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.

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.

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.

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.

The role of PSMA PET/CT imaging in restaging of prostate cancer patients with low prostate-specific antigen levels.

INTRODUCTION: Prostate-specific membrane antigen (PSMA) is increasingly being recognized as a novel target for the PET imaging of prostate cancer (PCa) and Ga-DKFZ-11 (Ga-PSMA) has been suggested as a novel tracer for detection of PCa relapses and metastases. The aim of this study was to evaluate the diagnostic value of PSMA PET/CT in the diagnosis of recurrent PCa with low prostate-specific antigen (PSA) levels. PATIENTS AND METHODS: We carried out a retrospective analysis of patients who underwent PSMA PET/CT from November 2013 to December 2014 in our department. Among these patients, 50 out of 178 who had increasing PSA levels (<5 ng/ml) and did not have known metastasis were included in this study. RESULTS: Patients had an average PSA of 1.41 ng/ml. A total of 29 patients (58%) showed at least one positive lesion. PET positivity rates of 31% (n=4), 54% (n=13), and 88% (n=14) were observed in patients with a PSA level of less than 0.2, 0.2-2, and 2-5 ng/ml, respectively. A positive correlation was observed between positivity rate and Gleason scores and blood PSA levels. Verification was performed in 46 patients, with biopsy (n=3) and follow-up, and conventional imaging studies at the time of the PET/CT or during follow-up with a mean period of 10.6±3.3 months and ranged from 3.8 to 16.4 months. According to patient-based analysis of 46 cases, 57% of patients had true positive, 24% of patients had true negative, 2% of patients had false positive, an 18% of patients had false-negative findings. A sensitivity of 76.47% (95% confidence interval: 58.83-89.25%) and a specificity of 91.67% (95% confidence interval: 61.52-99.79%) were found. CONCLUSION: PET/CT with Ga-PSMA is a valuable tool for assessing recurrence of PCa with a high sensitivity in patients who have PSA levels between 0.2 and 5 ng/ml. In addition, this study suggests that PSMA PET/CT can be used in patients with very low (<0.2 ng/ml) but increasing PSA levels, which, in many cases, may influence further clinical management.

Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer.

PURPOSE: (177)Lu-617-prostate-specific membrane antigen (PSMA) ligand seems to be a promising tracer for radionuclide therapy of progressive prostate cancer. However, there are no published data regarding the radiation dose given to the normal tissues. The aim of the present study was to estimate the pretreatment radiation doses in patients who will undergo radiometabolic therapy using a tracer amount of (177)Lu-labeled PSMA ligand. METHODS: The study included seven patients with progressive prostate cancer with a mean age of 63.9 ± 3.9 years. All patients had prior PSMA positron emission tomography (PET) imaging and had intense tracer uptake at the lesions. The injected (177)Lu-PSMA-617 activity ranged from 185 to 210 MBq with a mean of 192.6 ± 11.0 MBq. To evaluate bone marrow absorbed dose 2-cc blood samples were withdrawn in short variable times (3, 15, 30, 60, and 180 min and 24, 48, and 120 h) after injection. Whole-body images were obtained at 4, 24, 48, and 120 h post-injection (p.i.). The geometric mean of anterior and posterior counts was determined through region of interest (ROI) analysis. Attenuation correction was applied using PSMA PET/CT images. The OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. RESULTS: The calculated radiation-absorbed doses for each organ showed substantial variation. The highest radiation estimated doses were calculated for parotid glands and kidneys. Calculated radiation-absorbed doses per megabecquerel were 1.17 ± 0.31 mGy for parotid glands and 0.88 ± 0.40 mGy for kidneys. The radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p < 0.05). The calculated radiation dose to bone marrow was 0.03 ± 0.01 mGy/MBq. CONCLUSION: Our first results suggested that (177)Lu-PSMA-617 therapy seems to be a safe method. The dose-limiting organ seems to be the parotid glands rather than kidneys and bone marrow. The lesion radiation doses are within acceptable ranges; however, there is a substantial individual variance so patient dosimetry seems to be mandatory.

Evaluation of PSMA PET/CT imaging using a 68Ga-HBED-CC ligand in patients with prostate cancer and the value of early pelvic imaging.

PURPOSE: The aim of the study was to evaluate the diagnostic value of the prostate-specific membrane antigen (PSMA) ligand (68)Ga-HBED-CC (PSMA PET/CT) in patients with prostate cancer and evaluate the value of early imaging of the pelvis. MATERIALS AND METHODS: The files of 28 patients were retrospectively evaluated. All patients had a histopatological confirmation of prostate cancer. PSMA PET/CT images were obtained at 5 and 60 min after injection from all patients. RESULTS: Intense pathologic radiotracer uptake was observed in 23 patients (77%) at the site of primary tumour. Lymph node metastases were detected in 10 patients (36%) and bone metastases were detected in seven patients (25%). Bone scan (n=25) results revealed metastatic bone lesions in four patients, equivocal results in nine patients and normal results in 12 patients. PSMA PET/CT confirmed bone metastases in all four patients. Pathologic radiotracer uptake in PSMA PET/CT scans was observed only in one patient among those who had equivocal bone scans. PSMA PET/CT showed additional bone lesions in two patients who had a normal bone scan. When we compared early and late pelvic images we found no difference in the number of lesions detected. The maximum standardized uptake value (SUV(max)) for primary tumour, lymph nodes and bone metastases was significantly higher in late images. CONCLUSION: PSMA PET/CT imaging seems to be a valuable imaging modality for evaluation of primary prostate cancer and it seems to have potential for the detection of lymph node and bone metastases. Early images 5 min p.i. can help to better distinguish between urinary bladder (before tracer accumulation occurs) and tumour lesions.

Evaluation and comparison of Ga-68 DOTA-TATE and Ga-68 DOTA-NOC PET/CT imaging in well-differentiated thyroid cancer.

BACKGROUND: Somatostatin receptor (Sstr) scintigraphy with radiolabelled somatostatin analogues has been used extensively for the diagnosis and therapy of Sstr-expressing tumours. It has been shown that well-differentiated thyroid cancer (WDTC) cells have a high expression of Sstr2, Sstr3 and Sstr5. Hence, WDTC cells could be an ideal target for the evaluation of lesion uptake of Ga-68 DOTA-1-NaI3-octreotide (DOTA-NOC), which has a high affinity not only to Sstr2 but also to Sstr3 and Sstr5. The aim of the present study was to evaluate the value of Ga-68 DOTA-NOC as a target for Sstr2-expressing, Sstr3-expressing and Sstr5-expressing tumours in WDTC patients and to compare the results with those of Ga-68 DOTA-TATE in the same patient population. METHOD: Thirteen patients with WDTC were included in our study: nine with papillary thyroid cancer, three with Hurthle cell carcinoma and one with follicular thyroid carcinoma. All patients had elevated serum thyroglobulin levels and negative post-therapeutic I-131 whole-body scans, which were obtained after the last radioiodine treatment. All patients had undergone two consecutive PET imaging studies with Ga-68 DOTA-D-Phe1-Tyr3-octreotate (DOTA-TATE) and Ga-68 DOTA-NOC, respectively. All images were evaluated visually, and maximum standardized uptake values were calculated. RESULTS: Both Ga-68 DOTA-TATE and Ga-68 DOTA-NOC PET images gave comparable results. Among the 13 patients, imaging with both Ga-68 DOTA-TATE and Ga-68 DOTA-NOC gave negative results in five (38%) patients and positive results in eight (62%) patients. A total of 45 lesions were identified on Ga-68 DOTA-TATE images and 42 on Ga-68 DOTA-NOC images; three lesions were missed. Lesion uptake was significantly higher on Ga-68 DOTA-TATE images. Maximum standardized uptake values of Ga-68 DOTA-TATE and Ga-68 DOTA-NOC were 12.9±9.1 and 6.3±4.1 (n=54, P<0.001), respectively. CONCLUSION: Our study suggested that Ga-68 DOTA-TATE has a higher lesion uptake even in WDTC patients and may have potential advantage over Ga-68 DOTA-NOC.