US-guided percutaneous ablation of thyroid nodules with 177LU-MAA (LUTMA) - Feasibility study.

PURPOSE: The main purpose is to evaluate the safety, and efficacy of 177Lutetium labeled macroaggregated albumin (LUTMA) ablation of thyroid nodules. MATERIALS AND METHODS: Patients with confirmed benign nodules who were not candidate or did not accept surgery were enrolled. Under ultrasonography (USG) guidance, LUTMA which was produced in our department, was administered into the nodules. Nodule volumes were assessed via USG before the injection and at 1-week, 1-month, and 3-months post-treatment. We calculated the volume reduction rates (VRRs) for these intervals. To detect extranodular activity leakage, patients underwent SPECT/CT imaging at one hour, 24 h, and one week post-injection. RESULTS: Fifteen patients (male: 12, female: 3) with benign thyroid nodules were eligible to join this study. These nodules were categorized as cystic (n = 9), solid (n = 3), or mixed (n = 3). Median nodules volume was 6.59 ml (range: 0.56-55 ml). Predicted absorbed dosee to the nodules varied between 10-1036 Gy. The VRRs at 3 months was 85% for all nodule types with gradual increases over time: 0%-92%, 20%-97%, and 28%-98% at 1 week, 1 month, and 3-months, respectively. The median VRR of cystic nodules was 89% (range: 81%-98%) at 3-months. It is significantly higher than solid ones (P = .009). None of the patients experienced adverse reactions or discomfort during the injection or follow-up. CONCLUSION: LUTMA treatment significantly reduces the volume of benign thyroid nodules, offering relief from disease-associated symptoms and cosmetic concerns. It emerges as a promising alternative to surgical and other local treatments for benign thyroid nodule ablation. CLINICAL SIGNIFICATION: LUTMA is a novel theranostic radiopharmaceutical which is promising in local ablative treatment of benign thyroid nodules.

Leukocyte Labeling with Tc-99m-HMPAO: The Role of Leucocyte Numbers and Medication on the Labeling Efficacy and Image Quality.

Objectives: The aim of this study is to evaluation of Tc-99m-hexamethylpropyleneamineoxime (HMPAO)-labeled leukocytes in terms of radiochemical, biochemical, and microbiological quality controls and to examine the effect of leukocyte numbers of the blood obtained from patients and the medications currently used by the patients on the radiochemical yields of Tc-99m-HMPAO-labeled leukocytes, and imaging quality was evaluated. Methods: Thirty paients were included in our study who applied to Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Department of Nuclear Medicine for Tc-99m-HMPAO-labeled leukocyte scintigraphy. Devices and chemicals used in the preparation of Tc-99m-HMPAO-labeled laukocytes were compared with other nuclear medicine clinics. Tc-99m-HMPAO-labeled leukocytes were evaluated in terms of radiochemical, biochemical, and microbiological quality controls. The effect of leukocyte numbers of the blood obtained from patients and the medications currently used by the patients on the radiochemical yields of Tc-99m-HMPAO-labeled leukocytes and imaging quality was evaluated. Results: The pH range of Tc-99m-HMPAO was 6-8 and the radiochemical purity was 90±2.04% (n=30), the radiochemical yield of Tc-99m-HMPAO-labeled leukocytes was 51±2.18% (n=30), the radiolabeling yield of Tc-99m-HMPAO-labeled leukocyte increased as the amount of white blood cell in the blood increased and whether the patients used any antibiotic, blood thinners, insulin and blood pressure medications did not affect the radiolabeling yield of Tc-99m-HMPAO-labeled leukocytes. The number of erythrocytes were removed at a rate of >99% in LPR by starch solution (6% HES; in the hemocytometric examination of Tc-99m-HMPAO-labeled leukocytes performed zeroth and 4th h, living/dead cell ratio was found 97.5% and the product was sterile. Conclusion: Tc-99m-HMPAO was labeled with leukocytes successfully, and Tc-99m-HMPAO-labeled leukocytes was safely injected to the patients as sterile without loss of vitality and aggregation.

Evaluation of F-18 DOPA PET/CT in the detection of recurrent or metastatic medullary thyroid carcinoma: comparison with GA-68 DOTA-TATE PET/CT.

OBJECTIVE: PET imaging with F-18 DOPA (FDOPA) and Ga-68 DOTATATE (TATE) shows the most promising results to detect medullary thyroid cancer (MTC) recurrence. We performed this comparative study to detect the site of recurrent or metastatic disease in MTC patients with elevated serum calcitonin (Ctn) and/or carcinoembryonic antigen (CEA) levels. METHODS: We studied 46 MTC patients (25 women, 21 men) with elevated Ctn and/or CEA levels during follow-up who had both FDOPA and TATE PET/CT scans for re-staging purposes. RESULTS: FDOPA PET imaging yielded an overall sensitivity of 86.8%, specificity of 100%, PPV of 100%, NPV of 61.5%, and accuracy of 89.1%, while TATE PET scan had the same values as 84.2%, 87.5%, 96.9%, 53.8%, and 84.6%, respectively, and there was no statistically significant difference between the two modalities with the exception of the specificity value that was higher for FDOPA imaging. In a subgroup of patients with overt Ctn or CEA elevation, sensitivity of FDOPA increased significantly, whereas TATE sensitivity did not change. FDOPA PET imaging was significantly superior in detecting liver and regional lymph node (LN) metastases, while TATE PET scan was significantly better in the skeletal metastases. Early FDOPA demonstrated 11 invisible lesions on late FDOPA. CONCLUSION: Both FDOPA and TATE PET/CT imaging are useful to localize recurrences in MTC patients. While TATE imaging is superior to reveal skeletal disease, FDOPA seems better in liver and regional LN metastases; therefore, the two modalities appear complementary in monitoring MTC patients with elevated serum Ctn and/or CEA levels.

Small Molecule, Multimodal, [18F]-PET and Fluorescence Imaging Agent Targeting Prostate-Specific Membrane Antigen: First-in-Human Study.

BACKGROUND: A first-in-human study of [18F]-BF3-Cy3-ACUPA, a small-molecule imaging agent that can be unimolecularly both positron emitting and fluorescent, is conducted to determine its safety, biodistribution, radiation dosimetry, feasibility in tumor detection by preoperative positron emission tomography (PET), as well as its intraoperative fluorescence imaging utility in patients with prostate-specific membrane antigen positive (PSMA+) tumors. METHODS: Ten patients aged 66 ± 7 years received a 6.5 ± 3.2 mCi intravenous injection of [18F]-BF3-Cy3-ACUPA and underwent PET/computed tomography (CT) imaging. Radiation dosimetry of [18F]-BF3-Cy3-ACUPA, normal organ biodistribution, and tumor uptakes were examined. Two patients were prescheduled for radical prostatectomy (RP) with extended pelvic lymphadenectomy approximately 24 hours following [18F]-BF3-Cy3-ACUPA injection and imaging. Without reinjection, intraoperative fluorescence imaging was performed on freshly excised tissue during RP. Frozen sections of excised tissue during RP were submitted for confirmatory histopathology and multiphoton fluorescence and brightfield microscopy. RESULTS: Absorbed doses by organs including the kidneys and salivary glands were similar to 68Ga-PSMA-11 imaging. [18F]-BF3-Cy3-ACUPA physiologic radiotracer accumulation and urinary/biliary excretion closely resembled the distribution of other published PSMA tracers including [18F]-JK-PSMA-7, [18F]-PSMA-1007, [18F]-DCFPyL, and [18F]-DCFBC. 19F-BF3-Cy3-ACUPA was retained in PSMA+ cancer tissues in patients for at least 24 hours, allowing for intraoperative fluorescence assessment of the prostate and of the embedded prostate cancer without contrast reinjection. After 24 hours, the imaging agent mostly decayed or cleared from the blood pool. Preoperative PET and fluorescence imaging findings were confirmed with final histopathology and multiphoton microscopy. CONCLUSION: Our first-in-human results demonstrate that [18F]-BF3-Cy3-ACUPA is safe and feasible in humans. Larger trials with this PET tracer are expected to further define its capabilities and its clinical role in the management of PSMA+ tumors, especially in prostate cancer.

Performance of F-18 Fluorocholine PET/CT for Detection of Hyperfunctioning Parathyroid Tissue in Patients with Elevated Parathyroid Hormone Levels and Negative or Discrepant Results in conventional Imaging.

OBJECTIVE: Our aim was to assess the diagnostic performance of F-18 fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) in detecting hyperfunctioning parathyroid tissue (HPT) in patients with elevated parathyroid hormone levels with negative or inconclusive conventional imaging results and to compare the findings with those obtained using technetium-99m sestamibi (MIBI) scintigraphy and neck ultrasonography (US). MATERIALS AND METHODS: Images of 105 patients with hyperparathyroidism who underwent FCH PET/CT, dual-phase MIBI parathyroid scintigraphy (median interval: 42 days), and neck US were retrospectively analyzed. The gold standard was histopathological findings for 81 patients who underwent parathyroidectomy and clinical follow-up findings in the remaining 24 patients. Sensitivities, positive predictive values (PPVs), and accuracies were calculated for all imaging modalities. RESULTS: Among the 81 patients who underwent parathyroidectomy, either parathyroid adenoma (n = 64), hyperplasia (n = 9), neoplasia (n = 4), or both parathyroid adenoma and hyperplasia (n = 1) were detected, except 3 patients who did not show HPT. Of the 24 (23%) patients who were followed-up without operation, 22 (92%) showed persistent hyperparathyroidism. FCH PET/CT showed significantly higher sensitivity than MIBI scintigraphy and US in detection of HPT (p < 0.01). Sensitivity, PPV, and accuracy of FCH PET/CT were 94.1% (95/101), 97.9% (95/97), and 92.4% (97/105), respectively. The corresponding values for MIBI scintigraphy and US were 45.1% (46/102), 97.9% (46/47), and 45.7% (48/105) and 44.1% (45/102), 93.8% (45/48), and 42.9% (45/105), respectively. Among the 35 patients showing negative MIBI scintigraphy and neck US findings, 30 (86%) showed positive results on FCH PET/CT. FCH PET/CT could demonstrate ectopic locations of HPT in 11 patients whereas MIBI and US showed positive findings in only 6 and 3 patients, respectively. CONCLUSION: FCH PET/CT is an effective imaging modality for detection of HPT with the highest sensitivity among the available imaging techniques. Therefore, FCH PET/CT can be recommended especially for patients who show negative or inconclusive results on conventional imaging.

177Lu-Labeled Macroaggregated Albumin Imaging and Treatment Effect in Patient with Cystic Thyroid Nodule.

A number of different peptides or antibodies have been labeled with 177Lu and used for clinical imaging and treatment. To our knowledge, 177Lu had never before been used to label macroaggregated albumin, and our radiopharmacy laboratory at Istanbul University-Cerrahpasa made a special effort to do so. We present the case of a 43-y-old man whose cystic thyroid nodule was treated with an intranodular injection of 177Lu-macroaggregated albumin and imaged with SPECT/CT.

Correlation of SUVmax and Apparent Diffusion Coefficient Values Detected by Ga-68 PSMA PET/MRI in Primary Prostate Lesions and Their Significance in Lymph Node Metastasis: Preliminary Results of an On-going Study

Objectives: Gallium-68 (Ga-68) prostate specific membrane antigen (PSMA) positron emission tomography (PET) has been shown to be more accurate than multiparametric prostate magnetic resonance imaging (MRI) in detection of primary prostate lesions. Using hybrid PET/MRI we aim to detect the correlation between SUVmax and apparent diffusion coefficient (ADC) in primary prostate lesions and to assess their prognostic value in detection of lymph node (LN) metastasis. Methods: Twenty-six patients, who were diagnosed as having prostate cancer with biopsy and underwent Ga-68 PSMA PET/MRI together with biparametric prostate MRI (bpMRI) were included. SUVmax, SUVmean and ADC were recorded for index lesions drawing a region of interest (ROI) of 1 cm2 around the pixel with the highest SUVmax (ROI-1) and another ROI following borders of prostate tumor detected by bpMRI (ROI-2). Presence of LN metastasis was recorded according to PSMA PET/MRI Results: SUVmax was inversely correlated with ADC (ROI-1: p=0.010; ROI-2: p=0.017 for b=800). SUVmax and SUVmeans were both higher in patients with LN metastasis and ADC was lower in patients with LN metastasis for ROI-1. SUVmax cut-off value of 19.8 for ROI-1 and 20.9 for ROI-2 had sensitivity and specificity of 77.8% and 76.5%, respectively for detection of LN metastasis, whereas ADC (b=800) cut-off value of 0.92x10-3 mm2/s had sensitivity and specificity of 87.5% and 76.5%, respectively. SUVmax/ADC (b=800) ratio increased the sensitivity and specificity to 100% and 82.4%, respectively. Conclusion: SUV and ADC values are inversely correlated in primary prostate lesions and the combined use of both values increases the diagnostic accuracy of hybrid PET/MRI in the detection of primary prostate lesions.

Comparison of Ga-68 PSMA positron emission tomography/computerized tomography with Tc-99m MDP bone scan in prostate cancer patients

Background/aim: The aim of our study was to compare Tc-99m MDP bone scan and Ga-68 PSMA PET/CT in terms of detection of bone metastasis in prostate cancer patients. Materials and methods: A total of 28 prostate cancer patients with bone scan and PSMA PET/CT performed within 90 days were retrospectively included in our analysis. All bone lesions were scored as negative (score-0), positive (score-1), or suspicious (score-2) for metastasis by two experienced nuclear medicine physicians. Both patient-based and region-based analyses were made for all osseous lesions. Results: On per-patient analysis; sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 72.7%, 52.9%, 50%, 75%, and 60.7%, respectively, for bone scan and 90.9%, 100%, 100%, 94.4%, and 96.4%, respectively, for PSMA PET/CT. On per-region analysis; sensitivity, specificity, PPV, NPV, and accuracy were 76.2%, 80.9%, 57.1%, 91.1%, and 79.8%, respectively, for bone scan and 85.7%, 100%, 100%, 95.5%, and 95.4%, respectively, for PSMA PET/CT. Conclusion: Ga-68 PSMA PET/CT has higher sensitivity, specificity, and accuracy compared to bone scan in terms of bone metastasis detection in prostate cancer patients. Therefore, it might be the modality of choice for patients with suspicion for metastatic disease, despite negative bone scan and conventional imaging results

Lu-177-PSMA-617 Prostate-Specific Membrane Antigen Inhibitor Therapy in Patients with Castration-Resistant Prostate Cancer: Stability, Bio-distribution and Dosimetry.

OBJECTIVE: The aim of the study was to estimate the radiation-absorbed doses and to study the in vivo and in vitro stability as well as pharmacokinetic characteristics of lutetium-177 (Lu-177) prostate-specific membrane antigen (PSMA)-617. METHODS: For this purpose, 7 patients who underwent Lu-177-PSMA therapy were included into the study. The injected Lu-177-PSMA-617 activity ranged from 3.6 to 7.4 GBq with a mean of 5.2±1.8 GBq. The stability of radiotracer in saline was calculated up to 48 h. The stability was also calculated in blood and urine samples. Post-therapeutic dosimetry was performed based on whole body and single photon emission computed tomography/computed tomography (SPECT/CT) scans on dual-headed SPECT/CT system. RESULTS: The radiochemical yield of Lu-177-PSMA-617 was >99%. It remained stable in saline up to 48 h. Analyses of the blood and urine samples showed a single radioactivity peak even at 24 hours after injection. Half-life of the distribution and elimination phases were calculated to be 0.16±0.09 and 10.8±2.5 hours, respectively. The mean excretion rate was 56.5±8.8% ranging from 41.5% to 65.4% at 24 h. Highest radiation estimated doses were calculated for parotid glands and kidneys (1.90±1.19 and 0.82±0.25 Gy/GBq respectively). Radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p<0.05) (0.030±0.008 Gy/GBq). CONCLUSION: Lu-177-PSMA-617 is a highly stable compound both in vitro and in vivo. Lu-177-PSMA-617 therapy seems to be a safe method for the treatment of castration-resistant prostate cancer patients. The fractionation regime that enables the longest duration of tumor control and/or survival will have to be developed in further studies.