Refining the role of presurgical PET/4D-CT in a large series of patients with primary hyperparathyroidism undergoing [18F]Fluorocholine PET/CT.

BACKGROUND: 4D-CT has garnered attention as complementary imaging for patients with primary hyperparathyroidism (pHPT). Herein we evaluated a diagnostic strategy using [18F]Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT), followed by 4D-CT integrated into PET/4D-CT after negative/inconclusive PET/CT results in a single-center retrospective cohort of 166 pHPT patients who underwent parathyroidectomy after [18F]Fluorocholine PET/4D-CT. METHODS: PET/CT and 4D-CT images were interpreted by three nuclear medicine physicians and one expert radiologist. Pathological findings were documented, and concordance rates were assessed. PET/CT results were categorized as positive/negative, with positive cases rated on a 3-level certitude scale: low, moderate, high. Inconclusive cases included low/moderate positivity. The added value of PET/4D-CT was assessed for negative/inconclusive cases through joint reading. RESULTS: PET/CT lesion-based analysis showed almost perfect interobserver concordance (Cohen's kappa >.8). Across the cohort, PET/CT had a sensitivity of 83%, specificity of 97%, PPV of 90% and NPV of 94%. For 4D-CT, these values were sensitivity: 53%, specificity: 84%, PPV: 56% and NPV: 82%. PET/CT was significantly more accurate than 4D-CT. Among 44 patients with negative/inconclusive results, PET/CT had sensitivity: 60%, specificity: 91%, PPV: 71% and NPV: 86%. In the same patients, sensitivity and specificity of the sequential diagnostic algorithm increased to 80% and 97%, showing significantly better global accuracy (92% vs. 83%) than standard PET/CT. CONCLUSIONS: We support a personalized imaging algorithm for pHPT, placing [18F]Fluorocholine PET/CT at the forefront, followed by 4D-CT integrated into PET/4D-CT in the same imaging session for negative/inconclusive results. When PET/CT results are clearly positive, the additional sensitivity benefit of 4D-CT is minimal.

Performance of [18F]fluorocholine PET/CT in MEN1-related primary hyperparathyroidism before initial surgery or for persistent/recurrent disease.

PURPOSE: The aims of the study were to evaluate the performance and robustness of [18F]fluorocholine PET/CT in detecting hyperfunctioning parathyroid glands in MEN1-related primary hyperparathyroidism (pHPT) at different stages of their disease. METHODS: Retrospective French multicenter study including patients with MEN1 pHPT who underwent [18F]fluorocholine PET/CT at initial diagnosis or for evaluation of persistent/recurrent disease. PET/CT were independently reviewed by two readers in a blinded manner. The assessment of PET/CT on a per-patient basis was assessed using a comprehensive set of criteria that considered pathological findings or agreement with alternative diagnostic methods in non-operated patients. The secondary objectives included the analysis of the performance of PET/CT at a per-lesion level, with reference to a pathological Gold Standard, and examining its interobserver reproducibility. RESULTS: A total of 71 MEN1 patients were included (73 PET/CT) in the study. At the per-patient level (entire cohort), [18F]fluorocholine PET/CT sensitivity ranged from 98.5 to 100% among the different readers. An average of 1.77 glands per PET was described, with 2.35 glands at the initial diagnosis (n = 23) and 1.5 in previously operated cases (n = 50). PET/CT detected more lesions than conventional imaging work-up (neck ultrasound and/or scintigraphy). At the per-lesion level (41 operated patients), sensitivity ranged across different readers from 84.4 to 87%, and specificity ranged from 94.7 to 98.8%. At initial diagnosis, all patients that exhibited 3 or more abnormal glands on PET underwent subtotal parathyroidectomy while 7 out of 13 patients with 1 or 2 gland abnormalities on PET underwent less than subtotal parathyroidectomy. Finally, the degree of inter-observer agreement was high. CONCLUSION: [18F]fluorocholine PET/CT is a reliable and robust imaging modality for the evaluation of MEN1-related pHPT and could guide surgeons in achieving the optimal benefit-risk ratio. This study gives a great impetus for its adoption as a primary diagnostic tool in this context.

64CuCl2 PET Imaging of 4T1-Related Allograft of Triple-Negative Breast Cancer in Mice.

64CuCl2 is an economic radiotracer for oncologic PET investigations. In the present study, we characterized the uptake of 64CuCl2 in vivo by µPET/CT in an allograft 4T1-related mouse model (BALB/c) of advanced breast cancer. 18F-FDG was used as a comparator. Twenty-two animals were imaged 7-9 days following 4T1-cell implantation inside mammary glands. Dynamic 64CuCl2 µPET/CT acquisition or iterative static images up to 8 h p.i. were performed. Animal biodistribution and tumor uptake were first evaluated in vivo by µPET analysis and then assessed on tissue specimens. Concerning 18F-FDG µPET, a static acquisition was performed at 15 min and 60 min p.i. Tumor 64CuCl2 accumulation increased from 5 min to 4 h p.i., reaching a maximum value of 5.0 ± 0.20 %ID/g. Liver, brain, and muscle 64CuCl2 accumulation was stable over time. The tumor-to-muscle ratio remained stable from 1 to 8 h p.i., ranging from 3.0 to 3.7. Ex vivo data were consistent with in vivo estimations. The 18F-FDG tumor accumulation was 8.82 ± 1.03 %ID/g, and the tumor-to-muscle ratio was 4.54 ± 1.11. 64CuCl2 PET/CT provides good characterization of the 4T1-related breast cancer model and allows for exploration of non-glycolytic cellular pathways potentially of interest for theragnostic strategies.

Diffuse Bone Uptake of 131 I and Effect on Blood Counts in a Patient With Papillary Thyroid Carcinoma and Chronic Lymphocytic Leukemia.

ABSTRACT: A 57-year-old woman with history of chronic lymphocytic leukemia was referred to our center for adjuvant 131 I therapy following complete thyroidectomy for differentiated thyroid cancer. Posttherapeutic scintigraphy revealed atypical diffuse osteomedullar uptake. A major drop in lymphocyte count was observed, from 117.7 g/L to 4.8 g/L 8 weeks after 131 I therapy. Bone marrow uptake is presumed to be related to tracer sequestration in leukemic cells. White blood cell count normalization suggests a high sensitivity of leukemic cells to beta emission. This scintigraphic pattern may act as a pitfall for nuclear medicine physician.

Bilateral Ovarian Metastases of Hepatocellular Carcinoma Diagnosed with 18F-Fluorocholine PET/CT in a Patient with Endometriosis.

A 47-year-old woman with history of hepatocellular carcinoma was referred for 18F-fluorocholine PET/CT evaluation due to elevated alpha-fetoprotein. The examination showed several peritoneal uptakes and two nodular pelvic foci. Coelioscopic exploration allowed confirmation and resection of multiple peritoneal metastases from hepatocellular carcinoma while pelvic biopsies revealed endometriosis and endosalpingiosis. However, alpha-fetoprotein kept rising: subsequent 18F-fluorodesoxyglucose PET/CT exploration found no pelvic uptake, while 18F-fluorocholine PET/CT revealed intense tracer accumulation in the two pelvic masses corresponding to bilateral ovarian metastases of hepatocellular carcinoma. We highlight the importance of 18F-fluorocholine PET/CT in hepatocellular carcinoma especially in patients with confounding comorbidities such as endometriosis.

Does 18F-Fluorocholine PET/CT add value to positive parathyroid scintigraphy in the presurgical assessment of primary hyperparathyroidism?

Introduction: To investigate the value of presurgical 18F-FCH PET/CT in detecting additional hyperfunctioning parathyroids despite a positive 99mTc-sestamibi parathyroid scintigraphy in patients with primary hyperparathyroidism (pHPT). Methods: This is a retrospective study involving patients with pHPT, positive parathyroid scintigraphy performed before 18F-FCH PET/CT, and parathyroid surgery achieved after PET/CT. Imaging procedures were performed according to the EANM practice guidelines. Images were qualitatively interpreted as positive or negative. The number of pathological findings, their topography, and ectopic location were recorded. Histopathology, Miami criterion, and biological follow-up were considered to ensure effective parathyroidectomy confirming the complete excision of all hyperfunctioning glands. The impact of 18F-FCH PET/CT on therapeutic strategy was recorded. Results: 64/632 scanned pHPT patients (10%) were included in the analysis. According to a per lesion-based analysis, sensitivity, specificity, positive predictive value, and negative predictive value of 99mTc-sestamibi scintigraphy were 82, 95, 87, and 93%, respectively. The same values for 18F-FCH PET/CT were 93, 99, 99, and 97%, respectively. 18F-FCH PET/CT showed a significantly higher global accuracy than 99mTc-sestamibi scintigraphy: 98% (CI: 95-99) vs. 91% (CI: 87-94%). Youden Index was 0.79 and 0.92 for 99mTc-sestamibi scintigraphy and 18F-FCH PET/CT, respectively. Scintigraphy and PET/CT were discordant in 13/64 (20%) patients (49 glands). 18F-FCH PET/CT identified nine pathologic parathyroids not detected by 99mTc-sestamibi scintigraphy in 8 patients (12.5%). Moreover, 18F-FCH PET/CT allowed the reconsideration of false-positive scintigraphic diagnosis (scinti+/PET-) for 8 parathyroids in 7 patients (11%). The 18F-FCH PET/CT influenced the surgical strategy in 7 cases (11% of the study population). Conclusion: In a preoperative setting, 18F-FCH PET/CT seems more accurate and useful than 99mTc-sestamibi scan in pHPT patients with positive scintigraphic results. Positive parathyroid scintigraphy could be not satisfactory before neck surgery particularly in patients with multiglandular disease, suggesting a need to evolve the practice and define new preoperative imaging algorithms including 18F-FCH PET/CT at the fore-front in pHPT patients.

Impact of pelvic dynamic acquisition on final reading of 18 F-Fluorocholine positron emission tomography in patients with prostate adenocarcinoma: True need or unnecessary burden?

INTRODUCTION: Despite the increasing use of 18 F-fluorocholine (18 F-FCH) positron emission tomography (PET) in patients with prostate cancer, the acquisition protocol remains debated. We have evaluated the influence of the pelvic dynamic phase on the final reading of whole-body 18 F-FCH PET, to assess the need for a two-stage protocol. Reading the physician's experience and patient's previous treatment profile was also considered as potential influencing factors on final PET interpretation. METHODS: All 18 F-FCH PET/CT performed from January 2018 to September 2019 in patients with prostate cancer and including a pelvic dynamic phase followed by a delayed whole-body acquisition were retrospectively retrieved. PET/CT were analysed by one expert nuclear medicine physician and one resident. The whole-body scan was analysed blinded (first reading) and nonblinded from the results of the dynamic phase. RESULTS: 221 consecutive PET/CT were selected from 201 patients previously treated by radical prostatectomy (n = 31), pelvic radiation therapy (n = 60), or both (n = 94). 24 patients had no previous treatments, and 12 benefited from other focal treatments. In the whole population, dynamic acquisition modified final interpretation of 32/221 scans (14.5%) for residents, 26 (11.8%) for experts and 19 (8.6%) for consensual reading. No influence of previous treatments was found. The availability of a dynamic phase would have been responsible for treatment modification in 5/221 scans (2.3%). Considering only the prostate bed, dynamic acquisition modified the final interpretation in 7/125 (5.6%) studies (consensual reading) from patients with previous prostatic surgery and 4/84 (4.8%) scans from patients without a history of prostatic surgical intervention. No significant influence of dynamic acquisition was found on the final PET interpretation on prostate lodge accordingly to previous prostatic surgery. CONCLUSION: The dynamic phase changes the interpretation of 18 F-FCH PET in about 9% of cases and the therapeutic strategy in <3% of patients. The influence of the early phase reduces with physician experience. Patient's treatment profile does not appear to have a significant influence on the variability of interpretation, also including the prostate bed.

18F-Fluorocholine PET and 4D-CT in Patients with Persistent and Recurrent Primary Hyperparathyroidism.

Patients with primary hyperparathyroidism (pHPT) can develop persistent (P-pHPT) or recurrent (R-pHPT) disease after parathyroidectomy. Before recommending reoperation, recurrence must be accurately identified because of the high risk of complications. Our study evaluates 18F-fluorocholine (18F-FCH) PET/CT and 4D-CT integrated in PET/4D-CT in patients with P-pHPT/R-pHPT. Patients with P-pHPT/R-pHPT investigated by 18F-FCH PET/4D-CT between May 2018 and March 2021 were retrospectively included. Forty-two patients were included, 37 of whom underwent 4D-CT. The sensitivity and detection rate (DR%) were 95% and 88% for 18F-FCH PET/CT and 70% and 63% for 4D-CT, respectively. PET/CT and 4D-CT were concordant in 18/24 glands and concordant and positive in 15/24 (63%) glands. Discordant results were obtained for 6/24 glands. The surgical success rate was 65%. PET/CT showed significantly higher sensitivity than 4D-CT. Dynamic CT allowed the identification of no additional glands missed by PET/CT, and the combination of the 2 techniques did not improve the sensitivity or DR%. 18F-FCH PET/CT appears to be a valuable technique to accurately detect hyperfunctioning parathyroid tissue in patients with P-pHPT/R-pHPT and is better than 4D-CT. Except for cases with doubtful locations of PET targets that may require 4D-CT for surgical guidance, standard nonenhanced 18F-FCH PET/CT can be effectively recommended in patients with P-pHPT/R-pHPT before reoperation.

Dual-Time-Point 18F-Fluorocholine PET/CT Improves Characterization of Thyroid Nodules in Patients Referred for Primary Hyperparathyroidism: A Proof of Concept Study.

PURPOSE: Thyroid nodules frequently coexist with primary hyperparathyroidism (pHPT). Because of the increasing use of 18F-fluorocholine (18F-FCH) PET/CT in patients with pHPT, evaluation of its clinical utility for thyroid nodules characterization in this population is of paramount importance. Herein, we investigate the value of dual-point 18F-FCH PET/CT in the diagnosis of thyroid cancer in patients referred for pHPT imaging who have thyroid nodules. PATIENTS AND METHODS: All pHPT patients who underwent a dual-time point 18F-FCH PET/CT (at 5 and 60 minutes postinjection) between July 2019 and December 2020 were analyzed. Only those with a thyroid nodule greater than 10-mm and pathological analysis (criterion standard) were included. Nodule-to-thyroid SUVmax ratio was calculated at the 2 study points, as well as the 18F-FCH washout index (WO%). RESULTS: Twenty-seven patients (32 nodules) were included in this study. The final diagnoses were as follows: 27 benign nodules including 2 NIFTPs (noninvasive follicular thyroid neoplasm with papillary-like nuclear features) and 5 cancers of follicular origin. Early uptake ratio was significantly higher in malignant lesions than in benign nodules (P = 0.0008). Thyroid cancers were also characterized by a marked 18F-FCH washout index (WO% benign vs cancer: 2.9% ± 4.1% vs 45.5% ± 13.4%, P = 0.0001). Using a WO% threshold of 22.1%, 25/27 benign nodules and 5/5 malignant lesions were accurately classified (sensitivity of 100%, specificity of 92.6%, positive predictive value of 71.4%, and negative predictive value of 100%). The false-positive findings were related to the 2 NIFTPs that share similarities with thyroid cancer. CONCLUSIONS: Our preliminary results suggest to perform a dual-time-point PET/CT acquisition protocol in pHPT patients with uncharacterized centimeter thyroid nodules. However, the real impact of these promising results should be assessed by prospective studies on a larger cohort of patients.

Metabolic Response to BRAF-MEK Combination Therapy in Cecal Neuroendocrine Carcinoma With BRAFV600E Mutation and Refractory Lactic Acidosis.

We report the results of serial F-FDG PET/CT investigations in a 49-year-old woman presenting with an advanced cecal high-grade neuroendocrine carcinoma harboring a somatic BRAF mutation. Patient was refractory to standard chemotherapy regimen showing life-threatening hyperlactatemia. Early after the beginning of BRAF-MEK therapy (dabrafenib and trametinib), impressive improvement in PET/CT imaging was achieved. The pathological F-FDG uptake in cecal primary tumor as well as in nodal, hepatic, and bone metastases drastically decreased. Moreover, the reduction of total lesion glycolysis on PET/CT images was strictly related to extraordinary patient clinical response and lactic acid level normalization.