18F-fluorocholine Positron Emission Research Articles

Theranostic modality by Nacl+Kcl solution on multiple metastatic prostate cancer: A clinical image

We report a case of multiple metastatic prostate cancer. A 63- year-old man presented with both paraplegia with anesthesia following transuretral resection of prostate (TUR-P). 18F-fluorocholine positron emission tomography-computed tomography

Role of 18F-FCH PET/CT in Detecting Recurrences of Prostate Cancer After Curative Treatments.

To evaluate the role of 18F-fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) in prostate cancer (PC) patients with biochemical recurrence who were submitted to different curative treatments. Seventy-five patients with PC who underwent 18F-FCH PET/CT for biochemical recurrence were retrospectively analyzed to distinguish patients who were submitted only to prostatectomy (PR group), only to radiotherapy (RT) on prostate with curative intent (RT group), and to both (PR + RT group). Correlations between 18F-FCH PET/CT and outcome and between prostate-specific antigen (PSA) values and sites and the number of metastases were analyzed. The performance of 18F-FCH PET/CT in relation to the PSA value and of maximum standardized uptake value (SUVmax) value in relation to patient outcome were assessed by receiver operating characteristic (ROC) curves. 18F-FCH PET/CT relapses mostly involved lymph nodes, bones, and prostate bed. K-cohen test showed moderate agreement with the outcome in the whole population and in the PR group, whereas in the RT group it was perfect and in PR + RT fair. A statistically significant difference in PSA values was observed in the presence of lymph node metastases and with multiple metastases. ROC curves showed PSA cut-off values of 1.96 ng/dL, 1.95, 1.81, and 2.96, respectively, in the whole population, PR, RT and PR + RT group. SUVmax cut-off values of 3.75, 3.45, and 4.7 were described in the whole population, PR group, and PR + RT group. The study confirms that 18F-FCH PET/CT is still valid in PC patients with suspected biochemical recurrence. Therefore, we can affirm that it still makes sense to perform it both with high PSA values and with lower values when prostate-specific membrane antigen tracers are not available.

Saengmaeksan, a traditional polyherbal formulation containing Panax ginseng, improves energy metabolism during exercise.

Saengmaeksan (SMS), a representative oriental medicine that contains Panax ginseng Meyer, Liriope muscari, and Schisandra chinensis (1:2:1), is used to improve body vitality and enhance physical activity. However, there is limited scientific evidence to validate the benefits of SMS. Here, we investigated the in vitro and in vivo regulatory effects of SMS and its constituents on energy metabolism and the underlying molecular mechanisms. For this, quantitative real-time polymerase chain reaction, 3D holotomographic microscopy, western blotting, and glucose uptake experiments using 18F-fluoro-2-deoxy-D-glucose (18F-FDG) were performed using L6 cells to investigate in vitro energy metabolism changes. In addition, 18F-fluorocholine (18F-FCH) and 18F-FDG positron emission tomography/computed tomography (PET/CT) analyses, immunohistochemistry, and respiratory gas analysis were performed in mice post-endurance exercise on a treadmill. In the energy metabolism of L6 cells, a significant reversal in glucose uptake was observed in the SMS-treated group, as opposed to an increase in uptake over time compared to the untreated control group. Furthermore, P. ginseng alone and SMS significantly decreased the volume of lipid droplets. SMS also regulated the phosphorylation of extracellular signal-regulated kinase (ERK), phosphorylation of p38, mitochondrial morphology, and the expression of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE/Ref-1) in H2O2-stimulated L6 cells. In addition, SMS treatment was found to regulate whole body and muscle energy metabolism in rats subjected to high-intensity exercise, as well as glucose and lipid metabolism in skeletal muscle. Therefore, SMS containing P. ginseng ameliorated imbalanced energy metabolism through oxidative stress-induced APE/Ref-1 expression. SMS may be a promising supplemental option for metabolic performance.

Preoperative identification of small parathyroid adenomas-better done by fluorocholine positron emission tomography/computed tomography.

Preoperative localization imaging studies are crucial for safe and successful parathyroidectomy in patients with primary hyperparathyroidism (pHPT), especially in focused approaches. A common imaging sequence is ultrasound followed by scintigraphy. These techniques, but not 18F-fluorocholine positron emission tomography/computed tomography (PET/CT), show lower detection rates in multiglandular disease (MGD), which is associated with smaller adenomas. In this study, we evaluate the accuracy of these modalities in small parathyroid adenomas (PAs) and discuss the potential sequence of preoperative localization diagnostics. Patients undergoing parathyroidectomy for pHPT were retrospectively categorized into small adenoma (specimen diameter <10 mm) and large adenoma. The groups were compared for accuracy of preoperative imaging studies, short-term and long-term outcomes. Among 147 patients retrospectively analyzed in this study, 38 small PAs were found. Preoperative correct quadrant prediction for small adenomas was significantly lower for ultrasound (P=0.03) and single-photon emission computed tomography/CT (SPECT/CT) (P<0.01) but not for choline PET/CT. While PET/CT was performed significantly more often in small PAs (P<0.01), it showed highly significant superiority over the other imaging modalities in accurate preoperative localization in both small (P<0.0001) and large PAs (P<0.01). There was no difference in calcium and parathyroid hormone (PTH) levels at latest follow-up with slightly more recurrences in small adenomas (P=0.08). Choline PET/CT showed a better diagnostic yield especially for small and multiple adenomas and was better in prediction of the correct localization. It could therefore serve as a second-line imaging modality.

Role of 18Fluorocholine Positron Emission Tomography/Computed Tomography in the Localization of Culprit Lesions in Patients of Persistent/Recurrent Primary Hyperparathyroidism: A Prospective Study in COVID Times.

Recurrent/persistent primary hyperparathyroidism in patients who have undergone previous parathyroidectomy is a challenging condition. Imaging is important for localizing the parathyroid adenoma for re-exploration and 18F-Fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) seems ideal for this purpose. This prospective study attempted to ascertain the utility of 18F-FCH PET/CT as an investigation in preoperative localization of abnormal parathyroid tissue in recurrent/persistent primary hyperparathyroidism while comparing it with 99mTc-Sestamibi dual-phase scintigraphy with early single-photon emission CT (SPECT)/CT and neck ultrasonography (USG). Twenty patients with biochemical features of recurrent/persistent primary hyperparathyroidism were enrolled into this study. They underwent neck USG, 99mTc-Sestamibi dual-phase scintigraphy with early SPECT/CT and 18F-FCH PET/CT for localization of parathyroid lesions. Six patients underwent surgical resection of the detected lesions, 3 were awaiting surgery, and 11 were managed conservatively. One patient died due to COVID. The calculated positive predictive values on a per-lesion basis of neck USG, 99mTc-sestamibi scintigraphy and early SPECT/CT and 18F-FCH PET/CT in the cohort of the 5 operated patients were 75% (3/4), 71.4% (5/7), and 71.4% (5/7), respectively. On a per-patient basis, the lesion detection rate was 100% for 99mTc-sestamibi scan and FCH PET (5/5) and 80% on neck USG (4/5). 18F-FCH PET/CT is a highly accurate imaging modality for the detection of parathyroid lesions in patients with recurrent/persistent primary hyperparathyroidism.

Comparison of Neck Ultrasonography, Dual Phase 99mTc-Sestamibi with early SPECT-CT & 18F-Fluorocholine PET-CT as First Line Imaging in Patients with Primary Hyperparathyroidism.

Successful surgical treatment for primary hyperparathyroidism requires accurate localization of abnormal parathyroid tissue in terms of location and number. Imaging is important for localizing the parathyroid adenoma, and there has been significant interest in 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) for this purpose. This study attempted to ascertain the utility of 18F-FCH PET/CT as a first-line investigation in preoperative localization of abnormal parathyroid tissue in primary hyperparathyroidism, in comparison with 99mTc-sestamibi dual-phase scintigraphy with early single-photon emission computed tomography (SPECT)/CT and neck ultrasonography. Fifty-five patients with biochemical features of primary hyperparathyroidism were enrolled in this study. They underwent neck ultrasonography, 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT, and 18F-FCH PET/CT for localization of parathyroid lesions. Thirty-three patients underwent surgical resection of the detected lesions. For two patients, clinical and biochemical follow-up was used as a gold standard. A total of 40 lesions were resected in the 33 patients who underwent surgery. A further two lesions were localized in two patients with clinical and biochemical follow-up as the gold standard. Of these 42 lesions, 41 were detected in preoperative imaging and 1 lesion was noted intraoperatively and resected. 41/42 lesions were detected by 18F-FCH PET/CT (detection rate: 97.6%), 33/42 by 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT (detection rate: 78.5%), and 30/42 by neck ultrasonography (detection rate: 71.4%). Detection rates on 18F-FCH PET/CT were superior to both 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT and neck ultrasonography in preoperative localization of parathyroid lesions in patients with primary hyperparathyroidism.

Detection of recurrence sites using 18F-fluorocholine PET/CT in prostate cancer patients with PSA failure.

The optimal condition for the clinical application of 18F-fluorocholine positron emission tomography-computed tomography (FCH-PET/CT) to detect recurrence sites in prostate-specific antigen (PSA) failure remains unclear due to the heterogeneity of prostate cancer failure. We aimed to evaluate the detection rate of FCH-PET/CT in prostate cancer patients with PSA failure and to determine the optimal PSA level for performing FCH-PET/CT. FCH-PET/CT was conducted in 89 patients diagnosed with PSA failure after radical treatment (radical prostatectomy in 75 and definitive radiotherapy in 14) between November 2018 and May 2021. Detection rates were examined via receiver operating characteristic (ROC) analysis, and multivariable logistic regression was performed to identify factors affecting positive FCH-PET/CT findings. We also conducted subgroup analyses according to the PSA failure patterns after the radical treatment (persistently high PSA [N=48] and biochemical recurrence [BCR] [N=41]). FCH-PET/CT demonstrated a 59.6% overall detection rate, and the optimal PSA threshold for detecting positive findings was ≥ 1.00ng/mL at the time of imaging. On multivariable analysis, PSA > 1.00ng/mL (P<0.001) was a significant predictor of positive FCH-PET/CT findings, especially regarding distant bone metastases (P<0.001) and recurrence outside the pelvis (P<0.001). In a subgroup analysis of patients with BCR after initial radical treatment, the area under the ROC curve (AUC) was 0.82, and PSA ≥ 1.75ng/mL was the optimal value for identifying positive FCH-PET/CT findings. This PSA value was also associated with significantly higher detection rates of distant bone metastases and outside-pelvis metastasis (P<0.001, both). FCH-PET/CT is a clinically useful tool for detecting tumor recurrence sites in prostate cancer patients with PSA failure if PSA has exceeded a certain value at the time of imaging. Particularly, higher AUC values were observed when FCH-PET/CT was performed in patients with BCR after initial treatment.

Usefulness of 18F-Fluorocholine Positron Emission Tomography-Computed Tomography in locating parathyroid adenomas in primary hyperparathyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Update on the current management of persistent and recurrent primary hyperparathyroidism after parathyroidectomy

Primary hyperparathyroidism (pHPT) is the third most common endocrine disease. The surgical procedure aims for permanent cure, but recurrence has been reported in 4%-10% of pHPT patients. Preoperative localization imaging is highly valuable. It includes ultrasound, computed tomography (CT), single-photon-emission CT, sestamibi scintigraphy and magnetic resonance imaging. The operation has been defined as successful when postoperative continuous eucalcemia exists for more than the first six months. Ongoing hypercalcemia during this period is defined as persistence, and recurrence is defined as hypercalcemia after six months of normocalcemia. Vitamin D is a crucial factor for a good outcome. Intraoperative parathyroid hormone (PTH) monitoring can safely predict the outcomes and should be suggested. PTH ≤ 40 pg/mL or the traditional decrease ≥ 50% from baseline minimizes the likelihood of persistence. Risk factors for persistence are hyperplasia and normal parathyroid tissue on histopathology. Risk factors for recurrence are cardiac history, obesity, endoscopic approach and low-volume center (at least 31 cases/year). Cases with double adenomas or four-gland hyperplasia have a greater likelihood of persistence/ recurrence. A 6-mo calcium > 9.7 mg/dL and eucalcemic parathyroid hormone elevation at 6 mo may be associated with recurrence necessitating long-term follow-up. 18F-fluorocholine positron emission tomography and 4-dimensional CT in persistent and recurrent cases can be valuable before reoperation. With these novel advances in preoperative imaging and localization as well as intraoperative PTH measurement, the recurrence rate has dropped to 2.5%-5%. Six-month serum calcium ≥ 9.8 mg/dL and parathyroid hormone ≥ 80 pg/mL indicate a risk of recurrence. Negative sestamibi scintigraphy, diabetes and elevated osteocalcin levels are predictors of multiglandular disease, which brings an increased risk of persistence and recurrence. Bilateral neck exploration was considered the gold-standard diagnostic method. Minimally invasive parathyroidectomy and neck exploration are both effective surgical techniques. Multidisciplinary diagnostic and surgical management is required to prevent persistence and recurrence. Long-term follow-up, even up to 10 years, is necessary.

18F-fluorocholine PET/CT semi-quantitative analysis in patients affected by primary hyperparathyroidism: a comparison between laboratory and functional data.

This retrospective study aims to establish 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) performance in finding hyperfunctioning parathyroid glands, analyze a potential role for semi-quantitative PET parameters and assess factors that may influence PET/CT outcome. Forty patients with suspect primary hyperparathyroidism (pHPT) and negative/equivocal conventional imaging underwent FCH-PET/CT in our Institution. For every lesion, visual and semi-quantitative analyses were performed on PET/CT images. In qualitative analysis, a lesion was considered positive if a clear focus of uptake, significantly higher than normal thyroid tissue, was identifiable. Ectopic focal uptake was also regarded as positive PET result. Lesion SUVMax was measured by assigning a spheric VOI to the suspect area of uptake. Thyroid SUVMean was assessed by placing a spheric VOI inside the contralateral thyroid lobe, and SUVratio was calculated using this background region. All patients were subsequently submitted to surgery and histopathologic workup. Sensitivity, positive predictive value (PPV) and accuracy were calculated based on histopathologic reports for every lesion. Pearson's test was used to assess a correlation between laboratory and histopathologic features with SUVr. Four out of the 40 patients who underwent surgery for pHPT had more than one histologic proven unhealthy parathyroid and three had papillary thyroid cancer (PTC). A total of 48 lesions were analyzed. We found 42/48 lesions (87.5%) to have true-positive uptake, whereas three lesions (6.7%) had false-positive uptake (PTC). Three histologic proven parathyroid adenomas showed no uptake (6.7%); the sensitivity/PPV were 93.3% and accuracy was 87,8%. Pearson's test showed a significant correlation between PTH values and parathyroid size with SUVr values (r = 0.56 and 0.55, respectively, p < 0.01 for both features). As stated in recent literature, we observed excellent diagnostic sensitivity of FCH-PET/CT in patients with pHPT, providing surgeons a fine tool to optimize treatment. More studies are needed to improve the evaluability of semi-quantitative parameters towards a further improvement of diagnostic accuracy.

Preoperative Imaging with [18F]-Fluorocholine PET/CT in Primary Hyperparathyroidism.

Primary hyperparathyroidism (pHPT) is a common endocrine disorder due to hyperfunctioning parathyroid glands. To date, the only curing therapy is surgical removal of the dysfunctional gland, making correct detection and localization crucial in order to perform a minimally invasive parathyroidectomy. 18F-Fluorocholine positron emission tomography/computed tomography (18F-FCH PET/CT) has shown promising results for the detection of pHPT, suggesting superiority over conventional imaging with ultrasounds or scintigraphy. A total of 33 patients with pHPT who had negative or equivocal findings in conventional imaging received 18F-FCH PET/CT preoperatively and were retrospectively included. A pathological hyperfunctional parathyroid gland was diagnosed in 24 cases (positive PET, 72.7%), 4 cases showed equivocal choline uptake (equivocal PET, 12.1%), and in 5 cases, no enhanced choline uptake was evident (negative PET, 15.2%). Twelve of the twenty-four detected adenoma patients underwent surgery, and in all cases, a pathological parathyroid adenoma was resected at the site detected by PET/CT. Two of the six patients without pathological choline uptake who received a parathyroidectomy revealed no evidence of parathyroid adenoma tissue in the histopathological evaluation. This retrospective study analyzes 18F-FCH PET/CT in a challenging patient cohort with pHPT and negative or equivocal conventional imaging results and supports the use of 18F-FCH for the diagnosis of hyperfunctional parathyroid tissue, especially in this patient setting, with a 100% true positive and true negative detection rate. Our study further demonstrates the importance of 18F-FCH PET/CT for successful surgical guidance.

Feasibility of 18F-Fluorocholine PET for Evaluating Skeletal Muscle Atrophy in a Starved Rat Model.

Imaging techniques for diagnosing muscle atrophy and sarcopenia remain insufficient, although various advanced diagnostic methods have been established. We explored the feasibility of 18F-fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) for evaluating skeletal muscle atrophy, as an imaging technique that tracks choline level changes in muscles. Cell uptake in L6 cells by 18F-FCH was performed in a complete medium containing serum (untreated group, UN) and a serum-free medium (starved group, ST). Small-animal-dedicated PET/CT imaging with 18F-FCH was examined in in-vivo models with rats that were starved for 2 days to cause muscle atrophy. After the hind limbs were dissected, starvation-induced in-vivo models were anatomically confirmed by reverse-transcription polymerase chain reaction to evaluate the expression levels of the atrophy markers muscle RING-finger protein-1 (MuRF-1) and atrogin-1. 18F-FCH uptake was lower in the starvation-induced cells than in the untreated group, and in-vivo PET uptake also revealed a similar tendency (the average standardized uptake value (SUVmean) = 0.26 ± 0.06 versus 0.37 ± 0.07, respectively). Furthermore, the expression levels of MuRF-1 and atrogin-1 mRNA were significantly increased in the starvation-induced muscle atrophy of rats compared to the untreated group. 18F-FCH PET/CT may be a promising tool for diagnosing skeletal muscle atrophy.

Detection of a second primary cancer in a 18F-fluorocholine PET/CT – multicentre retrospective analysis on a group of 1345 prostate cancer patients

Aim of this study was to evaluate the rate of incidental detection of second primary cancer (SPC) at 18F-fluorocholine ([18F]FCH) positron emission tomography/computed tomography (PET/CT) performed in prostate cancer patients.A retrospective analysis was performed on a group of 1345 prostate cancer patients, who underwent [18F]FCH PET/CT study because of suspicion of recurrence (n = 937) or for initial staging (n = 408). Images were acquired after intravenous injection [18F]FCH with a mean activity of 200 ± 75 MBq (5.4 ± 2 mCi), from the top of the head to the half of the thigh. The confirmation of second primary cancer was obtained from the cancer registry.Based on the [18F]FCH PET/CT scans, a second primary cancer was suspected in 89 patients (6.6%). Of these, a malignancy was histologically confirmed in 26 patients (29% of all suspected findings and 1.9% of the complete cohort). Lung cancer (including adenocarcinoma, neuroendocrine cancer) was diagnosed in 13 patients (50%) and hematologic neoplasm (including chronic lymphocytic leukemia, Hodgkin lymphoma, follicular lymphoma, and multiple myeloma) in 5 patients (19%). 18F-fluorocholine PET/CT also revealed esophageal cancer, mesothelioma, testicular, renal, bladder, and colorectal cancer inindividual patients, non-keratinizing squamous cell carcinoma (SCC) of the skin as well as head and neck SCC with unknown primary.We conclude that incidental detection of a second primary cancer in prostate cancer patients using [18F]FCH PET/CT is not very common and that lung cancer and hematologic malignancies are most frequently detected.

DIAGNOSTIC PERFORMANCES OF 18F-FLUOROCHOLINE POSITRON EMISSION TOMOGRAPHY-COMPUTED TOMOGRAPHY AND REPEATED ULTRASONOGRAPHY IN DETECTING UNDEFINED LESIONS IN PATIENTS WITH AN INDICATION FOR PRIMARY HYPERPARATHYROIDISM SURGERY.

18F-fluorocholine (FCH) has been used as a positron emission tomography (PET) tracer in the localization of hyper-functioning parathyroid glands (HPGs). We performed this methodological study to evaluate the diagnostic performance of 18F-FCH PET/computerized tomography (CT) and repeated ultrasonography (USG) in detecting unidentified lesions in patients with primary hyperparathyroidism (PHPT). In this retrospective methodological study, we studied the diagnostic performance of 18F-FCH PET/CT and a repeated USG in detecting unidentified parathyroid lesions. Twenty-eight patients who were diagnosed with PHPT, had an indication for surgery following the current guidelines and had no identified lesion on 99mTc-MIBI SPECT/CT, USG, or other imaging methods than 18F-FCH PET/CT, included in the study. While lesions were detected in 26 patients via 18F-FCH PET/CT among 28 patients [92.9% (95% CI: 76.6%-99.1%)], the lesion detection rate was 95.7% (95% CI: 78.1%-99.9%) in 23 patients who underwent a repeated USG. The sensitivity and the accuracy of both 18F-FCH PET/CT and repeated USG were 95.2% (95% CI: 76.2%-99.9%) and 95.0 (95% CI: 75.1%-99.9%), respectively. This study supports that the combination of 18F-FCH PET/CT and repeated USG has promising potential for being an imaging technique for early detection and localization of HPGs.

Detectability of 18F-choline PET/MR in primary hyperparathyroidism.

We aimed to evaluate the power of 18F-fluorocholine (FCH) positron emission tomography/magnetic resonance (PET/MR) imaging in unlocalized primary hyperparathyroidism. Thirty-four patients were included. In 17/34 patients, PET/MR was performed immediately after a negative 18F-FCH PET/CT. Sensitivity, specificity, positive and negative predictive values were calculated for MR only (blinded to PET data) and PET only (blinded to MR data) findings. 18F-FCH PET/MR was positive in 26/34 (76%) patients. PET/MR was also positive in 12/17 (71%) patients with a negative PET/CT. Among 11/34 (32%) patients where 18F-FCH PET-only and MR-only results were discordant, MR was false positive in 7/11 patients (3/7 of the lesions were not 18F-FCH avid and in 4/7 of them PET and MRI pointed different locations. Postoperative histopathology revealed that 18F-FCH-positive ones were true positives). Sensitivity, specificity, PPV, NPV and accuracy of neck MR evaluated blinded to PET data were 80%, 50%, 70%, 64% and 68%, respectively, and all were calculated as 100% for PET/MR. 18F-FCH PET/MR is very effective in preoperative localization of parathyroid adenomas even if 18F-FCH PET/CT is negative. Neck MR alone is insufficient in detecting parathyroid adenomas but PET/MR combination helps in precise localisation.

A cost-utility analysis of 18F-fluorocholine–positron emission tomography imaging for localizing primary hyperparathyroidism in the United States

BackgroundPrimary hyperparathyroidism historically necessitated bilateral neck exploration to remove abnormal parathyroid tissue. Improved localization allows for focused parathyroidectomy with lower complication risks. Recently, positron emission tomography using radiolabeled 18F-fluorocholine demonstrated high accuracy in detecting these lesions, but its cost-effectiveness has not been studied in the United States. MethodsA decision tree modeled patients who underwent parathyroidectomy for primary hyperparathyroidism using single preoperative localization modalities: (1) positron emission tomography using radiolabeled 18F-fluorocholine, (2) 4-dimensional computed tomography, (3) ultrasound, and (4) sestamibi single photon emission computed tomography (SPECT). All patients underwent either focused parathyroidectomy versus bilateral neck exploration, with associated cost ($) and clinical outcomes measured in quality-adjusted life-years gained. Model parameters were informed by literature review and Medicare costs. Incremental cost-utility ratios were calculated in US dollars/quality-adjusted life-years gained, with a willingness-to-pay threshold set at $100,000/quality-adjusted life-year. One-way, 2-way, and threshold sensitivity analyses were performed. ResultsPositron emission tomography using radiolabeled 18F-fluorocholine gained the most quality-adjusted life-years (23.9) and was the costliest ($2,096), with a total treatment cost of $11,245 or $470/quality-adjusted life-year gained. Sestamibi single photon emission computed tomography and ultrasound were dominated strategies. Compared with 4-dimentional computed tomography, the incremental cost-utility ratio for positron emission tomography using radiolabeled 18F-fluorocholine was $91,066/quality-adjusted life-year gained in our base case analysis, which was below the willingness-to-pay threshold. In 1-way sensitivity analysis, the incremental cost-utility ratio was sensitive to test accuracy, positron emission tomography using radiolabeled 18F-fluorocholine price, postoperative complication probabilities, proportion of bilateral neck exploration patients needing overnight hospitalization, and life expectancy. ConclusionOur model elucidates scenarios in which positron emission tomography using radiolabeled 18F-fluorocholine can potentially be a cost-effective imaging option for primary hyperparathyroidism in the United States. Further investigation is needed to determine the maximal cost-effectiveness for positron emission tomography using radiolabeled 18F-fluorocholine in selected populations.

Superior sensitivity of 18F-fluorocholine: PET localization in primary hyperparathyroidism

BackgroundPreoperative parathyroid imaging guides surgeons during parathyroidectomy. This study evaluates the clinical impact of 18F-fluorocholine positron emission tomography for preoperative parathyroid localization on patients with primary hyperparathyroidism. MethodsPatients with primary hyperparathyroidism and indications for parathyroidectomy had simultaneous 18F-fluorocholine positron emission tomography imaging/magnetic resonance imaging. In patients who underwent subsequent parathyroidectomy, cure was based on lab values at least 6 months after surgery. Location-based sensitivity and specificity of 18F-fluorocholine positron emission tomography imaging was assessed using 3 anatomic locations (left neck, right neck, and mediastinum), with surgery as the gold standard. ResultsIn 101 patients, 18F-fluorocholine positron emission tomography localized at least 1 candidate lesion in 93% of patients overall and in 91% of patients with previously negative imaging, leading to a change in preoperative strategy in 60% of patients. Of 76 patients who underwent parathyroidectomy, 58 (77%) had laboratory data at least 6 months postoperatively, with 55/58 patients (95%) demonstrating cure. 18F-fluorocholine positron emission tomography successfully guided curative surgery in 48/58 (83%) patients, compared with 20/57 (35%) based on ultrasound and 13/55 (24%) based on sestamibi. In a location-based analysis, sensitivity of 18F-fluorocholine positron emission tomography (88.9%) outperformed both ultrasound (37.1%) and sestamibi (27.5%), as well as ultrasound and sestamibi combined (47.8%). ConclusionLong-term results in the first cohort in the United States to use 18F-fluorocholine positron emission tomography for parathyroid localization confirm its utility in a challenging cohort, with better sensitivity than ultrasound or sestamibi.

18F-Fluorocholine Positron Emission Tomography/Computed Tomography is a Highly Sensitive but Poorly Specific Tool for Identifying Malignancy in Thyroid Nodules with Indeterminate Cytology: The Chocolate Study.

Background: Refining the risk of malignancy in patients presenting with thyroid nodules with indeterminate cytology (IC) is a critical challenge. We investigated the performances of 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) to predict malignancy.Methods: Between May 2016 and March 2019, 107 patients presenting with a thyroid nodule ≥15 mm with IC and eligible for surgery were included in this prospective study. Head-and-neck PET/CT acquisitions were performed 20 and 60 minutes after injection of 1.5 MBq/kg of FCH. PET/CT acquisition was scored positive when maximal standardized uptake value in the IC nodule was higher than in the thyroid background. Pathology was the gold standard for diagnosis.Results: At pathology, 19 (18%) nodules were malignant, 87 were benign, and one was a noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Sensitivity, specificity, accuracy, positive-predictive value (PPV), and negative-predictive value (NPV) of FCH PET/CT in detecting cancer or NIFTP were 90%, 50%, 55%, 29%, and 96% at 20 minutes and 85%, 49%, 67%, 28%, and 94% at 60 minutes, respectively. Higher specificity (58% vs. 33%, p = 0.01) was observed in nononcocytic (n = 72) than in oncocytic IC nodules (n = 35). The pre-PET/CT probability of cancer or NIFTP in Bethesda III–IV nodules was 11% and the post-PET/CT probability was 19% in PET-positives and 0% in PET-negatives. In retrospective analysis, 42% of surgeries would have been unnecessary after PET/CT and 81% before (p < 0.001), resulting in a hypothetical 48% reduction (95% confidence interval [32–64]).Conclusions: FCH PET/CT offers high NPV to reliably exclude cancer in PET-negative IC nodules, but suffers from low PPV, particularly in those with oncocytic cytology. ClinicalTrials.gov identifier: NCT02784223.

Combining molecular and functional imaging in metastatic castration-resistant prostate cancer (mCRPC).

141 Background: Recently, plasma tumour DNA (ptDNA) has been identified as a potential early noninvasive biomarker of treatment response in mCRPC patients ( Conteduca, Br J Cancer 2020). In this study, we sought to determine whether pre-treatment ptDNA could accurately reflect metabolic tumor burden in mCRPC and if it could be in combination with functional imaging could provide better prognostication. Methods: Between October 2011 and June 2016, 102 plasma samples from mCRPC patients treated with abiraterone or enzalutamide were collected. Targeted next-generation sequencing was performed to determine baseline ptDNA fraction. Maximum standardized uptake value (SUVmax), total lesion activity (TLA), and metabolic tumour volume (MTV) were calculated on 18F-fluorocholine positron emission tomography/computed tomography. A Weibull multiple regression model was adopted to evaluate the combined impact of clinical, molecular and imaging features on overall survival (OS) and to obtain a prognostic score. Each variable was allotted a “partial score” that depended on the size of the regression coefficient. Total scores ranged between 0 and 5.85 and assigned patients to 3 different risk groups according to 18-months survival probability: group I, &gt;70%; group II 30%-70%; and group III, &lt;30%. We estimated OS probabilities by the exponential model and by the Kaplan-Meier method. Results: We observed a significant association between ptDNA levels dichotomized as below or above median plasma tumor fraction (low ptDNA≤0.188 versus high ptDNA&gt;0.188) and median SUVmax (p&lt;0.0001), MTV (p=0.0005) and TLA (p&lt;0.0001). Patients were randomly divided into a training set (n=68) and a validation set (n=34). In the training cohort, we performed a multivariable analysis showing that visceral metastasis, serum LDH, MTV and ptDNA were independent predictors of OS [HR=2.64, 95%CI 1.32-5.26, p=0.006; HR=3.69, 95%CI 1.98-6.87, p&lt;0.0001; HR=1.91, 95%CI 1.13-3.21, p=0.015; and HR=2.64, 95%CI 1.32-5.26, p=0.003, respectively]. In the training set, median OS was significantly different among the 3 risk groups (risk group I, 29.2 months [95% CI, 18.3 to 37.0 months]; risk group II, 15.9 months [95% CI, 10.6 to 24.0 months]; and risk group III, 8.7 months [95% CI, 6.3 to 15.4 months]; p&lt;0.0001). Similar results were observed in the validation set groups (risk group I, 23.4 months [95% CI, 8.1 to 38.5 months]; risk group II, 13.3 months [95% CI, 3.7 to 18.0 months]; and risk group III, 7.3 months [95% CI, 2.6 to 11.8 months]; p=0.001). Conclusions: Integrating plasma DNA analysis with functional imaging may improve prognostic risk stratification and treatment selection in mCRPC patients. A larger prospective evaluation is now warranted.

Misleading localization by 18F-fluorocholine PET/CT in familial hypocalciuric hypercalcemia type-3: a case report

BackgroundFamilial hypocalciuric hypercalcemia (FHH) is a heterogeneous autosomal-dominant disorder of calcium hemostasis that may be difficult to distinguish clinically from mild primary hyperparathyroidism. Loss-of-function mutations mainly involving Arg15 residue of the adaptor-related protein complex 2, sigma subunit 1 (AP2S1) cause a rarer, more recently recognized form of FHH, FFH type-3. Recently, 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) showed superior sensitivity to conventional imaging in localizing parathyroid adenomas. We report a new FFH type-3 patient who underwent unnecessary parathyroidectomy in association with misleading FCH-PET/CT imaging.Case presentationA 29-year old woman was initially evaluated for parathyroid hormone (PTH)-dependent hypercalcemia in 2013. Medical history was positive only for chronic constipation and malaise with no personal or family history of hypercalcemia, kidney stones, or neck surgery. Over seven years, serum calcium level was 2.51–2.89 mmol/L with concomitant PTH level of 58.7–94.8 mmol/L. Serum phosphate levels were in the low/low normal range. Serum creatinine and magnesium levels were normal. 25-hydroxy vitamin D level was 13 nmol/L. 24-hour urine calcium level was 1.92 mmol/day but increased to 6.99 mmol/day after treatment with cholecalciferol 1000 IU daily. Bone mineral density and renal ultrasound were normal. Parathyroid ultrasound showed two hypoechoic nodules inferior to the left and right thyroid lobes; however, 99mtechnitium-sestamibi scans (2013, 2016, 2018) were negative. FCH-PET/CT (2019) showed focal uptake co-localizing with the nodule inferior to the left thyroid lobe. The patient underwent left inferior parathyroidectomy and pathology was consistent with parathyroid hyperplasia. However, postoperatively, serum calcium and PTH levels remained elevated and FCH-PET/CT and ultrasound showed persistence of the uptake/nodule. Whole exome sequencing showed Arg15Cys mutation in the AP2S1 gene characteristic of FHH type-3.ConclusionsIn this new case of FHH type-3, FCH-PET/CT failed to localize to the hyperplastic parathyroid glands and localized instead to apparently a lymph node. This, together with increased urinary calcium after vitamin D supplementation, led to unnecessary parathyroidectomy. Given the increasingly lower cost of genetic testing and the cost of follow up and unnecessary surgery, it may prudent to include genetic testing for FHH early on in patients with mild PTH-dependent hypercalcemia.