Increased Tracer Uptake Research Articles

6581 Case of Conversion from Hashimoto’s Thyroiditis to Graves’ Disease: An Unusual Sequence

Abstract Disclosure: A. Atri: None. C. Anastasopoulou: None. Introduction: The two most common autoimmune thyroid diseases are Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). HT is a destructive thyroiditis, via autoantibodies most commonly against the thyroid peroxidase enzyme (anti-TPO), while GD results in hyperthyroidism, due to TSH-receptor stimulating antibodies (TSAb) and Thyroid Stimulating Immunoglobulin (TSI). Case Report: A 23-year-old male presented to the clinic with complaints of weight gain, dry skin and excessive hair loss. His physical examination was non-contributory and laboratory evaluation revealed a TSH of 130 uIU/ml (ref: 0.45-4.5), free T4 (fT4) 0.4 ng/dl (ref: 0.82-1.77), and positive anti-TPO antibodies, for which he was started on levothyroxine (LT4) supplementation for newly diagnosed HT. Over the first five months on treatment, his TSH and T4 progressively improved to 31.8 uIU/ml and 1.48 ng/dl, respectively. Six months later, his TSH rapidly decreased to 0.01 uIU/ml, with an fT4 elevation to 2.45 ng/dl, alongside developing hyperthyroid symptoms like weight loss, insomnia and palpitations. Due to persistently positive anti-TPO antibody titers, his hyperthyroidism was considered iatrogenic, and LT4 dose was gradually reduced, but eventually required to be discontinued. A thyroid ultrasound depicted generalized increase in vascularity, consistent with active thyroiditis. He continued to have a significantly suppressed TSH <0.005 uIU/ml and elevated fT4, off all medications, and was also found to have multiple positive antibody titers [TSI of 1.02 IU/L (ref: < 0.55), thyroglobulin antibody of 351 IU/ml (< 0.9) and anti-TPO Ab >600 IU/ml (ref< 34)]. He was then diagnosed with new GD, and thyroid suppression therapy with 10mg/day of methimazole was initiated, to which he rapidly responded, with a TSH of 0.059 uIU/ml and reduced fT4 of 1.37 ng/dl. His diagnosis of GD was confirmed via an I-123 thyroid uptake scan which revealed a homogenous increased tracer uptake of 57% at 24 hours (ref 15-35%), following which he received definitive therapy for GD, with radio-active iodine (RAI) ablation with 20.6 mCi of I-131. Discussion: As HT and GD have a common autoimmunity-based pathophysiology, conversions between the two clinical states have been described, though HT to GD, as seen in our patient is much less common than the reverse conversion. Some described mechanisms include an antibody switch from thyrotropin receptor blocking to stimulating action, HT-induced thyrotroph destruction resulting in GD antibody formation, and treatment with LT4. Simultaneously elevated levels of both TSI and anti-TPO can occur, and therefore treatment and diagnosis should be based on thyroid function tests and clinical presentation. Patients with autoimmune thyroid disease require close monitoring, due to the potential risk of conversion from one clinical end of the spectrum to the other, and early recognition is important. Presentation: 6/1/2024

8257 Pancreatic Neuroendocrine Tumor Presenting As Carcinoid Syndrome

Abstract Disclosure: D. Phung: None. Introduction Pancreatic neuroendocrine tumors (NETs) are rare tumors that arise in neuroendocrine cells of the pancreas. These tumors secrete a wide array of hormones. Carcinoid syndrome is a result of well-differentiated neuroendocrine tumors that secrete biologically active amines and peptides that cause the clinical manifestation of flushing, diarrhea, cardiac involvement, and wheezing. Case Presentation A 57-year-old male presented to the clinic for symptoms of tachycardia, shortness of breath, dizziness, and sweating for the past year. He had past medical history of chronic kidney disease, history of previous cardiac arrest, history of previous myocardial infarction, congestive heart failure, hypertension and gastric reflux disease. No history of tobacco, alcohol, or drug consumption. No previous surgeries. Family history with heart disease and prostate cancer in his father. His symptoms began over the course of the past year. Initially began with shortness of breath, chest pain, weight gain which then developed into dizziness with standing, episodes of night time sweating. He had associated headaches that were occurring daily. Vomiting would occur intermittently three to four times weekly. He noted episodes of flushing with rash occurring in the upper chest and bilateral arms. Diarrhea and loose bowel movements would occur occasionally. On examination he had tachycardia with heart rate at 103 BPM. Lung fields clear throughout. Abdomen was soft, nontender, without masses palpated. On biochemical testing chromogranin A was highly elevated and remained elevated upon repeat testing. Initial imaging with CT abdomen and pelvis with contrast was negative. PET scanning confirmed and localized his NET, revealing increased tracer uptake and hypervascularity in the neck of pancreas as well as two regions in the right lower lobe of the liver. Following confirmation and localization of his tumor he was then referred for surgical evaluation and treatment. Discussion In our presented case, the patient presented with symptoms suggestive of carcinoid syndrome which was confirmed biochemically with elevated chromogranin A. Clinical suspicion remains critical in diagnosis of NETs. The patient presented with clinically suspicious carcinoid syndrome, but initial testing with CT scan was negative and required further PET-based tracing to uncover tumors. Our case highlights the importance of clinical examination and acumen in diagnosing neuroendocrine tumors. Presentation: 6/2/2024

8257 Pancreatic Neuroendocrine Tumor Presenting as Carcinoid Syndrome

Abstract Disclosure: D. Phung: None. Introduction Pancreatic neuroendocrine tumors (NETs) are rare tumors that arise in neuroendocrine cells of the pancreas. These tumors secrete a wide array of hormones. Carcinoid syndrome is a result of well-differentiated neuroendocrine tumors that secrete biologically active amines and peptides that cause the clinical manifestation of flushing, diarrhea, cardiac involvement, and wheezing. Case Presentation A 57-year-old male presented to the clinic for symptoms of tachycardia, shortness of breath, dizziness, and sweating for the past year. He had past medical history of chronic kidney disease, history of previous cardiac arrest, history of previous myocardial infarction, congestive heart failure, hypertension and gastric reflux disease. No history of tobacco, alcohol, or drug consumption. No previous surgeries. Family history with heart disease and prostate cancer in his father. His symptoms began over the course of the past year. Initially began with shortness of breath, chest pain, weight gain which then developed into dizziness with standing, episodes of night time sweating. He had associated headaches that were occurring daily. Vomiting would occur intermittently three to four times weekly. He noted episodes of flushing with rash occurring in the upper chest and bilateral arms. Diarrhea and loose bowel movements would occur occasionally. On examination he had tachycardia with heart rate at 103 BPM. Lung fields clear throughout. Abdomen was soft, nontender, without masses palpated. On biochemical testing chromogranin A was highly elevated and remained elevated upon repeat testing. Initial imaging with CT abdomen and pelvis with contrast was negative. PET scanning confirmed and localized his NET, revealing increased tracer uptake and hypervascularity in the neck of pancreas as well as two regions in the right lower lobe of the liver. Following confirmation and localization of his tumor he was then referred for surgical evaluation and treatment. Discussion In our presented case, the patient presented with symptoms suggestive of carcinoid syndrome which was confirmed biochemically with elevated chromogranin A. Clinical suspicion remains critical in diagnosis of NETs. The patient presented with clinically suspicious carcinoid syndrome, but initial testing with CT scan was negative and required further PET-based tracing to uncover tumors. Our case highlights the importance of clinical examination and acumen in diagnosing neuroendocrine tumors. Presentation: 6/2/2024

7576 A Rare and Atypical Presentation of Bladder Paraganglioma in a Patient on Long-Term Left Ventricular Assist Device

Abstract Disclosure: S.D. Leungsuwan: None. S.J. Lee: None. S.D. Lim: None. L. Loh: None. Background: Paragangliomas (PGLs) are rare neuroendocrine tumors arising from chromaffin cells. Capable of producing catecholamines, functional PGLs often cause a myriad of autonomic symptoms and complications, including cardiomyopathy. We report a case of bladder PGL in a patient on Left Ventricular Assist Device (LVAD). Clinical Case: A 64-year-old Chinese Female with a history of non-ischaemic cardiomyopathy on long-term continuous LVAD and Cardiac Resynchronisation Therapy Defibrillator (CRT-D) was admitted for recurrent low LVAD flow <2 Litres per minute and labile mean arterial pressure (MAP) 57-151mmHg. She has been on long-term Nebivolol, Entresto, Hydralazine, and Sildenafil without recent dose adjustment. Workup for acute illnesses was non-contributory. 24-hour urine metanephrine and normetanephrine (NM) were 939nmol/d [normal 400-1500nmol/d] and 33883nmol/d [normal 600-1900nmol/d] respectively. Plasma free metanephrine and NM were 0.37nmol/L [normal <0.33nmol/L] and >10.00nmol/L [normal <0.99nmol/L] accordingly. A review of previous ultrasonography and Computed Tomography (CT) imaging revealed a right adnexal mass indenting the bladder which the patient formerly declined further assessment; adrenal glands were normal. FDG-PET CT was done and showed an isolated focus of increased tracer uptake corresponding with the right pelvic mass. An impression of likely bladder PGL was made. A multidisciplinary team including Cardiology, Anaesthesiology, Interventional Radiology (IR), Urology, Gynaecology, and Endocrinology was convened; the patient was recommended surgical resection of the tumor. Preoperatively, she was started on phenoxybenzamine 10mg BD and advised judicious fluid and salt intake. Nebivolol was continued while hydralazine was stopped. This achieved targets of i) MAP 70-80mmHg, ii) approximately 10mmHg MAP postural fluctuation, iii) sitting and standing heart rates 60-70 beats-per-minute (BPM) and 70-80BPM, and iv) no more than 1 PVC every 5 minutes. Two weeks later, she underwent IR-guided angioembolisation and tumor resection uneventfully. Intraoperatively, the patient had haemodynamic fluctuations requiring dynamic administrations of phentolamine, norepinephrine, epinephrine, vasopressin, glyceryl trinitrate, and sodium nitroprusside. Histopathology was consistent with PGL with intact SDH-A and SDH-B expression. Postoperatively, phenoxybenzamine was discontinued and no recurrent LVAD low flow was noted. Subsequent plans for repeat plasma metanephrines and genetic studies were made. Discussion: This case is the first to report an atypical presentation of PGL with LVAD low flow and labile blood pressure. The significant elevations of urine NM (17.8x upper normal limit) and plasma NM (>10.1x upper normal limit) also underline the concept of fold-elevations and post-test probability of PGL. Presentation: 6/3/2024

Diffuse Uptake of 68Ga-Pentixafor in the Breasts During the Ovulatory Phase in a Patient With SAPHO Syndrome.

We report a case of a woman with SAPHO syndrome who exhibited increased tracer uptake in the sternal angle on a 99mTc-MDP bone scan. This patient was enrolled in a 68Ga-pentixafor PET/CT trial for inflammatory diseases. The PET/CT showed no abnormal tracer uptake in the sternal angle. Unexpectedly, diffuse uptake of 68Ga-pentixafor was observed in both breasts, which might be due to hormonal stimulation because the woman underwent the 68Ga-pentixafor PET/CT scan during the ovulatory phase.

Prostate-Specific Membrane Antigen-Positron Emission Tomography-Guided Radiomics and Machine Learning in Prostate Carcinoma.

Positron emission tomography (PET) using radiolabeled prostate-specific membrane antigen targeting PET-imaging agents has been increasingly used over the past decade for imaging and directing prostate carcinoma treatment. Here, we summarize the available literature data on radiomics and machine learning using these imaging agents in prostate carcinoma. Gleason scores derived from biopsy and after resection are discordant in a large number of prostate carcinoma patients. Available studies suggest that radiomics and machine learning applied to PSMA-radioligand avid primary prostate carcinoma might be better performing than biopsy-based Gleason-scoring and could serve as an alternative for non-invasive GS characterization. Furthermore, it may allow for the prediction of biochemical recurrence with a net benefit for clinical utilization. Machine learning based on PET/CT radiomics features was also shown to be able to differentiate benign from malignant increased tracer uptake on PSMA-targeting radioligand PET/CT examinations, thus paving the way for a fully automated image reading in nuclear medicine. As for prediction to treatment outcome following 177Lu-PSMA therapy and overall survival, a limited number of studies have reported promising results on radiomics and machine learning applied to PSMA-targeting radioligand PET/CT images for this purpose. Its added value to clinical parameters warrants further exploration in larger datasets of patients.

Association of Free-to-Total PSA Ratio and 18F-DCFPyL Prostate-Specific Membrane Antigen PET/CT Findings in Patients with Biochemical Recurrence After Radical Prostatectomy: A Prospective Single-Center Study.

In Canada and across the globe, access to PSMA PET/CT is limited and expensive. For patients with biochemical recurrence (BCR) after treatment for prostate cancer, novel strategies are needed to better stratify patients who may or may not benefit from a PSMA PET scan. The role of the free-to-total prostate-specific antigen (PSA) ratio (FPSAR) in posttreatment prostate cancer, specifically in the PSMA PET/CT era, remains unknown. Our aim in this study was to determine the association of FPSAR in patients referred for 18F-DCFPyL PSMA PET/CT in the BCR setting and assess the correlation between FPSAR and 18F-DCFPyL PSMA PET/CT positivity (local recurrence or distant metastases). Methods: This prospective study included 137 patients who were referred for 18F-DCFPyL PSMA PET/CT and had BCR with a total PSA of less than 1 ng/mL after radical prostatectomy (RP) (including adjuvant or salvage radiotherapy). Blood samples were collected on the day of 18F-DCFPyL PSMA PET/CT. FPSAR was categorized as less than 0.10 or as 0.10 or more. A positive 18F-DCFPyL PSMA PET/CT scan was defined by a PROMISE classification lesion score of 2 or 3, irrespective of the site of increased tracer uptake (e.g., prostate, pelvic nodes, bone, or viscera). Results: Overall, 137 blood samples of patients with BCR after RP were analyzed to calculate FPSAR. The median age at 18F-DCFPyL PSMA PET/CT was 68.6 y (interquartile range, 63.0-72.4 y), and the median PSA at 18F-DCFPyL PSMA PET/CT was 0.3 ng/mL (interquartile range, 0.3-0.6 ng/mL). Eighty-six patients (62.8%) had an FPSAR of less than 0.10, whereas 51 patients (37.2%) had an FPSAR of 0.10 or more. An FPSAR of 0.10 or more was identified as an independent predictor of a positive 18F-DCFPyL PSMA PET/CT scan, with an odds ratio of 6.99 (95% CI, 2.96-16.51; P < 0.001). Conclusion: An FPSAR of 0.10 or more after RP independently correlated with increased odds of a positive 18F-DCFPyL PSMA PET/CT scan among BCR post-RP patients. These findings may offer an inexpensive method by which to triage access to 18F-DCFPyL PSMA PET/CT in jurisdictions where availability is not replete.

Uptake of 68Ga-DOTA-FAPI-04 in a Case of Gynecomastia.

Herein, we report a case of a man with malignant melanoma exhibiting thickened right breast with increased tracer uptake on 68Ga-DOTA-FAPI-04 PET/CT. Subsequent ultrasound confirmed there was no sign of malignancy and consistent with benign gynecomastia.

Ex vivo optical coherence tomography combined with near infrared targeted fluorescence: towards in-vivo esophageal cancer detection.

Early detection of (pre)malignant esophageal lesions is critical to improve esophageal cancer morbidity and mortality rates. In patients with advanced esophageal adenocarcinoma (EAC) who undergo neoadjuvant chemoradiation therapy, the efficacy of therapy could be optimized and unnecessary surgery prevented by the reliable assessment of residual tumors after therapy. Optical coherence tomography (OCT) provides structural images at a (sub)-cellular level and has the potential to visualize morphological changes in tissue. However, OCT lacks molecular imaging contrast, a feature that enables the study of biological processes at a cellular level and can enhance esophageal cancer diagnostic accuracy. We combined OCT with near-infrared fluorescence molecular imaging using fluorescently labelled antibodies (immuno-OCT). The main goal of this proof of principle study is to investigate the feasibility of immuno-OCT for esophageal cancer imaging. We aim to assess whether the sensitivity of our immuno-OCT device is sufficient to detect the tracer uptake using an imaging dose (∼100 times smaller than a dose with therapeutic effects) of a targeted fluorescent agent. The feasibility of immuno-OCT was demonstrated ex-vivo on dysplastic lesions resected from Barrett's patients and on esophageal specimens resected from patients with advanced EAC, who were respectively topically and intravenously administrated with the tracer bevacizumab-800CW. The detection sensitivity of our system (0.3 nM) is sufficient to detect increased tracer uptake with micrometer resolution using an imaging dose of labelled antibodies. Moreover, the absence of layered structures that are typical of normal esophageal tissue observed in OCT images of dysplastic/malignant esophageal lesions may further aid their detection. Based on our preliminary results, immuno-OCT could improve the detection of dysplastic esophageal lesions.

Incidence of exclusive extrapelvic skeletal metastasis in prostate carcinoma on bone scintigraphy.

Bone is one of the common sites of metastasis from prostate carcinoma. Bone scintigraphy (BS) is one of the most sensitive imaging modalities currently used for bone metastatic work-up. Skeletal metastasis in prostate carcinoma commonly involves pelvic bones but rarely involves extrapelvic-extraspinal sites. To retrospectively analyze the BS data to determine the pattern of skeletal metastases in the prostate carcinoma. This retrospective observational study involves patients with biopsy-proven prostate carcinoma referred for BS for staging assessment. Patients with abnormal BS were evaluated for the pattern of skeletal involvement and data were presented in descriptive format in the form of percentages. A total of 150 patients with biopsy-proven prostate cancer who were referred for staging were included in the study. Thirteen of 150 patients (8.67%) had no abnormal uptake on planar images, ruling out metastatic disease. Twenty-four patients (16%) had heterogeneous uptake in the spine with distribution characteristic of degenerative disease and no scan pattern of metastatic disease. Thirty patients (20%) had multifocal uptake involving both pelvic and extra pelvic bones on planar images typical for skeletal metastasis and were considered metastatic. Eighty-three out of 150 patients (55.3%) had increased tracer uptake, which was indeterminate, thus, single photon emission computed tomography-computed tomography (SPECT-CT) was acquired, which showed 51 with metastatic disease, 31 benign lesions, and one indeterminate finding. Seven of 150 patients had exclusive pelvic bone uptake, which was found to be metastatic in 4/7 patients in SPECT-CT. Fifty six out of 150 patients showed exclusive extrapelvic tracer uptake, of which only 3 had vertebral metastatic disease. None of the patients with increased uptake exclusively in the extrapelvic-extraspinal location was metastatic. The incidence of exclusive extrapelvic skeletal metastatic disease in prostate carcinoma is 2% (excluding one patient with indeterminate findings). Further, none of the patients in the current study had exclusive extrapelvic-extraspinal metastasis. Thus, exclusive extrapelvic-extraspinal focal abnormality on planar BS carries a very low probability of metastatic disease and hence, further imaging or SPECT-CT can be safely avoided in such cases.

Dual-Tracer Positron Emission Tomography/Computed Tomography with [18F]FDG and [18F]fluorocholine in a Patient with Metastatic Parathyroid Carcinoma.

Here, we describe the case of a 43-year-old male patient with a metastatic parathyroid carcinoma who underwent dual-tracer whole-body positron emission tomography/computed tomography (PET/CT) with [18F]fluorocholine and fluorodeoxyglucose ([18F]FDG) for staging. [18F]FDG PET/CT detected multiple cervical and mediastinal lymph nodal lesions with increased tracer uptake, whereas [18F]fluorocholine PET/CT detected increased tracer uptake on cervical and mediastinal lymph nodal lesions and bone and lung lesions with a better evaluation of metastatic spread. Due to these imaging findings, the patient underwent systemic treatment with chemotherapy. This case demonstrates the added value of dual-tracer PET/CT in this rare metastatic tumor.

Assessment of tissue response in vivo: PET-CT imaging of titanium and biodegradable magnesium implants

To study in vivo the bioactivity of biodegradable magnesium implants and other possible biomaterials, we are proposing a previously unexplored application of PET-CT imaging, using available tracers to follow soft tissue and bone remodelling and immune response in the presence of orthopaedic implants. Female Wistar rats received either implants (Ti6Al7Nb titanium or WE43 magnesium) or corresponding transcortical sham defects into the diaphyseal area of the femurs. Inflammatory response was followed with [18F]FDG and osteogenesis with [18F]NaF, over the period of 1.5 months after surgery. An additional pilot study with [68Ga]NODAGA-RGD tracer specific to αvβ3 integrin expression was performed to follow the angiogenesis for one month.[18F]FDG tracer uptake peaked on day 3 before declining in all groups, with Mg and Ti groups exhibiting overall higher uptake compared to sham. This suggests increased cellular activity and tissue response in the presence of Mg during the initial weeks, with Ti showing a subsequent increase in tracer uptake on day 45, indicating a foreign body reaction. [18F]NaF uptake demonstrated the superior osteogenic potential of Mg compared to Ti, with peak uptake on day 7 for all groups. [68Ga]NODAGA-RGD pilot study revealed differences in tracer uptake trends between groups, particularly the prolonged expression of αvβ3 integrin in the presence of implants.Based on the observed differences in the uptake trends of radiotracers depending on implant material, we suggest that PET-CT is a suitable modality for long-term in vivo assessment of orthopaedic biomaterial biocompatibility and underlying tissue reactions. Statement of significanceThe study explores the novel use of positron emission tomography for the assessment of the influence that biomaterials have on the surrounding tissues. Previous related studies have mostly focused on material-related effects such as implant-associated infections or to follow the osseointegration in prosthetics, but the use of PET to evaluate the materials has not been reported before. The approach tests the feasibility of using repeated PET-CT imaging to follow the tissue response over time, potentially improving the methodology for adopting new biomaterials for clinical use.

Potential Efficacy of 68 Ga-Trivehexin PET/CT and Immunohistochemical Validation of αvβ6 Integrin Expression in Patients With Head and Neck Squamous Cell Carcinoma and Pancreatic Ductal Adenocarcinoma.

αvβ6 integrin is exclusively expressed in epithelial cells and is upregulated in many carcinomas, such as pancreatic ductal adenocarcinomas (PDACs) and head and neck squamous cell carcinomas (H&NSCCs). Trivehexin is a recently synthesized trimerized αvβ6 integrin selective nonapeptide, which can be labeled with a positron emitter like 68 Ga. This is a pilot study to assess the potential role of 68 Ga-Trivehexin PET/CT in patients with H&NSCC and PDAC and their correlation with αvβ6 integrin expression by the tumor tissue on immunohistochemistry (IHC). Thirty-two patients with suspected H&NSCC (n = 20) or PDAC (n = 12) underwent whole-body 68 Ga-Trivehexin PET/CT and 18 F-FDG PET/CT scans on 2 separate days. All 32 patients underwent biopsy from the tumor site for histopathological diagnosis and IHC for αvβ6 integrin expression. The degree of αvβ6 integrin expression on IHC was scored using the immunoreactive score and modified 4-point immunoreactive score classification. The 68 Ga-Trivehexin PET images demonstrated increased tracer uptake (mean SUV max 5.9 ± 3.3) in the primary and metastatic lesions with good lesion delineation in 8 out of the 9 cases of PDACs. However, FDG PET showed increased tracer uptake in 7 cases (6.2 ± 2.6). Among various cases of H&NSCC, increased uptakes of 68 Ga-Trivehexin (6.6 ± 4.5) and 18 F-FDG (12.7 ± 6.7) were seen in 17 out of the 18 patients. The 2 cases of inflammatory changes with suspected disease recurrence showed increased tracer uptake in 18 F-FDG PET (7.98 ± 3.1) and no significant uptake in 68 Ga-Trivehexin PET (2.2 ± 0.34).IHC showed higher expression of αvβ6 integrins in lesions with higher uptake of 68 Ga-Trivehexin. A higher sensitivity, specificity, and accuracy of 68 Ga-Trivehexin PET over 18 F-FDG PET was seen for detection of primary and metastatic lesions. 68 Ga-Trivehexin is a promising noninvasive molecular imaging agent for tumors expressing αvβ6 integrin, especially in cases where 18 F-FDG PET/CT scan may be suboptimal due to its low uptake, or due to its nonspecific uptake around tumor sites.

The Dark Side of Activated Phosphoinositide 3-Kinase-δ Syndrome 2: A Story Rewritten through FDG-PET.

Background: Activated phosphoinositide 3-kinase-δ syndrome 2 (APDS2) is characterized by lymphoproliferation and increased risk of malignancy. FDG-PET/CT may represent a helpful diagnostic tool for differentiating these clinical features and correctly diagnosing inborn errors of immunity (IEI). Case report: We present the case of a female patient diagnosed with Hodgkin's lymphoma at 19 years of age, although atypical imaging aspects emerged: baseline FDG-PET/CT revealed several hot lymph nodes with a symmetrical distribution, and increased tracer uptake in spleen, axial, and appendicular bone marrow. Imaging repeated after chemotherapy and autologous stem cell transplantation showed persistent increased FDG uptake at multiple supradiaphragmatic nodes and in bone marrow. After the diagnosis of APDS2 and rapamycin treatment, FDG-PET/CT confirmed complete metabolic normalization of all sites. Conclusions: In the IEI scenario, FDG-PET/CT plays an effective role in differentiating malignant proliferation and immune dysregulation phenotypes. Atypical patterns at FDG-PET/CT should be interpreted as a red flag for the need of an early immunological evaluation.

Neuroimaging-guided diagnosis of possible FTLD-FUS pathology: a case report

BackgroundThis case report presents a patient with progressive memory loss and choreiform movements.Case presentationNeuropsychological tests indicated multi-domain amnestic mild cognitive impairment (aMCI), and neurological examination revealed asymmetrical involuntary hyperkinetic movements. Imaging studies showed severe left-sided atrophy and hypometabolism in the left frontal and temporoparietal cortex. [18F]Flortaucipir PET exhibited moderately increased tracer uptake in hypometabolic areas. The diagnosis initially considered Alzheimer’s disease (AD), frontotemporal degeneration (FTD), and corticobasal degeneration (CBD), cerebral hemiatrophy syndrome, but imaging and cerebrospinal fluid analysis excluded AD and suggested fused-in-sarcoma-associated FTD (FTLD-FUS), a subtype of the behavioural variant of FTD.ConclusionsOur case highlights that despite the lack of specific FUS biomarkers the combination of clinical features and neuroimaging biomarkers can guide choosing the most likely differential diagnosis in a complex neurological case. Imaging in particular allowed an accurate measure of the topography and severity of neurodegeneration and the exclusion of AD-related pathology.

Defining the imaging diagnostic criteria for adult chronic non-bacterial osteitis.

Osteitis of the sternocostoclavicular (SCC) region, referred to as sternocostoclavicular hyperostosis (SCCH), is the clinical expression of chronic non-bacterial osteitis (CNO) in adults with this rare chronic auto-inflammatory disorder of the axial skeleton. The diagnosis is based on distinctive computerized tomography (CT) features of sclerosis and hyperostosis of the SCC region, and local increases in osteoid formation visualized by high radiopharmacon uptake on skeletal scintigraphy but clear radiologic diagnostic criteria are lacking. In a cross-sectional study, CT scans and whole-body skeletal scintigraphy images obtained in 169 patients seen at the Center for Bone Quality of the Leiden University Medical Center between 2008 and 2018 with a suspected diagnosis of CNO of the SCC region were re-evaluated by 2 skeletal radiologists and 2 nuclear physicians. The diagnosis was confirmed in 118 (70%) predominantly female patients (n= 103, 89.2%); median age at first symptoms 45years (range 20-73). The diagnosis was excluded in the remaining 51 "non-CNO" patients. Increased radiopharmacon uptake at the SCC region was observed in 82% CNO patients, with the manubrium sterni having the highest predictive ability to discriminate on both imaging modalities. The prevalence of sclerosis of the clavicles, manubrium and first ribs was significantly higher in CNO patients (P< 0.001). Hyperostosis was not observed in non-CNO patients. 46 CNO versus only 2 non-CNO patients had costoclavicular ligament calcification. Our findings identify CT scan features of sclerosis and hyperostosis of manubrium sterni, medial end of clavicles and first ribs, and calcification of costoclavicular ligaments, associated with increased tracer uptake on skeletal scintigraphy at the SCC region, specifically manubrium sterni, as well-defined imaging diagnostic criteria for adult CNO. Pitfalls encountered in the diagnosis of CNO are highlighted. These defined imaging diagnostic criteria for adult CNO should facilitate the diagnosis of this rare auto-inflammatory bone disease across the spectrum of its early to late stages.

Concomitant thyroiditis and orchitis induced by immune checkpoint inhibitors detected on [18F]FDG PET/CT

BackgroundThe clinical management of malignant melanoma (MM) has undergone a significant revolution with the implementation of immune checkpoint inhibitors (ICIs). While these therapeutic agents stimulate the host immune system against cancer, they may also lead to immune-related adverse events (IrAEs). Positron emission computed tomography (PET/CT) with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) has proven successful in detecting IrAEs in cancer patients undergoing ICI. In our case, we report a rare occurrence of ICIs-induced concomitant thyroiditis and orchitis detected on [18F]FDG PET/CT.Case presentationWe present a case involving a 61-year-old man referred to our hospital due to MM. Following surgical excision and sentinel lymph node mapping, he underwent an initial [18F]FDG PET/CT, which yielded negative results. However, a follow-up PET/CT after 9 months revealed metastases in the lungs and lymph nodes. Subsequently, he initiated an ICI-based therapeutic regimen. After 3 months, he reported progressively worsening fatigue and the onset of testicular pain. A testicular ultrasound showed heterogeneous echotexture in both testicles with mildly increased vascularity. A subsequent PET/CT demonstrated complete regression of previously described pathological lesions in the lungs and metastatic lymph nodes. However, diffusely increased tracer uptake was observed in both the thyroid gland and testicles, findings absent in the pre-ICI examination. These were interpreted as IrAEs and promptly treated with corticosteroids, resulting in complete resolution of symptoms.Conclusions[18F]FDG PET/CT plays a crucial role in staging and monitoring treatment response in cancer patients. When assessing subjects undergoing ICI-based therapies, particular emphasis should be given to detecting unusual IrAEs, as exemplified in our case.

High Diagnostic Accuracy of Thyroid-Stimulating Hormone (TSH) Receptor Antibodies in Distinguishing Graves' Disease and Subacute Thyrotoxicosis in the Indian Population.

Thyrotoxicosis is a common clinical condition encountered in endocrine practice. Graves' disease and subacute thyroiditis are the two common causes of thyrotoxicosis and often have overlapping clinical and biochemical features. 99mTc thyroid scintigraphy is the most commonly used confirmatory test to differentiate the two conditions but is not available in the majority of the second-tier cities of India. However, obtaining thyroid stimulating hormone (TSH) receptor antibodies (TSHrAb), another accurate test to differentiate the two conditions, in second-tier cities by outsourcing to labs in major cities is a feasible option nowadays. However, the data on the performance of TSHrAb to differentiate the two conditions in Indian patients is limited. Hence, we have evaluated the diagnostic accuracy of TSHrAb in the Indian population to differentiate Graves' disease and subacute thyroiditis. This prospective studywas conducted on 115 consecutive newly diagnosed thyrotoxicosis patients presenting to the Department of Endocrinology at a tertiary health care centre in India. Clinical parameters like throat pain, duration of symptoms, and grade of goitre were noted. Measurement of total tri-iodothyronine (TT3), total thyroxine (TT4), TSH, TSHrAb, and 99mTc thyroid scintigraphy were performed in all participants. All participants were followed up at least for six months after the recruitment. Increased tracer uptake (>4%) and/or increased thyroid to parotid trace uptake ratio (>2.5) were used to diagnose Graves' disease. Eighty-one and 34 patients were diagnosed with Graves' disease and subacute thyroiditis, respectively. TT3/TT4 ratio had low diagnostic accuracy (area under the curve (AUC): 0.6, best cut-off: 15.6, sensitivity: 53.1%, specificity: 79.4%). TSHrAb had the best AUC (0.9) to distinguish Graves' disease from subacute thyroiditis (cut-off: 2.0 IU/L, sensitivity: 97.5%, specificity: 100%). In contrast, the kit manufacturer's reference range (1.75 IU/L) was slightly more sensitive (98.8%), but less specific (94%). The TT3/TT4 ratio is not a good test to differentiate Graves' disease and subacute thyroiditis. TSHrAb is accurate in distinguishing Graves' disease from subacute thyroiditis and a level of 2.0 may be a more accurate cut-off to differentiate the two conditions in the Indian population.

2-[18F]-FDG PET/CT Semiquantitative and Radiomics Predictive Parameters of Richter's Transformation in CLL Patients.

Background and Objectives: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in developed countries, which can evolve into aggressive lymphoma variants, a process called Richter transformation (RT). The aim of this retrospective study was to analyze the role of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]-FDG PET/CT) and its semiquantitative and radiomics features in detecting RT and evaluate the impact on overall survival (OS). Materials and Methods: One hundred and thirty-seven patients with histologically proven CLL were retrospectively recruited. PET/CT images were qualitatively and semiquantitatively examined by estimating the main metabolic parameters (the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), lesion-to-blood-pool SUV ratio (L-BP SUV R), lesion-to-liver SUV ratio (L-L SUV R), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and radiomics first- and second- order variables of the lesion with highest uptake. The role of these parameters in predicting RT and OS was analyzed. Results: One hundred and thirty (95%) PET/CT scans were positive, showing an increased tracer uptake at the site of disease, whereas the remaining 7 (5%) scans were negative. SUVbw, SUVlbm, SUVbsa, L-L SUV ratio, and L-BP SUV ratio were significantly higher in the RT group (p < 0.001 in all cases). Radiomics first- and second-order features were not significantly associated with RT. After a median follow-up of 44 months, 56 patients died; OS was significantly shorter in patients with RT than patients without RT (28 vs. 34 months; p = 0.002). Binet-stage, RT, and L-BP SUV R were shown to be independent prognostic features. Conclusions: Semiquantitative PET/CT parameters such as SUVbw, SUVlbm, SUVbsa, L-L SUV ratio and L-BP SUV ratio may be useful in discriminating patients with a high risk of developing RT, whereas Binet-stage, RT, and L-BP SUV R are also significant in predicting OS.

Tumor Burden of Iodine-Avid Bone Metastatic Thyroid Cancer Identified via 18F-Sodium Fluoride PET/CT Imaging.

Patients with differentiated thyroid cancer (DTC) are referred to radioactive 131I (RAI) therapy and post-therapy 131I whole-body scintigraphy (WBS) to identify local and/or remote metastases. Positron emission tomography (PET)/computed tomography (CT) imaging with 18F-fluoro-D-glucose (FDG) or 18F-sodium fluoride (NaF) may also be used with these patients for the evaluation of bone metastases. We compared the role of 18F-NaF PET/CT and 18F-FDG-PET/CT in patients with DTC and documented bone metastases at post-therapy WBS. Ten consecutive DTC patients with iodine avid bone metastasis at post-therapy WBS referred to 18F-NaF PET/CT and 18F-FDG PET/CT were studied. The findings of the three imaging procedures were compared for abnormal detection rates and concordance. At post-therapy 131I WBS, all patients had skeletal involvement with a total of 21 bone iodine avid lesions. At 18F-FDG PET/TC, 19 bone lesions demonstrated increased tracer uptake and CT pathological alterations, while 2 lesions did not show any pathological finding. At 18F-NaF PET/CT, the 19 bone lesions detected at 18F-FDG PET/TC also demonstrated abnormal tracer uptake, and the other 2 bone iodine avid foci did not show any pathological finding. In patients with DTC, 18F-NaF PET/CT did not obtain more information on the metastatic skeletal involvement than post-therapy 131I WBS and 18F-FDG PET/CT.