Incidental Detection of Parathyroid Adenoma on 18F-PSMA PET/CT.

ABSTRACT: A 70-year-old man, diagnosed with prostate cancer, was referred to the Department of Nuclear Medicine for tumor staging with prostate-specific membrane antigen (PSMA) PET/CT. High PSMA uptake was observed in the prostate without PSMA-avid lymph nodes or distant metastases. Coincidentally, a PSMA-avid nodule was observed dorsal to the right thyroid lobe. A complementary 4-dimensional CT showed a round nodule of 18 mm with quick contrast enhancement well demarcated from its surroundings. Blood tests revealed elevated serum calcium and parathyroid hormone consistent with primary hyperparathyroidism. Subsequently, parathyroidectomy was performed, and histopathological examination of the nodule confirmed a parathyroid adenoma.

FDG-Avid Granulomatous Lymphocytic Interstitial Lung Disease With Common Variable Immunodeficiency.

ABSTRACT: A 26-year-old woman with known common variable immunodeficiency was referred for FDG PET/CT because of interstitial pulmonary abnormalities and enlarged mediastinal and hilar lymph nodes. FDG PET showed a combination of ground-glass abnormalities and pulmonary nodules, both displaying increased FDG uptake. In addition, multiple FDG-avid axillary, mediastinal, hilar, and inguinal lymph nodes were found. The abnormalities were diagnosed as granulomatous-lymphocytic interstitial lung disease. Cytology of mediastinal lymph nodes yielded only benign disease, without further specification, whereas histology of an excised axillary lymph node showed reactive changes, but no malignancy.

Radiosynoviorthesis: almost seventy years of experience but still somewhat fameless.

Radiosynoviorthesis (RSO) or radiation synovectomy has been practiced for more than half a century, but in many parts of the world, it is still relatively unknown and not used to its full potential in the standard care for chronic, persistent or recurrent synovitis. The working mechanism of RSO is simple yet elegant. Radiopharmaceutical particles are, after injection in the affected synovial joint, gobbled up by phagocytizing subsynovial inflammatory cells. As a consequence, the synovium will be irradiated locally resulting in synovial cell necrosis and inhibition of cell proliferation, which eventually leads to a decrease in the inflammatory response in the joint cavity. In this review RSO is once again brought to the attention and common indications for RSO are discussed. Also, appropriate activities of the administrated radiopharmaceuticals and coadministrated glucocorticoids are provided. Furthermore, a detailed database-assisted chronological overview of published literature of RSO in inflammatory and non-inflammatory diseases, like rheumatoid arthritis, psoriatic arthritis, osteoarthritis and osteochrondomatosis, hemophilic hemarthrosis and pigmented villonodular synovitis (PVNS) is provided. Based upon the published literature an indication of level of evidence of RSO is discussed. There is evidence that RSO is effective in persistent synovitis in patients with a variety of causes for synovitis, although the effectiveness seems to decrease over time. In these patients, RSO may not be used to its full potential in many parts of the world. Results in of RSO in hemophilia patients with hemarthrosis are favourable, however the evidence for the effectiveness of RSO in these patients is less firm and mainly based on case series. The evidence for the efficacy of RSO as adjuvant therapy in PVNS is, at best, of very low quality.

Athletic Osteitis Pubis Detected on 18 F-FDG PET/CT.

ABSTRACT: A 37-year-old male personal trainer presented with debilitating groin pains, fever, and night sweats. Enlarged inguinal lymph nodes were noticed during physical examination, and blood tests showed elevated erythrocyte sedimentation rate and C-reactive protein. 18 F-FDG PET/CT excluded lymphoma and other malignancy but showed intense FDG uptake at the pubic symphysis and cortical erosions of the pubic bones on CT. The patient was diagnosed with osteitis pubis, an inflammatory condition of the pubic symphysis commonly seen in athletes. Treatment with anti-inflammatory drugs was initiated. Within several weeks, pain decreased, and inflammatory markers normalized.

Multi-task Deep Learning of Myocardial Blood Flow and Cardiovascular Risk Traits from PET Myocardial Perfusion Imaging.

BACKGROUND: Advanced cardiac imaging with positron emission tomography (PET) is a powerful tool for the evaluation of known or suspected cardiovascular disease. Deep learning (DL) offers the possibility to abstract highly complex patterns to optimize classification and prediction tasks. METHODS AND RESULTS: We utilized DL models with a multi-task learning approach to identify an impaired myocardial flow reserve (MFR <2.0 ml/g/min) as well as to classify cardiovascular risk traits (factors), namely sex, diabetes, arterial hypertension, dyslipidemia and smoking at the individual-patient level from PET myocardial perfusion polar maps using transfer learning. Performance was assessed on a hold-out test set through the area under receiver operating curve (AUC). DL achieved the highest AUC of 0.94 [0.87-0.98] in classifying an impaired MFR in reserve perfusion polar maps. Fine-tuned DL for the classification of cardiovascular risk factors yielded the highest performance in the identification of sex from stress polar maps (AUC = 0.81 [0.73, 0.88]). Identification of smoking achieved an AUC = 0.71 [0.58, 0.85] from the analysis of rest polar maps. The identification of dyslipidemia and arterial hypertension showed poor performance and was not statistically significant. CONCLUSION: Multi-task DL for the evaluation of quantitative PET myocardial perfusion polar maps is able to identify an impaired MFR as well as cardiovascular risk traits such as sex, smoking and possibly diabetes at the individual-patient level.

Focal PSMA-Positive Pleural Lesion in a Patient With Stage II Prostate Carcinoma.

ABSTRACT: A 70-year-old man with histopathologically proven prostate carcinoma (Gleason, 5 + 5; prostate-specific antigen level, 6.2 µg/mL) was referred for an 18F-PSMA-1007 PET/CT scan. The scan revealed bilateral PSMA uptake in the prostate, representing the primary tumor, but no evidence of PSMA-positive lymph nodes. However, a left-sided ventral pleural thickening showed focal PSMA uptake. Lesion biopsy showed no signs of malignancy, and prostatectomy was performed. The 1-year follow-up CT thorax showed growth of approximately 20% of the pleural lesion. Subsequently, video-assisted thoracic surgery of the lesion was performed. Histopathology showed a solitary fibrous tumor, a rare mesenchymal tumor.

Matched-Pair Comparison of 18F-DCFPyL PET/CT and 18F-PSMA-1007 PET/CT in 240 Prostate Cancer Patients: Interreader Agreement and Lesion Detection Rate of Suspected Lesions.

Over 20 different prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals for both imaging and therapy have been synthesized. Although variability in biodistribution and affinity for binding to the PSMA receptor is known to exist between different PSMA-targeting radiopharmaceuticals, little is known about the clinical implications of this variability. Therefore, this study analyzed differences in interreader agreement and detection rate between 2 regularly used 18F-labeled PSMA receptor-targeting radiopharmaceuticals: 18F-DCFPyL and 18F-PSMA-1007. Methods: One hundred twenty consecutive patients scanned with 18F-PSMA-1007 were match-paired with 120 patients scanned with 18F-DCFPyL. All 240 PET/CT scans were reviewed by 2 readers and scored according to the criteria of the PSMA Reporting and Data System. Interreader agreement and the detection rate for suspected lesions were scored for different anatomic locations such as the prostate, prostatic fossa, lymph nodes, and bone. Results: Great equality was found between 18F-DCFPyL and 18F-PSMA-1007; however, some clinically relevant and statistically significant differences were observed. 18F-PSMA-1007 detected suspected prostatic or prostatic fossa lesions in a higher proportion of patients and especially in the subcohort scanned for biochemical recurrence. 18F-DCFPyL and 18F-PSMA-1007 showed an equal ability to detect suspected lymph nodes, although interreader agreement for 18F-DCFPyL was higher. 18F-DCFPyL showed fewer equivocal skeletal lesions and higher interreader agreement on skeletal lesions. Most of the equivocal lesions found with 18F-PSMA-1007 at least were determined to be of nonmetastatic origin. Conclusion: Clinically relevant differences, which may account for diagnostic dilemmas, were observed between 18F-DCFPyL and 18F-PSMA-1007. Those findings encourage further studies, as they may have consequences for selection of the proper PSMA-targeting radiopharmaceutical.

"Skull on Fire": Monostotic Paget Disease of the Skull Bone.

An 81-year-old woman was evaluated for a stroke. CT showed no intracranial abnormalities but diffuse patchy aspect of the neurocranium. An MRI and F-NA PET/CT were performed to differentiate between metastases, Paget disease, hyperostosis frontalis interna, and primary malignancy. MRI yielded no additional findings. F-NA PET/CT showed diffusely increased uptake in the skull and 4 spots with intense uptake. No other suspicious skeletal foci were seen elsewhere. Low-dose CT showed no sign of malignancy elsewhere. Image findings together with elevated serum alkaline phosphatase levels, slightly increased calcium levels, and normal phosphorus levels were interpreted as pathognomic for monostotic Paget.

Clinical verification of 18F-DCFPyL PET-detected lesions in patients with biochemically recurrent prostate cancer.

PURPOSE: Radiolabeled Prostate-Specific Membrane Antigen (PSMA) PET/CT is the current standard-of-care for lesion detection in patients with biochemically recurrent (BCR) prostate cancer (PCa). However, rigorous verification of detected lesions is not always performed in routine clinical practice. To aid future 18F-radiolabeled PSMA PET/CT interpretation, we aimed to identify clinical/imaging characteristics that increase the likelihood that a PSMA-avid lesion is malignant. MATERIALS AND METHODS: 262 patients with BCR, who underwent 18F-DCFPyL PSMA PET/CT, were retrospectively analyzed. The malignant nature of 18F-DCFPyL PET-detected lesions was verified through any of the following metrics: (1) positive histopathological examination; (2) additional positive imaging; (3) a ≥50% decrease in Prostate-Specific Antigen (PSA) following irradiation of the lesion(s). RESULTS: In 226/262 PET scans (86.3%) at least one lesion suspicious for recurrent PCa was detected ('positive scan'). In 84/226 positive scans (37.2%), at least one independent verification metric was available. PSMA PET-detected lesions were most often confirmed to be malignant (PCa) in the presence of a CT-substrate (96.5% vs. 55.6% without CT-substrate), with SUVpeak ≥3.5 (91.4% vs. 60.0% with SUVpeak<3.5), in patients with a PSA-level ≥2.0 ng/mL (83.7% vs. 65.7% in patients with PSA <2.0ng/mL) and in patients with >2 PET-positive lesions (94.1% vs. 64.2% in patients with 1-2 PET-positive lesions; p<0.001-0.03). CONCLUSIONS: In this study, the clinical verification of 18F-DCFPyL PET-positive lesions in patients with BCR was performed. Diagnostic certainty of PET-detected lesions increases in the presence of characteristic abnormalities on CT, when SUVpeak is ≥3.5, when PSA-levels exceed 2.0 ng/mL or in patients with more than two PET-positive lesions.

Dynamic 18F-fluorocholine PET/CT for parathyroid imaging in patients with primary hyperparathyroidism.

OBJECTIVE: In the past few years, F-fluorocholine PET/CT has been established as a promising imaging technique for preoperative localization of parathyroid adenomas, but the optimal time point to start PET/CT acquisition after tracer injection is yet unknown. The aim of the present study was to assess the optimal time frame to acquire the PET/CT images and to evaluate the ability of dynamic imaging to differentiate parathyroid adenomas from active lymph nodes, a common cause for false-positive scan results. PATIENTS AND METHODS: Patients with primary hyperparathyroidism who had undergone a dynamic F-fluorocholine PET/CT positive for parathyroid disease and who subsequently underwent successful parathyroidectomy were retrospectively included in this study. On the 20 minutes dynamic images, standardized uptake value measurements were acquired per 1 minute frame for the parathyroid adenoma, the thyroid gland, blood pool activity, and, if present, lymph node activity. RESULTS: A total of 101 patients were included in this study. Time-activity curves showed a decrease of activity in parathyroid and thyroid glands, with faster wash-out from the thyroid gland and on average a stable, lower activity in lymph nodes. Blood pool activity was particularly present in the first 2 minutes. Differentiation of a parathyroid adenoma from active lymph nodes was best before 5 minutes, but no definitive cutoff value could be determined. Differentiation of a parathyroid adenoma from the thyroid gland was best after 10 minutes. CONCLUSION: Dynamic imaging starting at the early time point of 2 minutes after injection of F-fluorocholine is useful for characterization of hyperfunctioning parathyroid glands.

Incidental Breast Carcinoma Detected With 13N-NH3 Cardiac PET Imaging.

A 78-year-old woman with chest pain and a history of pacemaker implantation for arrhythmia underwent myocardial perfusion imaging by means of N-NH3 cardiac PET/CT. N-NH3 cardiac PET showed no signs of ischemia or infarction. Incidentally, a nodule with increased N-NH3 activity was observed in the right breast. Histopathologic examination revealed invasive ductal carcinoma.

18F-DCFPyL Uptake in an Incidentally Detected Follicular Lymphoma by PET/CT Performed for Biochemically Recurrent Prostate Cancer.

A 75-year-old man, treated with curative intent for histopathologically proven prostate cancer (initial prostate-specific antigen, 27 ng/mL; Gleason 4 + 5 = 9) through external beam radiation therapy in 2010 in combination with 3 years of androgen deprivation therapy (leuprorelin), underwent F-DCFPyL PET/CT for biochemical recurrence with a prostate-specific antigen of 4.1 ng/mL in February 2019. Multiple pelvic and some para-aortic lymph nodes showed highly increased F-DCFPyL uptake, suspicious for metastases. Incidentally, a solid mesenteric mass and mesenteric lymph nodes with moderately increased F-DCFPyL uptake were found. Upon histopathological evaluation, this proved to be a low-grade follicular lymphoma.

Ventricular synchrony is not significantly determined by absolute myocardial perfusion in patients with chronic heart failure: A 13N-ammonia PET study.

BACKGROUND: It is thought that heart failure (HF) patients may benefit from the evaluation of mechanical (dys)synchrony, and an independent inverse relationship between myocardial perfusion and ventricular synchrony has been suggested. We explore the relationship between quantitative myocardial perfusion and synchrony parameters when accounting for the presence and extent of fixed perfusion defects in patients with chronic HF. METHODS: We studied 98 patients with chronic HF who underwent rest and stress Nitrogen-13 ammonia PET. Multivariate analyses of covariance were performed to determine relevant predictors of synchrony (measured as bandwidth, standard deviation, and entropy). RESULTS: In our population, there were 43 (44%) women and 55 men with a mean age of 71 ± 9.6 years. The SRS was the strongest independent predictor of mechanical synchrony variables (p < .01), among other considered predictors including: age, sex, body mass index, smoking, diabetes mellitus, dyslipidemia, hypertension, rest myocardial blood flow (MBF), and myocardial perfusion reserve (MPR). Results were similar when considering stress MBF instead of MPR. CONCLUSIONS: The existence and extent of fixed perfusion defects, but not the quantitative PET myocardial perfusion parameters (sMBF and MPR), constitute a significant independent predictor of ventricular mechanical synchrony in patients with chronic HF.

Parathyroid imaging with 18F-fluorocholine PET/CT as a first-line imaging modality in primary hyperparathyroidism: a retrospective cohort study.

BACKGROUND: 18F-fluorocholine (FCH) PET/CT is a promising technique for visualizing hyperfunctioning parathyroid glands in hyperparathyroidism. It is still under debate whether to use this technique as a first-line imaging modality or to use it when conventional techniques such as 99mTc-sestamibi scintigraphy or ultrasonography are inconclusive. This study evaluates FCH PET/CT as a first-line modality. METHODS: Patients with primary hyperparathyroidism, referred between June 2015 and December 2018 for FCH PET/CT as a first-line imaging method, were included in this study. Baseline characteristics, clinical data, scan results, and type of treatment were recorded. The rate of correct detection was calculated on a per patient-based and a per lesion-based analysis. The reference standard comprised histopathological results, intraoperative response to parathyroidectomy, and clinical follow-up. RESULTS: Two hundred and seventy-one patients were included, of which 139 patients underwent parathyroidectomy, 48 were treated with calcimimetics, and 84 patients received further follow-up without active treatment. In the surgically treated group, a single adenoma was suspected in 127 scans, double adenoma in three scans, and one scan showed evidence of three hyperfunctioning glands. In eight scans, no lesions were visualized. A total of 154 parathyroid glands were surgically removed. The rate of correct detection was calculated at 96% and 90%, on a per patient-based and per lesion-based analysis, respectively. CONCLUSION: This retrospective study in a large cohort shows high detection rates of FCH PET/CT in primary hyperparathyroidism, which is in accordance to literature. The use of FCH PET/CT as a first-line imaging modality in preoperative planning of parathyroid surgery may therefore be a suitable choice.

18F-DCFPyL PET/CT in a Single Large Metastasis With Prostate-Specific Antigen Level of 856 ng/mL.

Literature shows that prostate-specific membrane antigen (PSMA) PET/CT may detect biochemical recurrence of prostate cancer at low prostate-specific antigen (PSA) levels, including detection of oligometastatic disease and hence direct metastasis-directed therapy. Although it is generally accepted that higher PSA values indicate higher disease burden, few data are available on the relation between PSA levels and number of detected metastases on PSMA PET/CT. This report demonstrates a patient with high PSA levels (856 ng/mL) at time of biochemical recurrence that showed only 1 metastasis on PSMA PET/CT. Combined androgen deprivation therapy and radiation therapy resulted in a complete biochemical response.

Effect of forced diuresis during 18F-DCFPyL PET/CT in patients with prostate cancer: activity in ureters, kidneys and bladder and occurrence of halo artefacts around kidneys and bladder.

Forced diuresis may improve readability of 2-(3-(1-carboxy-5-[(6-[F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid (F-DCFPyL) PET/computed tomography (CT) by reducing focal ureteral activity. A total of 40 patients received furosemide simultaneously with F-DCFPyL (cohort 1) and 40 patients received furosemide 85 min after F-DCFPyL administration (cohort 2). The frequency of occurrence of activity depositions in ureters and halo artefacts near the kidneys and bladder was measured, as well as intensity of F-DCFPyL uptake in kidneys and bladder. At 120 min after injection of F-DCFPyL, a significantly lower number of F-DCFPyL depositions in ureters was found in cohort 2. Moreover, F-DCFPyL uptake in kidneys and bladder was significantly lower in this cohort; however, the occurrence of halo artefacts was similar in both groups. Administration of furosemide may improve interpretation of F-DCFPyL PET/CT as it results in less activity depositions in ureters. However, the effect depends on the timing of furosemide administration in relation to F-DCFPyL administration and PET/CT acquisition time. Acquisition of PET-images 120 min after F-DCFPyL administration benefits from late furosemide administration (85 min after injection).

Dual-Time-Point 18F-Fluorocholine PET/CT in Parathyroid Imaging.

18F-fluorocholine (18F-FCH) PET/CT is a promising and increasingly used scan technique in the preoperative imaging of parathyroid adenoma. Several acquisition methods have been evaluated in the literature, but the optimal image acquisition time point after administration of the tracer is still under debate. Methods: Patients who had hyperparathyroidism, underwent dual-time-point 18F-FCH PET/CT (image acquisition, 5 min; 60 min after injection), and had histologically proven pathologic parathyroid glands were retrospectively included in the study. Early and late images were compared both visually and quantitatively. Results: Sixty-four patients were included, and a total of 71 parathyroid glands were surgically removed. Visually, there were no differences between early and late images of hyperfunctioning parathyroid glands in 44 patients (69%); in 13 patients (20%), visualization on early images was better; in 6 patients (9%), visualization of hyperfunctioning glands was best on late images; and in 1 patient (2%), the lesion was exclusively visualized on late images. For the total cohort, there was a significant decrease in 18F-FCH uptake in the glands on late versus early time points (P = 0.001), but there was a significant increase in the ratio of parathyroid uptake to thyroid uptake (P = 0.037). The group of patients with better visualization on early images showed a decrease over time in both parathyroid uptake and the ratio of parathyroid uptake to thyroid uptake, significant in comparison to those in both the group with better visualization at later time points and the group in which visualization was similar at both time points (P values of 0.000-0.018). There were no significant differences in 18F-FCH uptake and the ratio of parathyroid uptake to thyroid uptake between the latter 2 groups (P values of 0.200-0.709). Conclusion: In most patients (89%), hyperfunctioning parathyroid glands were adequately visualized on early imaging; however, in a subset of patients (11%), such glands were best visualized at later time points. Therefore, we recommend the acquisition of dual-time-point images in parathyroid imaging with 18F-FCH PET/CT or the creation of an opportunity to acquire additional late images after review of early images when findings are inconclusive.

Choline PET/CT in parathyroid imaging: a systematic review.

One of the most promising imaging techniques in primary hyperparathyroidism is PET/CT with choline-based tracers. To investigate the current evidence of these tracers in localizing parathyroid adenoma, a systematic review was performed. A comprehensive literature search was carried out and eligible studies were analyzed. Data were extracted, the level of evidence was scored, and performance data were pooled to calculate the weighted detection rate. Eleven articles were included in this study. The pooled detection rate was 97 and 94% on per patient-based and per lesion-based analysis, respectively. There was considerable heterogeneity between studies and the level of evidence was determined to be 3a-, following Oxford criteria. Choline PET/CT has shown favorable results in detection of hyperfunctioning parathyroid tissue and may replace conventional technetium-99m-sestamibi scintigraphy in preoperative planning of parathyroid surgery. However, the quality of current evidence is moderate, and additional high-quality studies are needed to confirm these numbers.

Effects of Fasting on 18F-DCFPyL Uptake in Prostate Cancer Lesions and Tissues with Known High Physiologic Uptake.

In the literature, a 4- to 6-h fast is recommended before a patient undergoes PET/CT with 2-(3-(1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid (18F-DCFPyL); however, a scientific underpinning for this recommendation is lacking. Therefore, we performed a study to determine the impact of fasting on 18F-DCFPyL uptake. Methods: The study included 50 patients who fasted at least 6 h before 18F-DCFPyL administration and 50 patients who did not. Activity (SUVmax) was measured in lesions characteristic of prostate cancer and in normal tissues known to express high physiologic uptake. Results: Uptake in suspected lesions did not differ between the cohorts. 18F-DCFPyL uptake in the submandibular gland, liver, and spleen was significantly higher in the fasting than the nonfasting cohort. Conclusion: Our data show that fasting does not significantly affect 18F-DCFPyL uptake in suspected malignant lesions but does result in significantly lower 18F-DCFPyL uptake in tissues with high physiologic uptake. The absolute differences in uptake were relatively small; therefore, the effects of fasting on the diagnostic performance can be considered negligible.

Accuracy of 18F-NaF PET/CT in bone metastasis detection and its effect on patient management in patients with breast carcinoma.

OBJECTIVE: Determination of the accuracy of sodium fluorine-18-fluoride (F-NaF) PET/computed tomography (CT) for the evaluation of bone metastases, and the impact on patient management in breast cancer patients. PATIENTS AND METHODS: Patients with breast cancer, referred for F-NaF PET/CT between February 2014 and June 2016, were included in a database. Baseline characteristics, clinical indication, definitive diagnosis according to follow-up data, as well as changes in patient management were recorded. Follow-up was performed during a period of at least 6 months using histopathologic, medical imaging, biochemical, and clinical data. RESULTS: A total of 118 patients were included in the study. Indications for F-NaF PET/CT included primary staging (12%), follow-up (31%), bone pain (52%), abnormal laboratory findings (5%), and evaluation of equivocal osseous lesions on other imaging modalities (3%). Bone metastases were found in 42%, whereas 53% of the scans were negative and 5% yielded equivocal results. Correlation with the reference standard yielded a sensitivity of 0.96, a specificity of 0.91, a positive predictive value of 0.89, a negative predictive value of 0.97, and an accuracy of 0.93. In 25% of the patients, the scan results led to alterations in patient management. F-NaF PET/CT for the evaluation of bone pain showed no explanation in 29%, benign pathology in 66%, and bone metastases in 5%. CONCLUSION: In the present cohort of patients with breast cancer, F-NaF PET/CT detected bone metastases in 42% with an accuracy of 0.93. The scan results led to a change in patient management in 25%. In the evaluation of bone pain, an explanation for pain was found in 71% of the scans.