Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome.

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery.

Long-term survival outcomes of salvage [225Ac]Ac-PSMA-617 targeted alpha therapy in patients with PSMA-expressing end-stage metastatic castration-resistant prostate cancer: a real-world study.

PURPOSE: Despite the existence of various treatment options, the prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) remains unfavorable. One potential therapeutic approach is the use of [225Ac]Ac-PSMA-617, a targeted alpha therapy (TAT) that administers alpha-particle radiation specifically to prostate cancer cells expressing PSMA. In this study, we report the long-term survival outcomes of this novel therapy in a series of patients with mCRPC who have exhausted all standard treatment options. METHODS: The study enrolled patients with mCRPC who had shown resistance to standard lines of therapies, including next-generation anti-androgen therapies and taxane-based chemotherapies. These eligible patients received treatment with [225Ac]Ac-PSMA-617 at 100-150 kBq/kg doses administered every 8 weeks. The primary objective of the study was to assess overall survival (OS), while secondary objectives included evaluating radiological progression-free survival (rPFS), monitoring serum prostate-specific antigen (PSA) levels as a measure of biochemical response, and assessing adverse events using the CTCAE v5.0 grading system. RESULTS: Among the 63 initially enrolled patients, a total of 56 patients who had completed at least two cycles of [225Ac]Ac-PSMA-617 were included in this study. The mean age was 67 years (range, 39-87) and patients received a total of 204 cycles of [225Ac]Ac-PSMA-617 TAT. 91% of patients exhibited any PSA decline, with 67.8% experiencing a decline of 50% or more. The median follow-up was of 22 months (range: 6-59 months). Imaging-based disease progression was observed in 68% of patients, and 66% of patients succumbed to the disease. The median OS was 15 months (95% CI: 10-19). In univariate analysis, factors such as lack of >50% PSA decline (P=0.031), Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher (P=0.048), and radiological progression (rPD) (P<0.001) were found to be predictors of poor OS. However, in multivariate analysis, only rPD emerged as an independent prognostic factor with a hazard ratio (HR) of 8.264 (95% CI: 1.429-16.497, P=0.004). The estimated median rPFS was 9 months (95% CI: 7-15). Moreover, patients who demonstrated any PSA decline had a median rPFS of 10 months compared to only 3 months in patients without any PSA decline (multivariate HR: 6.749; 95% CI: 1.949-23.370; P=0.002). Fatigue was one of the most common treatment-emergent adverse events, with grades 1/2 occurring in 70% of patients and grades 3 or higher in 3.5% of patients. This fatigue was transient and resolved before the next treatment cycle. Additionally, approximately one-third of patients experienced xerostomia (grades 1/2: 32.1%). CONCLUSION: [225Ac]Ac-PSMA-617 targeted alpha therapy, was found to be well-tolerated with acceptable adverse events and effective in the treatment of patients with end-stage mCRPC.

Impact of Fluoro-Choline PET/CT in Reduction in Failed Parathyroid Localization in Primary Hyperparathyroidism.

INTRODUCTION: Accurate localization of the pathological parathyroid gland is a prerequisite for minimally invasive surgical management of hyperparathyroidism (HPT). Poor imaging or discordance in odd situations like ectopic adenomas, parathyroid hyperplasia, syndromic HPT results in localization dilemma thus causing failed parathyroidectomy. We studied the impact of Fluoro-Choline (FCH) PET/CT imaging in reduction in localization failure of parathyroid adenoma. MATERIALS AND METHODS: We did a retrospective observational study (2018-2021) of HPT among which 97 patients underwent focused parathyroidectomy (FP). All patients had undergone ultrasound imaging and 99mTc-sestaMIBI scan with early SPECT/CT (MIBI). When this preliminary imaging was doubtful or negative or multiple lesions were expected, FCH PET/CT was performed. We compared the localization accuracy of MIBI scan and FCH PET/CT with surgical outcomes as reference standard. RESULTS: MIBI scan showed overall lesion detection rate (LDR) of 88.65% in localization of pathological parathyroid gland in 97 patients. The addition of FCH PET/CT improved the overall lesion detection to 97.9%. The overall possible localization failure was reduced from 11.34 to 2.06% with the addition of FCH PET/CT (p < 0.05). Out of 97 patients of FP, 87 patients showed features of parathyroid adenoma. Single hyperplastic gland was seen in 7 patients, lipoadenoma was seen in 1 patient and 1 patient had features suggestive of parathyroiditis on histopathology. FCH PET/CT was a useful adjunct and showed significant reduction in localization failure of parathyroid adenoma.

Imaging characteristics of phosphaturic mesenchymal tumors.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome associated with phosphaturic mesenchymal tumors (PMTs). Localization of the causative tumor in these cases is an arduous task since the culprit lesions are usually small, slow-growing, and can be located almost anywhere from head to toe. PURPOSE: To describe the morphological characteristics of histologically proven PMTs on various radiological modalities. MATERIAL AND METHODS: After institutional ethical approval, this retrospective study analyzed 20 cases with a histopathological evidence of PMT. Various imaging characteristics of the tumors on available computed tomography (CT) and magnetic resonance imaging (MRI) scans were evaluated. Descriptive statistical analyses were conducted. RESULTS: The tumors were located in diverse locations: lower extremities (n = 10); head and neck (n = 5); vertebral column (n = 3); pelvis (n = 1); and upper extremities (n = 1). Bone lesions seen on CT had variable morphology: sclerotic (n = 3/8, 37.5%); lytic (n = 3/8, 37.5%), and both lytic and sclerotic (n = 2/8, 25%) with presence of narrow zone of transition in all cases (n = 8/8) and amorphous internal matrix calcifications in 25% of cases (n = 2/8). Of the tumors, 68.4% (n = 13/19) were hypointense on T1 and all of them showed hyperintense signal on T2-weighted and STIR images (n = 19/19) and contrast enhancement (n = 16/16). Of the tumors, 66.7% (n = 6/9) showed restricted diffusion. DOTANOC PET/CT showed tumor uptake in all cases (n = 8/8). CONCLUSION: PMTs may have variable and non-specific tumor appearances on various imaging modalities. However, in an appropriate clinical scenario and a background of suggestive biochemical work-up, the radiologist should keep a high index of suspicion.

Ga-68 PSMA PET/CT in recurrent high-grade gliomas: evaluating PSMA expression in vivo.

PURPOSE: We planned this prospective study to evaluate PSMA expression in recurrent high-grade gliomas (rHGG), including anaplastic astrocytoma and glioblastoma using Glu-NH-CO-NH-Lys-(Ahx)-[Ga-68 (HBED-CC)]- (Ga-68 PSMA) positron emission tomography (PET), with its theranostic potential in mind. METHODS: This was a prospective study enrolling patients with clinical and MRI evidence of rHGG on follow-up. Three treated cases of HGG with RN on MRI were also included as negative controls. Abnormal tracer accumulation in the brain parenchyma, more than the contralateral hemisphere was interpreted as positive study. For semiquantitative analysis, a 3D spherical region of interest (ROI) was drawn around the site of the abnormal Ga-68 PSMA uptake, and the ratio of SUVmax of tumor (T) to SUVmax of the contralateral corresponding area (TBR) was calculated. Each patients' PSMA brain PET was fused to the corresponding MRI and reviewed for concordance. RESULTS: Thirty patients were included in the study, a total of 49 lesions were detected on MRI, and fused PET/MR images showed increased Ga-68 PSMA uptake in all these lesions. Multifocal lesions were better appreciated on fused PET-MR images, and concordance between MRI and PET was 100 % for patient and lesion-wise detection. Recurrent glioma lesions showed SUVmax and SUVmean values (median and IQR) 6.0 (4.4-8.2) and 3.3 (2.8-3.7), respectively. Lesions labeled as radiation necrosis on MRI did not show tracer accumulation. CONCLUSION: Ga-68 PSMA has potential utility for evaluating recurrence in HGG and its potential for theranostics would encourage its use in the evaluation of these patients.

Undiagnosed Fever in a TB Contact Patient: An Unusual Cause.

IgG4-Related Disease(IgG4-RD) is a rare disease that can present with myriad clinical features. We report a tuberculosis contact case who presented with fever and constitutional complaints with imaging evidence of paravertebral and retroperitoneal soft tissue thickening. Further workup, including tissue biopsy ruled out tuberculosis and revealed diagnosis to be IgG4-related disease. Patient was started on oral steroids, which led to symptomatic improvement. In a TB endemic country such as ours, for a patient presenting with pleural and/or peritoneal fibrosis, a differential diagnosis of IgG4-RD must be kept.

Bowel Excretion of Technetium-99mL, L-Ethylene Dicysteine Masquerading as a Dilated Ureter in a Case of Pelvi-Ureteric Junction Obstruction: Case Report and Review.

The treatment plan and the decision for surgery in a significant proportion of patients with pelvi-ureteric junction (PUJ) obstruction type of hydronephrosis are dependent on the findings of renal scintigraphy. We report a case of a 3.5-year-old girl with right-sided PUJ obstruction, wherein the tracer excretion into the cecum and ascending colon complicated the clinical picture thereby misleading the final diagnosis or treatment plan and blurring the distinction between hydronephrosis and hydroureteronephrosis. Additional investigations may be required in such cases to reach a conclusion. The authors considered reporting this case in view of the deep-rooted clinical implications toward making a correct diagnosis. Besides, the possible mechanisms to explain the presence of the tracer inside the bowel have been discussed.

Metabolic topography of autoimmune non-paraneoplastic encephalitis.

PURPOSE: F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is emerging to be a useful tool in supporting the diagnosis of AIE. In this study, we describe the metabolic patterns on F-18 FDG PET imaging in AIE. METHODS: Twenty-four antibody-positive patients (anti-NMDA-15, anti-VGKC/LGI1-6, and anti-GAD-3), 14 females and 10 males, with an age range of 2-83 years were included in this study. Each PET study was evaluated visually for the presence of hypometabolism or hypermetabolism and semiquantitatively using Cortex ID (GE) and Scenium (Siemens) by measuring regional Z-scores. These patterns were correlated with corresponding antibody positivity once available. RESULTS: Visually, a pattern of hypometabolism, hypermetabolism, or both in various spatial distributions was appreciated in all 24 patients. On quantitative analysis using scenium parietal and occipital lobes showed significant hypometabolism with median Z-score of -3.8 (R) and -3.7 (L) and -2.2 (R) and -2.5 (L) respectively. Two-thirds (16/24) showed significant hypermetabolism involving the basal ganglia with median Z-score of 2.4 (R) and 3.0 (L). Similarly on Cortex ID, the median Z-score for hypometabolism in parietal and occipital lobes was -2.2 (R) and -2.4 (L) and -2.6 (R) and -2.4 (L) respectively, while subcortical regions were not evaluated. MRI showed signal alterations in only 11 of these patients. CONCLUSION: There is heterogeneity in metabolic topography of AIE which is characterized by hypometabolism most commonly involving the parietal and occipital cortices and hypermetabolism most commonly involving the basal ganglia. Scenium analysis using regional Z-scores can complement visual evaluation for demonstration of these metabolic patterns on FDG PET.

177Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment.

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of a novel theranostic agent, 177Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer (mCRPC). METHODS: Thirty-one mCRPC patients with progressive disease despite second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic68Ga-PSMA-HBED-CCPET/CT, prior to inclusion for therapy. Included patients then underwent quarterly 177Lu-DKFZ-PSMA-617 therapy. Hematological, kidney function, liver function tests, and serum PSA levels were recorded before and after therapy at 2 weeks, 4 weeks, and 3 month intervals. Biochemical response was assessed with trend in serum PSA levels. Metabolic response was assessed by PERCIST 1 criteria. Clinical response was assessed by visual analogue score (VASmax) analgesic score (AS), Karanofsky performance status (KPS), and ttoxicity and response criteria of the Eastern Cooperative Oncology Group (ECOG) criteria. RESULTS: The mean age of patients was 65.93 ± 9.77 years (range: 38-81 years). The mean activity administered in the 31 patients was 5069 ± 1845 MBq ranging from one to four cycles. There was a decline in the mean serum PSA levels from the baseline (baseline: 275 ng/mL, post 1st cycle therapy: 141.75 ng/mL). Based on biochemical response criteria 2/31, 20/31, 3/31, and 6/31 had complete response (CR), partial response(PR), stable disease (SD), and progressive disease (PD), respectively. Metabolic response revealed 2/6 patients with CR, and the remaining 3/6 patients with PR and 1/6 patients with SD. The mean VASmax score decreased from 7.5 to 3. The mean analgesic score decreased from 2.5 to 1.8 after therapy. The mean KPS score improved from 50.32 to 65.42 after therapies. The mean ECOG performance status improved from 2.54 to 1.78 after therapy. Two patients experienced grade I and grade II hemoglobin toxicity each. None of the patients experienced nephrotoxicity or hepatotoxicity. CONCLUSION: 177Lu-DKFZ-PSMA-617 radionuclide therapy is a safe and effective approach in the treatment of mCRPC patients.

Production of the PET bone agent (18)F-fluoride ion, simultaneously with (18)F-FDG by a single run of the medical cyclotron with minimal radiation exposure- a novel technique.

Our aim was to establish an easy and convenient procedure for the preparation of fluorine-18-sodium fluoride ((18)F-NaF) for bone positron emission tomography (PET) during routine (18)F-FDG production using the Explora FDG4 radiochemistry module (EFRM) by single run of Cyclotron with negligible radiation exposure. We compared three techniques for (18)F-NaF production during routine PET radiochemistry at our setup. In one method we used synthesis module and in other two methods we did not. In the first and third method, F-18 was directly extracted from the V-vial and in the second method, (18)F-NaF was extracted by post processing from the EFRM. In the first method, F-18 was extracted directly from V-vial manually by opening the V-vial cap. In the second method, Explora FDG-4 Module was used. First, F-18 was transferred from the V-vial. Then, after post processing in EFRM, pure F-18 was obtained in the product vial. In the third method, pure F-18 was obtained in the product vial with the help of a mechanical robotic arm. The above were followed by routine quality control of (18)F-NaF produced by each method. Results of quality control of the (18)F-NaF obtained by all three methods satisfied all parameters prescribed by the United States Pharmacopeia (USP) and the British Pharmacopeia (BP) including biological, physical and chemical specifications. The radiochemical purity was 98.5±1.5% with Rf 0.006. The level of Kryptofix-222 (K222) in (18)F-NaF was within the prescribed limit. Mean pH of (18)F-NaF was 6.0±1.5. The exposure rate around the hot cell was negligible. In conclusion, from the results it was obvious that by our method number three (18)F-NaF was directly obtained from the V-vial using mechanical robotic arms. This method was the most appropriate with minimized radiation exposure to the handling Radiochemist and was also saving time as compared to the other two methods.

Pulmonary Mucoepidermoid Carcinoma Mimicking Carcinoid Lung on 18 F-FDG and 68 Ga-DOTANOC PET/CT.

ABSTRACT: Pulmonary mucoepidermoid carcinoma (PMEC) is a rare pulmonary neoplasm. Although 18 F-FDG PET/CT has been shown to present with increased metabolic activity in PMEC, literature does not report increased somatostatin receptor expression in these tumors. We present the case of a 15-year-old boy where PMEC mimicked a typical carcinoid of the lung on DOTANOC PET/CT by showing significant uptake on 68 Ga-DOTANOC.

68 Ga-DOTANOC PET/CT in 2 Siblings With Von Hippel-Lindau Disease.

ABSTRACT: Von Hippel-Lindau disease is a rare multisystem disorder that shows autosomal dominant inheritance. It is a cancer syndrome that is characterized by the development of a variety of benign and malignant tumors-CNS hemangioblastomas, retinal angiomas, endolymphatic sac tumors, renal cysts and tumors, pancreatic cysts and tumors, adrenal pheochromocytomas, and epididymal cystadenomas. Here we present the 68 Ga-labeled DOTANOC scans of 2 siblings who show an interesting spectrum of findings consistent with Von Hippel-Lindau disease.

Role of FDG PET/CT in definitive and presumed autoimmune encephalitis.

OBJECTIVE: F-18 Fluorodeoxyglucose PET/CT (FDG-PET) is emerging as a useful imaging adjunct to MRI in the initial diagnostic evaluation of autoimmune encephalitis (AIE)-though presently it is not included in the diagnostic criteria. MATERIALS AND METHODS: In this prospective study we enrolled a total of 52 patients with clinically diagnosed and treated AIE. MRI evaluation was done in each case along with CSF and EEG where feasible. FDG-PET was done for all and images were interpreted visually and using SPM. RESULTS: The mean age group of patients included was 38.5 ± 22.6 years with 31 females and 21 males. 23 antibody-positive cases underwent PET, the most common antibody detected was anti-NMDAR type followed by anti-LGI 1. Most common metabolic pattern in NMDARE was hypermetabolism in basal ganglia and hypometabolism in parieto-occipital cortices and ovarian teratoma was detected in two of these patients on whole-body PET. A metabolic pattern consistent with AIE was demonstrated in 22/29 (75.8%) antibody-negative patients with hypermetabolism in basal ganglia and mesial temporal cortices. The overall sensitivity of FDG PET was 86% (45/52). MRI abnormalities were detected in 22/52 (42%) cases, 10/23 antibody positive and 12/29 antibody negative cases. PET was positive in 23/30 (76%) MRI negative cases. CONCLUSION: Sensitivity of FDG PET for supporting a diagnosis of AIE was higher compared to MRI in both antibody-positive (definitive) and antibody-negative (presumed) AIE. Specific metabolic patterns can be demonstrated on FDG PET in AIE, prompting an early diagnosis so that timely treatment can be instituted.

Odd Sites of Parathyroid Adenomas: 18F-fluorocholine PET/CT Pointing to the Right Place.

Primary hyperparathyroidism is mostly caused by parathyroid adenoma(s) which are generally localized using routine imaging modalities such as neck ultrasonography and 99mTc-SestaMIBI scintigraphy. However, these can miss ectopic parathyroid adenomas due to their limited sensitivities. These ectopic lesions can later lead to failure of surgical excision and necessitate the need for a re-exploration. 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) can help in the localization of these ectopic adenomas due to its superior detection rates and spatial resolution. Herein, we report a case of ectopic parathyroid adenomas that were localized on FCH PET/CT.

Radioiodine Therapy in Pediatric Differentiated Thyroid Cancer: Dosimetry, Clinical Care, and Future Challenges.

ABSTRACT: Thyroid cancer is very rare in children. 131 I therapy after thyroidectomy is established in pediatric differentiated thyroid cancer (DTC). Pediatric DTC guideline is silent on the optimum amount of 131 I that could be safely and effectively administered to children who are more radiosensitive. Like adult DTC, children are also given 131 I therapy empirically based either on age or body weight. Pediatric DTC guideline recommends that patient-specific dosimetry is important in children. Still, due to the low incidence rate and the practical difficulties of dosimetry, it has neither been established nor adopted in routine practice. This review article aims to discuss current approaches of 131 I therapy in children and young adult patients with DTC and dosimetric data obtained by several investigators. Efforts are required to simplify dosimetric procedures and precise results, especially in determining lesion size. We prefer 3-dimensional dosimetry over planar dosimetry, where lesion size could be measured accurately. 124 I PET/CT-based dosimetry is expected to give accurate dosimetric results. The most challenging aspect is that no randomized controlled trials are available to compare the empiric 131 I therapy results versus dosimetry-based treatment outcomes in children and young adults. Suppose dosimetry-based 131 I therapy could be shown to have better outcomes, namely, successful ablation rate, better disease-free survival, and lesser treatment-emergent adverse events than empirical 131 I treatment. In that case, one can argue in favor of the former. Unfortunately, no convincing study is currently available. Thus, there is a need for a randomized control trial to settle this issue.

Malignancy-Associated Sarcoid-Like Reaction in a Case of Triple-Negative Breast Cancer on F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

We describe the case of a 54-year-old woman with triple-negative breast cancer whose baseline F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showed hypermetabolic left breast primary, ipsilateral axillary lymphadenopathy, lung nodules, and mediastinal lymph nodes. Histopathological examination of tissue from mediastinal lymph nodes confirmed a diagnosis of sarcoid-like reaction. Chemotherapy may induce or cause a flare-up of malignancy-associated sarcoid-like reaction. However, in our patient's post-chemotherapy F-18 FDG PET/CT, there was reduction in size and uptake of the mediastinal lymph nodes along with partial response shown by the other lesions. We aim to describe this rare course of malignancy-associated sarcoid-like reaction and highlight the role of F-18 FDG PET-CT in such cases.

Extensive Metastatic Vascular Calcification in a Patient with Chronic Renal Failure and Tubercular Osteomyelitis as Seen on F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

A 48-year-old male with known tubercular osteomyelitis of the left elbow and chronic renal failure presented with PTH independent hypercalcemia and underwent F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) to look for any underlying malignancy that might be causing his hypercalcemia. The PET/CT did not reveal any malignancy, but extensive metastatic calcification of small- and medium-sized arteries was noted throughout the body with relative sparing of large vessels. Alkaline tissue such as lungs, gastric mucosa, and kidneys that are usually involved in metastatic calcification were also spared. The underlying pathology for this kind of metastatic calcification was most likely chronic granulomatous disease, which was tubercular osteomyelitis in this patient. We present the PET/CT scan images of this unusual case of metastatic vascular calcification.

Lincoln Sign in a Case of Primary Hyperparathyroidism on 18 F-Fluorocholine PET/CT.

ABSTRACT: Lincoln sign or black beard sign is one of the signs that have been classically described on bone scintigraphy in monostotic Paget disease, when mandible is involved. Extensive involvement of the mandible causes increased radiotracer uptake from one mandibular condyle to the other, resembling a black beard. We present the case of a 14-year-old girl with primary hyperparathyroidism who underwent an 18 F-fluorocholine PE/CT to locate the parathyroid adenoma. MIP image of the PET/CT incidentally showed black beard sign due to increased radiotracer uptake in the mandible.