therapy is effective in treating relapsed/refractory diffuse large B-cell lymphoma (DLBCL). This therapy is associated with several side effects that can be life-threatening such as cytokine release syndrome (CRS). However, chylothorax associated with CRS after CAR-T therapy has not been reported. A 23-year-old male diagnosed with DLBCL relapsing after autologous peripheral blood stem cell transplantation was treated with anti-CD19-targeted CAR-T cell therapy. After CAR-T cell transfusion, he developed grade 3 CRS includes fever, dyspnea, tachycardia and hypotension. The symptoms of CRS persisted and chest plain film revealed bilateral pleural effusion. Chylothorax was confirmed by the pleural effusion analysis that triglyceride level was 1061 mg/dL. Bacterial and fungal culture of pleural fluid reported no pathogen was detected. Cytological examination of pleural effusion revealed no malignant cells. The chylothorax resolved after treatment with intravenous administration of tocilizumab. On 30-day follow-up, the patient was in stable clinical condition with complete remission of DLBCL on whole-body positron emission tomography scan. We reported a rare case of CAR-T associated chylothorax in a patient with relapsed and refractory DLBCL. Grade 3 CRS with high interleukin-6 level was presented in our patient. The symptoms of CRS were improved with tocilizumab treatment and the chylothorax resolved later on. It is suggested that high interleukin-6 releases might induce chyle leakage resulting from activations of endothelium and coagulation. Our finding highlights the occurrence of chylothorax during the course of CAR-T cell therapy and the importance of proper monitoring and prompt management of this life-threatening side effect.

SAT245 Hips Don’t Lie: A Case Of Peri-Prosthetic Pseudotumor Leading To Hypercalcemia After Total Hip Replacement.

Abstract Disclosure: F. Sotomayor: None. H. Whitlatch: None. Background: Peri-prosthetic pseudotumors are well described, yet rare complications of total hip replacement. They can present as destructive or granulomatous lesions. We present the first documented case of 1,25 vitamin D-mediated severe hypercalcemia caused by a periprosthetic granuloma. Case: A 62-year-old man with a history of osteoporosis, ankylosing spondylitis presented with hypercalcemia (calcium 12.2 mg/dL) on routine laboratory testing. He had a history of bilateral cement hip arthroplasty in 1981 followed by multiple bilateral revisions - three revisions of left hip arthroplasty, one revision of right hip arthropasty. Biochemical evaluation included PTH 5 pg/mL (8 - 54 pg/mL), PTHrP 2.7 pmol/L (0.0 - 2.3 pmol/L), vitamin D-25 59 ng/mL (20-80 ng/mL), a negative Quantiferon TB Gold, and normal serum protein electrophoresis. 1,25 Vitamin D was elevated at 280.5 pg/mL (19.9-79.3 pg/mL). During investigation of 1,25 vitamin D-mediated hypercalcemia, he received a dose of zoledronic acid with transient improvement in hypercalcemia. ACE was negative and CT chest and abdomen was without evidence of granulomatous disease. A whole-body PET scan showed increased metabolic activity surrounding the right femoral and acetabular components with a broad zone of osteolysis in the proximal femur and increased metabolic activity surrounding the left greater trochanter. These findings were concerning for inflammatory granuloma formation. He was prescribed prednisone 30 mg daily with rapid normalization of serum calcium. Prednisone was gradually tapered to 10 mg daily with maintenance of normocalcemia. Discussion: Pseudotumors are an uncommon complication of total hip arthroplasty. These are described as non-infectious and non-neoplastic adverse soft tissue reactions to implants. They manifest as destructive or granulomatous periprosthetic lesion. They cause osteolysis, erosions, pathological fractures, and dislocations. Their formation is due to foreign body reaction to polyethylene, methylmethacrylate, cement or metal adjacent to the joint implant. Associated inflammation leads to macrophage activation, prostaglandin release, and osteolysis. Histologically, they are characterized by the presence of macrophages, extensive coagulation necrosis, lymphocytes, eosinophilic infiltration and granulomatous reaction. While non-malignant, they can cause extensive bony destruction and may require complex revision surgery. To date, this is the first reported case of hypercalcemia due to excess 1,25 vitamin D caused by a periprosthetic granuloma. Conclusion: Hypercalcemia is a well-described complication of granulomatous diseases, including sarcoidosis, mycobacterium infection, and lymphoma. In patients with a history of arthroplasty, we recommend adding peri-prosthetic pseudotumors to the differential diagnosis of 1,25 vitamin D mediated hypercalcemia. Presentation: Saturday, June 17, 2023

Dosimetric Plan Evaluation of Biology Guided Radiotherapy Using [18F]-DCFPyL PSMA Radiotracer in Patients with Prostate Cancer

The X1 system represents a cutting-edge solution in radiotherapy delivery, with its capability to perform Biology Guided Radiotherapy (BgRT). The system utilizes real-time positron emission tomography (PET) signal as biological fiducials to provide tracked dose delivery and is initially available for use with [18F]-Fluorodeoxyglucose (FDG). The aim of this research study is to assess the quality of BgRT treatment plans for prostate cancer using patients' PSMA PET images obtained on the X1 system. Sixteen patients with at least one PET-avid tumor identified on their whole-body diagnostic PSMA PET scan were selected. These patients were scanned on X1 following their diagnostic scan without additional radiotracer administration. Based on the X1 PET images, a BgRT plan was created for each patient, with the prescription dose determined by the location of treatment sites. The planning objectives of organs-at-risk (OARs) were established in accordance with the 2018 Timmerman guidelines. Target coverage objective was the dose covering 95% (D95%) of the planning target volume (PTV) to be higher than 100%. The following parameters were analyzed: PTV D95%, the minimal dose (Dmin) of gross tumor volume (GTV), plan maximum dose (Dmax), conformity index (CI), gradient index (GI), and maximum point dose (D0.03cc) to the nearest OARs. The X1 BgRT planning system also generated dose volume histogram (DVH) bounds, which model variations in BgRT delivery. The low boundary of GTV Dmin, representing the minimum GTV dose in the worst-case scenario, was recorded. BgRT plans were created for all patients, except for one where the target signal was indistinguishable from the bladder. The prescription dose was 2700 cGy or 3000 cGy in 3 fractions for lymph node lesions, 2400 cGy to 3000 cGy in 3 fractions for bone metastasis, and 4500 cGy in 5 fractions for lesions in prostate. All plans met the dose constraints for OARs as per the Timmerman guidelines. The Dmax of all plans was 129.9% ± 6.9% (mean ± standard deviation). The PTV D95% and GTV Dmin were 101.7% ± 1.0% and 111.0% ± 7.6%, respectively. The low boundary of GTV Dmin was 95.9% ± 5.8%. The CI and GI were 1.22 ± 0.11 and 9.40 ± 2.12, respectively. The D0.03cc to nearest OARs was 84.6% ± 25.4%. The estimated treatment time was 699 ± 228 seconds. This study is a pioneering effort to evaluate the quality of BgRT plans for prostate cancer patients using the [18F]-DCFPyL PSMA radiotracer. Our results showed that all BgRT plans met the planning objectives defined in the Timmerman protocol. BgRT with [18F]-DCFPyL represents a promising treatment modality for patients with prostate cancer. Further research is needed to validate this approach, including a comprehensive assessment of the dosimetric and tracking accuracy through physical measurements.

SDPS-08 OSSEOUS METASTASES IN H3G34-MUTANT DIFFUSE HEMISPHERIC GLIOMAS

Abstract Subset of patients with H3G34 gliomas may present with extra-CNS metastasis further complicating both diagnosis and treatment. We describe a case of a 19-year-old female presenting initially with focal motor seizure in right leg along with leg pain. MRI of the leg showed an ill-defined right distal femur expansile osteolytic lesion with central fluid signal, thick rim enhancement, endosteal scalloping, cortical invasion, and smooth enhancing periosteal reaction/soft tissue extension associated with surrounding enhancing marrow signal abnormality worrisome for lesion extension. Contrast brain MRI exhibited multiple frontal and partial lobe T2 FLAIR hyperintense lesions. The largest lesion demonstrated contrast enhancement, internal foci of restricted diffusion, and a focus of intratumoral hemorrhage. A whole-body PET/CT showed intensely FDG-avid lytic lesion in the right distal femur, with FDG activity along the biopsy tract. Hypermetabolic lytic metastases to the right femoral head and mid-sacral body were also observed. A craniotomy with brain lesion biopsy two months later indicated preliminary histopathology of malignant small round blue cell neoplasm. A biopsy from the distal right femur was non-diagnostic of malignancy but a sacral bone biopsy reported malignant small blue cell neoplasm, consistent with involvement by the patient's known cranial neoplasm. Final pathological diagnosis including molecular diagnostics was consistent with WHO grade 4 IDH-wildtype H3G34 mutant diffuse hemispheric glioma with osseous metastases. Patient was treated with chemoradiotherapy with temozolomide (TMZ). Following the sixth cycle of TMZ, MRI brain imaging was stable. Apart from holocephalic headaches, the patient had no significant medication side effects and was seizure-free. A second whole-body PET scan showed improvement and interval decrease in FDG uptake of the sacrum and right femoral head. Given the stress that patients with H3G34 can experience and the poor prognosis, it is imperative to expand our knowledge and ascertain accurate screening and diagnostic methodologies.

Biodistribution and Internal Dosimetry of 68 Ga-DOTA-IBA PET Imaging for Patients With Bone Metastases.

We have developed a new pharmaceutical, ibandronic acid (IBA), and preliminarily demonstrated that it is an efficient bisphosphonate for the diagnosis and treatment of bone metastases. This study aims to examine the biodistribution and internal dosimetry of the diagnostic 68 Ga-DOTA-IBA in patients. 68 Ga-DOTA-IBA was intravenously injected based on 1.81-2.57 MBq/Kg into 8 patients with bone metastases. Each patient underwent 4 sequential static whole-body PET scans at 0.1, 0.45, 0.8, and 1.8 hours after injection. The acquisition time for each scan was 20 minutes with 10 bed positions. Image registrations and volume of interest delineation were first performed on Hermes, whereas percentage injected activity (%IA), absorbed dose, and effective dose were measured for source organs, using OLINDA/EXM v2.0. Dosimetrics for the bladder was based on a bladder voiding model. No adverse effects were observed on all patients. After the injection, 68 Ga-DOTA-IBA rapidly accumulated in bone metastases and cleared from nonbone tissues, as indicated by visual analysis and %IA measured on the sequential scans. High activity uptake was presented in the expected target organs, that is, bone, red marrow, and the drug-excretion organs such as kidneys and bladder. The mean total body effective dose is 0.022 ± 0.002 mSv/MBq. 68 Ga-DOTA-IBA has high bone affinity and is promising in the diagnosis of bone metastases. Dosimetric results show that the absorbed doses for critical organs and total body are within the safety limit and with high bone retention. It also has the potential to be used in 177 Lu-therapy as a theranostic pair.