Clinical Results of Holmium-166 Radioembolization with Personalized Dosimetry for the Treatment of Hepatocellular Carcinoma.

Transarterial radioembolization (TARE) with 166Ho-loaded microspheres is an established locoregional treatment for hepatocellular carcinoma (HCC), introduced in 2010. This study evaluates the clinical outcome of patients with HCC who underwent 166Ho-TARE with personalized dosimetry. Twenty-seven patients with 36 TARE procedures were analyzed. Treatment planning, execution, and evaluation was possible without complications in all cases. At the 3-month follow-up, disease control in the treated liver was achieved in 81.8% of patients (complete remission, partial remission, and stable disease in 36.4%, 31.8%, and 13.6%, respectively). The median overall survival (OS) was 17.2 months, and progression-free survival (PFS) in the treated liver was 11 months. Statistically significant positive correlations were observed between the achieved radiation dose for the tumor and both PFS (r = 0.62, p < 0.05) and OS (r = 0.48, p < 0.05), suggesting a direct dose-response relationship. The calculated achieved dose was 8.25 Gy lower than the planned dose, with relevant variance between planned and achieved doses in individual cases. These results confirm the efficacy of the 166Ho-TARE holmium platform and underscore the potential of voxel-based, personalized dosimetry to improve clinical outcomes.

Dependence of Renal Uptake on Kidney Function in [68Ga]Ga-PSMA-11 PET/CT Imaging.

(1) Background: PSMA ligand PET/CT is increasingly important for diagnostics of prostate cancer and other tumor diseases. In particular, the radiopharmaceutical [68Ga]Ga-PSMA-11 is widely used. Besides its tumor-specific binding, the uptake within the kidneys is dominant and seems to visualize the renal cortex specifically. Kidney diseases may alter the uptake of radiopharmaceuticals. Therefore, the correlation between renal uptake in PET/CT imaging and renal function should be investigated. (2) Methods: A group of 103 male patients were retrospectively evaluated for eGFR according to the CKD-EPI equation, tracer uptake intensity (SUVmax, SUVpeak, SUVmean), the molecular volume of the renal cortex, morphological kidney size, and total renal uptake. Manual and three different computer-assisted contouring methods (thresholds at 50% of SUVmax, 30% of SUVmax, and absolute SUV of 20) were used for measurements. Correlations between parameters were calculated using linear regression models. (3) Results: Renal SUVmax, SUVpeak, and SUVmean do not correlate with eGFR for manual or computer-assisted measurements. In contrast, molecular cortex volume shows a moderate correlation with eGFR (R2 = 0.231, p < 0.001), superior to morphological kidney size. A contouring threshold of 30% of SUVmax outperformed the other settings for renal cortex volume and total renal uptake. (4) Conclusions: Renal uptake of [68Ga]Ga-PSMA-11 cannot predict eGFR, but the functional renal cortex can be quantified by PET/CT imaging.

Transarterial Radioembolization (TARE) in Patients with Hepatocellular Carcinoma: A Comparison of Palliative with Bridging-to-Transplant Concepts.

We investigated transarterial radioembolization (TARE) as a palliative measure and bridging-to-transplant therapy in hepatocellular carcinoma (HCC) patients. A total of 167 patients (50 bridging, 117 palliative) with 245 TARE procedures were assessed. Fourteen patients underwent subsequent liver transplantation (LT). Patients undergoing LT exhibited significantly prolonged progression-free survival (PFS) compared to those with bridging-without-transplant (p = 0.033). No significant differences were observed between patients with bridging-without-transplant and palliative cases (p = 0.116). Median overall survival (OS) post-TARE was 16.6 months, with estimated OS rates at 6/12 months of 82.0%/60.5%, respectively. Patients who underwent LT demonstrated statistically significantly longer OS compared to those with bridging-without-transplant (p = 0.001). No marked outcome distinctions were found between bridging-without-transplant and palliative groups. The findings underscored the superiority of LT over alternative treatments. TARE served as an important component in non-LT scenarios, allowing for subsequent therapeutic options. The study reflected the highly variable and complex situations of patients with HCC, emphasizing the need for further investigations to define an optimal multimodal approach.

Image-Guided Fine-Needle Aspiration Cytology for BRCA Mutation Assessment of PSMA-Positive Lymph Node Metastases in a Patient With Metastatic Castration-Resistant Prostate Cancer.

ABSTRACT: A 64-year-old man with metastatic castration-resistant prostate cancer presented for prostate-specific membrane antigen (PSMA) PET/CT in preparation for 177 Lu-PSMA radioligand therapy. For precedent BRCA mutation assessment, fine-needle aspiration cytology of 2 PSMA-positive lymph node metastases was conducted. The acquired material was suitable for next-generation sequencing-based gene panel diagnostics and did not show a BRCA1 / 2 mutation, thus PSMA radioligand therapy was initiated. Fine-needle aspiration cytology of lymph node metastases may be a viable option in evaluating further therapeutic alternatives.

Noninvasive Verification of a Very Small Intraocular Prostate Carcinoma Metastasis by 68Ga-PSMA-11 PET/CT.

ABSTRACT: A male patient underwent 68Ga-PSMA-11 PET/CT for the evaluation of a suspected intraocular metastasis in the right eye. Although the choroidal thickening was very small (4 × 2 mm), and ophthalmoscopy as well as MRI were inconclusive, PET/CT imaging showed distinct PSMA expression in the suspected lesion, confirming prostate cancer metastasis. The ability of dedicated PSMA ligand PET/CT imaging to detect small metastases, even with 68Ga-labeled ligands, has been demonstrated. Therefore, the use of further invasive diagnostic procedures could be avoided. Thus, the possibility of detecting intraocular metastases of prostate cancer should be considered in routine PET/CT imaging.

Clinical Results of Transarterial Radioembolization (TARE) with Holmium-166 Microspheres in the Multidisciplinary Oncologic Treatment of Patients with Primary and Secondary Liver Cancer.

Holmium-166 microspheres are used for the transarterial radioembolization (TARE) treatment of primary and secondary liver cancers. In this study, its efficacy regarding local tumor control and integration into the oncological treatment sequence of the first 20 patients treated in our institution were examined. A total of twenty-nine 166Ho-TARE procedures were performed to treat hepatocellular carcinoma (HCC, fourteen patients), metastatic colorectal cancer (mCRC, four patients), intrahepatic cholangiocarcinoma (ICC, one patient), and hemangioendothelioma of the liver (HE, one patient). In eight patients, 166Ho-TARE was the initial oncologic treatment. In patients with HCC, the median treated-liver progression-free survival (PFS), overall PFS, and overall survival after 166Ho-TARE were 10.3, 7.3, and 22.1 months; in patients with mCRC, these were 2.6, 2.9, and 20.6 months, respectively. Survival after 166Ho-TARE in the patients with ICC and HE were 5.2 and 0.8 months, respectively. Two patients with HCC were bridged to liver transplantation, and one patient with mCRC was downstaged to curative surgery. In patients with HCC, a median treatment-free interval of 7.3 months was achieved. In line with previous publications, 166Ho-TARE was a feasible treatment option in patients with liver tumors, with favorable clinical outcomes in the majority of cases. It was able to achieve treatment-free intervals, served as bridging-to-transplant, and did not prevent subsequent therapies.

The effect of butylscopolamine on [18F]FDG uptake in the gastrointestinal tract is negligible and regionally variable.

BACKGROUND: Butylscopolamine (or hyoscine butylbromide, trade name Buscopan®) is occasionally administered as a premedication to reduce non-specific FDG uptake in the gastrointestinal tract based on its antiperistaltic effect. To date, there are no consistent recommendations for its use. The aim of this study was to quantify the reduction in intestinal and non-intestinal uptake by butylscopolamine administration and to derive relevance for clinical evaluation. RESULTS: 458 patients (PET/CT for lung cancer) were retrospectively reviewed. 218 patients with butylscopolamine and 240 patients without butylscopolamine had comparable characteristics. While the SUVmean in the gullet/stomach and small intestine was significantly reduced with butylscopolamine, the colon and rectum/anus showed no difference. The liver and salivary glands showed a reduced SUVmean, while skeletal muscle and blood pool were unaffected. An effect of butylscopolamine was particularly evident in men and patients under 65 years of age. There was no difference in the perceived confidence in the assessment of intestinal findings in the subjective evaluation, although in the butylscopolamine group further diagnostics appeared advisable more frequently. CONCLUSIONS: Butylscopolamine reduces gastrointestinal FDG accumulation only in selected segments and, despite a significant effect, only to a small extent. A general recommendation for the use of butylscopolamine cannot be derived from these results, its use for specific issues could be considered individually.

67 Ga-PSMA I&T for Radioguided Surgery of Lymph Node Metastases in Patients With Biochemical Recurrence of Prostate Cancer.

PURPOSE: Radioguided lymph node dissection in patients with prostate cancer, and suffering from biochemical recurrence has been described thoroughly during the past few years. Several prostate-specific membrane antigen (PSMA)-directed ligands labeled with 111 In, 99m Tc, and 68 Ga have been published; however, limitations regarding availability, short half-life, high costs, and unfavorable high energy might restrict frequent use. This study aims at introducing 67 Ga as a promising radionuclide for radioguided surgery. METHODS: Retrospective analysis was performed on 6 patients with 7 PSMA-positive lymph node metastases. 67 Ga-PSMA I&T (imaging and therapy) was synthesized in-house and intravenously applied according to §13 2b of the German Medicinal Products Act. Radioguided surgery was performed 24 hours after injection of 67 Ga-PSMA I&T using a gamma probe. Patient urine samples were collected. Occupational and waste dosimetry was performed to describe hazards arising from radiation. RESULTS: 67 Ga-PSMA application was tolerated without adverse effects. Five of 7 lymph nodes were detected on 22-hour SPECT/CT in 4 of 6 patients. During surgery, all 7 lymph node metastases were identified by positive gamma probe signal. Relevant accumulation of 67 Ga was observed in lymph node metastases (32.1 ± 15.1 kBq). Histology analysis of near-field lymph node dissection revealed more lymph node metastases than PET/CT (and gamma probe measurements) identified. Waste produced during inpatient stay required decay time of up to 11 days before reaching exemption limits according to German regulations. CONCLUSIONS: Radioguided surgery using 67 Ga-PSMA I&T is a safe and feasible option for patients suffering from biochemical recurrence of prostate cancer. 67 Ga-PSMA I&T was successfully synthesized according to Good Manufacturing Practice guidelines. Radioguided surgery with 67 Ga-PSMA I&T does not lead to relevant radiation burden to urology surgeons and represents a novel interdisciplinary approach in nuclear medicine and urology.

A Novel Breast Cancer Xenograft Model Using the Ostrich Chorioallantoic Membrane-A Proof of Concept.

The avian chorioallantoic membrane (CAM) assay has attracted scientific attention in cancer research as an alternative or complementary method for in vivo animal models. Here, we present a xenograft model based on the ostrich (struthio camelus) CAM assay for the first time. The engraftment of 2 × 106 breast cancer carcinoma MDA-MB-231 cells successfully lead to tumor formation. Tumor growth monitoring was evaluated in eight fertilized eggs after xenotransplantation. Cancer cells were injected directly onto the CAM surface, close to a well-vascularized area. Histological analysis confirmed the epithelial origin of tumors. The CAM of ostrich embryos provides a large experimental surface for the xenograft, while the comparably long developmental period allows for a long experimental window for tumor growth and treatment. These advantages could make the ostrich CAM assay an attractive alternative to the well-established chick embryo model. Additionally, the large size of ostrich embryos compared to mice and rats could help overcome the limitations of small animal models. The suggested ostrich model is promising for future applications, for example, in radiopharmaceutical research, the size of the embryonal organs may compensate for the loss in image resolution caused by physical limitations in small animal positron emission tomography (PET) imaging.

Preparation and labelling of red blood cells with [68Ga]Ga-oxine for PET/CT imaging of the human spleen.

INTRODUCTION: With the introduction of automated synthetization methods, the in-house production of several 68Ga-based tracers became feasible in hospital laboratories. We describe a possible standard operating procedure (SOP) for [68Ga]Ga-oxine-labeled heat-denaturated erythrocytes, which can be used for selective imaging in patients with splenic disorders. METHODS: Heat-denaturated erythrocytes were labeled with [68Ga]Ga-oxine, which was produced from 68Ga and 8-hydroxyquinoline on an automated synthesizer. The workflow was validated in a good manufacturing/good radiopharmaceutical practice (GMP/GRP) certified laboratory. A patient underwent [68Ga]Ga-oxine-erythrocyte PET/CT for differentiation of an intrapancreatic mass. RESULTS: [68Ga]Ga-oxine and [68Ga]Ga-oxine-labeled erythrocytes could be synthesized reproducibly and reliably. The products met GMP quality standards. The tracer showed high accumulation in the intrapancreatic mass, consistent with an accessory spleen. CONCLUSIONS: PET/CT imaging with [68Ga]Ga-oxine-labeled, heat-denaturated erythrocytes can be a backup method for the differentiation of functioning splenic tissue from tumors. An SOP for the production of the tracer in a clinical setting could be established.

Liver PET Reloaded: Automated Synthesis of [68Ga]Ga-BP-IDA for Positron Imaging of the Hepatobiliary Function and First Clinical Experience.

Hepatobiliary scintigraphy is a well-established nuclear imaging method for evaluating liver function and displaying the biliary system, but the spatial and temporal resolution is limited, and, there is still no established PET equivalent. Adapted from the work of Schuhmacher et al. in 1983, the production of a 68Gallium-labeled substitute, tetrabromophthalein ([68Ga]Ga-BP-IDA), was undertaken according to current Good Manufacturing Practice (GMP) standards and proved feasible and reproducible. PET/CT with the radiotracer was performed in two complex patients with hepatocellular carcinoma in preparation for transarterial radioembolization. Due to its high spatial and temporal resolution, localization of areas with impaired liver function and visualization of the biliary system were possible. We could demonstrate that this 68Gallium-labeled, IDA-based PET tracer is feasible and could advance hepatic and biliary function PET imaging.

PET/CT of the Spleen with Gallium-Oxine-Labeled, Heat-Damaged Red Blood Cells: Clinical Experience and Technical Aspects.

Several scintigraphic techniques have been supplemented or replaced by PET/CT methods because of their superior sensitivity, high resolution, and absolute activity quantification capability. The purpose of this project was the development of a PET tracer for splenic imaging, its radiopharmaceutical validation, and its application in selected patients in whom unclear constellations of findings could not be resolved with established imaging methods. Heat-damaged red blood cells (RBCs) were labeled with [68Ga]gallium-oxine, which was produced from [68Ga]gallium and 8-Hydroxyquinoline (oxine) on an automated synthesizer. Ten patients underwent [68Ga]gallium-oxine-RBC-PET/CT for the classification of eleven unclear lesions (3 intra-, 8 extrapancreatic). [68Ga]gallium-oxine and [68Ga]gallium-oxine-labeled RBCs could be synthesized reproducibly and reliably. The products met GMP quality standards. The tracer showed high accumulation in splenic tissue. Of the 11 lesions evaluated by PET/CT, 3 were correctly classified as non-splenic, 6 as splenic, 1 as equivocal, and 1 lesion as a splenic hypoplasia. All lesions classified as non-splenic were malignant, and all lesions classified as splenic did not show malignant features during follow-up. PET/CT imaging of the spleen with [68Ga]gallium-oxine-labeled, heat-damaged RBCs is feasible and allowed differentiation of splenic from non-splenic tissues, and the diagnosis of splenic anomalies.

Exceptional response to neoadjuvant targeted therapy with the selective RET inhibitor selpercatinib in RET-fusion-associated sarcoma.

With the increasing use of next-generation sequencing, highly effective targeted therapies have been emerging as treatment options for several cancer types. Recurrent gene-fusions have been recognized in sarcomas; however, options for targeted therapy remain scarce. Here, we describe a case of a sarcoma, associated with a RET::TRIM33-fusion gene with an exceptional response to a neoadjuvant therapy with the selective RET inhibitor selpercatinib. Resected tumor revealed subtotal histopathologic response. This is the first report of successful targeted therapy with selpercatinib in RET-fusion-associated sarcomas. As new targeted therapies are under development, similar treatment options may become available for sarcoma patients.

Impact of metabolic indices of 18F-fluorodeoxyglucose positron emission tomography/computed tomography on post transplantation recurrence of hepatocellular carcinoma.

BACKGROUND: Tumor recurrence is the leading cause of death after liver transplantation in patients with hepatocellular carcinoma. There is an ongoing debate as to whether metabolic indices such as tumor to liver standardized uptake value ratio in 18F-fluorodeoxyglucose positron emission tomography/computed tomography of the primary tumor can identify patients outside the Milan criteria with as low recurrence rates as patients inside Milan and thus should be added to the established prognostic factors. METHODS: This retrospective study analyzes 103 consecutive patients who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography before liver transplantation for hepatocellular carcinoma using data of clinical tumor registry. Primary endpoints were overall survival and 10-year cumulative recurrence rates. RESULTS: Tumor to liver standardized uptake value ratio of the primary tumor was statistically significant higher in Milan out tumors, "up-to-seven" out tumors, grade 3 tumors, α- fetoprotein level >400 ng/ml and lesions > 5cm in diameter. Factors with statistically significant influence on the 10- year overall survival in the univariate analysis were Milan, up-to-seven" criteria, number of lesions and pT-category. COX regression analysis did not show independently statistically significant factors for 10-year overall survival. Milan, "up-to-seven" criteria, grade, pV, number of lesions, size of lesion, pT-category, tumor to liver standardized uptake value ratio influenced 10-year cumulative recurrence rates statistically significant. Tumor to liver standardized uptake value ratio, grade and pT-category proved to be independently statistically significant factors for 10-year cumulative recurrence rates. CONCLUSIONS: Our study suggests that tumor to liver standardized uptake value standardized uptake value ratio in 18F-fluorodeoxyglucose positron emission tomography/computed tomography is an independent prognostic factor in transplanted patients with hepatocellular carcinoma. If we focus on preoperative findings, such as tumor size, tumor number and AFP value adding the information given by TLR of 18F-FDG PET/CT allows to estimate the risk of tumor recurrence more accurate than the established classifications Milan and UTS. Therefore, it may add valuable information to other preoperative findings, such as tumor size, tumor number and AFP level.

Warthin-Like Papillary Thyroid Microcarcinoma With Coincidental Ipsilateral Warthin Tumor of the Parotid Gland Detected on 131 I-SPECT/US and 18 F-PET/US Fusion Imaging.

ABSTRACT: A 66-year-old woman was referred with an incidental finding of a bilateral papillary thyroid microcarcinoma after thyroidectomy. On the right side, a Warthin-like variant was observed. After radioiodine therapy, whole-body scan revealed an unclear iodine uptake on the right-sided neck. For further clarification, 131 I-SPECT/US and 18 F-PET/US fusion imaging were performed, unambiguously revealing iodine and glucose uptake within a hypoechoic lesion located in the parenchyma of the right parotid gland. Surgical excision confirmed a Warthin tumor ipsilateral to the Warthin-like variant of the papillary thyroid microcarcinoma. Because the extensive imaging, targeted minimal-invasive surgery was possible.

Excellent Response to Multimodal Therapy Approach in Hyperfunctioning Metastatic Follicular Thyroid Carcinoma Diagnosed on 123 I-SPECT/Ultrasound Fusion Imaging.

ABSTRACT: An 83-year-old woman presented with new-onset hyperthyroidism and suspicious thyroid nodules on ultrasound (US). Conventional 99m TcO 4 thyroid scintigraphy showed hyperfunctioning areas that could not be clearly assigned to the US findings. With the aid of 123 I-SPECT/US fusion imaging, suspicious nodules were unambiguously identified as autonomously hyperfunctioning lesions. Additional 123 I whole-body scan revealed iodine-avid lymphonodular and pulmonal metastases. Clinical diagnosis of hormone-active thyroid carcinoma was made and histologically confirmed. Because of significant hyperthyroidism as well as multiple partially iodine-negative metastases, a multimodal treatment regime consisting of 131 I radioiodine therapy, surgery, and radiation therapy was conducted, leading to almost complete remission.

High-Resolution Splenic Imaging: [68Ga]Ga-Oxine Red Blood Cell PET/CT for Differentiation of Splenosis Mimicking Malignant Lymphoma.

The differentiation of splenic tissue from malignant lesions via imaging may be challenging, particularly considering aberrant or accessory lesions and diseases that are rarely encountered. Functioning splenic tissue can be identified using technetium-99m red blood cell (99mTc-RBC) scintigraphy, but its sensitivity is limited and may not be available. We present the case of a patient in whom disseminated abdomino-pelvic splenosis was diagnosed using PET/CT with gallium-68-oxine-labeled RBCs. The method represents a feasible and probably superior alternative to splenic scintigraphy.

Synchronous Metastatic Medullary Thyroid Carcinoma and Paraesophageal Parathyroid Adenoma Detected on 18 F-Ethylcholine PET/US Fusion Imaging.

ABSTRACT: An 80-year-old woman with osteoporosis without fractures was referred with asymptomatic primary hyperparathyroidism and elevated calcitonin level. Ultrasound, 99m Tc-pertechnetate scintigraphy, 99m Tc-MIBI scintigraphy, and CT revealed a suspicious thyroid nodule and enlarged submandibular lymph nodes. However, no parathyroid adenoma was depictable. 18 F-choline PET/CT showed increased uptake of the proximal esophagus, but neither CT nor US revealed a parathyroid lesion, and only 18 F-choline PET/US fusion imaging confirmed a paraesophageal parathyroid adenoma. Resection of both medullary thyroid carcinoma and ectopic parathyroid adenoma through a single cervicotomy was conducted (thyroidectomy, neck dissection, extirpation of parathyroid adenoma); parathyroid hormone and calcitonin dropped to normal. Multiple endocrine neoplasia IIa syndrome was suspected.

Radiation doses from low-dose CT scans in SPECT/CT and PET/CT examinations: A survey in Germany.

AIM: Recently, dose reference levels (DRLs) have been defined in Germany for auxiliary low-dose CT scans in hybrid SPECT/CT and PET/CT examinations, based on data from 2016/17. Here, another survey from 2020 was evaluated and compared with the new DRLs as well as with similar surveys from foreign countries. METHODS: The survey, which had already been conducted in the Nordic countries, queried for various examinations including the following values: patient weight and height, volume CT dose index (CTDIvol), dose length product (DLP). For each examination, statistical parameters such as the third quartile (Q3) were determined from all submitted CTDIvol and DLP values. Additionally, for examinations comprising datasets from at least 10 systems, the third quartile (Q3-Med) of the respective median values of each system was calculated. Q3 and Q3-Med were compared with the newly published DRLs from Germany and values from similar studies from other countries. RESULTS: Data from 15 SPECT/CT and 13 PET/CT systems from 15 nuclear medicine departments were collected. For the following examinations datasets from more than 10 systems were submitted: SPECT lung VQ, SPECT bone, SPECT&PET cardiac, PET brain, PET oncology. Especially for examinations of the thorax and heart, the new DRLs are very strict compared to this study. The CTDIvol values for examinations of the head were lower in this study than the DRLs prescribe now. CONCLUSIONS: For certain examination types, there is a need for dose optimization at some clinics and devices in order to take into account the new DRLs in Germany in the future.

Multimodal Characterization of a PSMA-Positive Thyroid Nodule Using 68Ga-PSMA and 124Iodine PET/US Fusion Imaging.

A 54-year-old male diagnosed with prostate cancer was referred for 68Gallium-PSMA-11 PET/CT. The scan revealed a solitary PSMA-positive thyroid lesion. On PET/ultrasound fusion imaging, a nodule with moderate risk of malignancy (TIRADS 4B) could be unambiguously correlated. Additional 124Iodine PET/ultrasound fusion imaging revealed normal iodine uptake within the PSMA-positive thyroid nodule. Fine-needle aspiration cytology was performed using an ultrasound needle-guidance system. The cytopathological investigation confirmed a benign thyroid nodule and excluded a thyroid carcinoma as well as a prostate cancer metastasis. Immunohistochemistry was positive for thyroglobulin staining.