CONTRAST-ENHANCED ULTRASOUND MONITORING OF PERFUSION CHANGES IN HEPATIC NEUROENDOCRINE METASTASES AFTER SYSTEMIC VERSUS SELECTIVE ARTERIAL 177LU/90Y-DOTATOC AND 213BI-DOTATOC RADIOPEPTIDE THERAPY

Radiopeptide therapy with beta emitter labeled 177Lu/90Y- DOTA(0)-Phe(1)-Tyr(3)-octreotide (DOTATOC) and more recently also alpha emitting 213Bi-DOTATOC are promising new treatments for neuroendocrine tumors. No early predictors for treatment response have been recognized and tumor-shrinkage after radiation therapy appears slowly. In some solid tumors a decline in tumor perfusion was found predictive of final treatment response but the gold standard multiphase computed tomography (CT) has a high radiation burden. Therefore we evaluated the ability of contrast-enhanced ultrasound (CEUS) to evaluate tumor perfusion as a response criteria. Materials and Methods: 14 patients with hepatic neuroendocrine tumor (NET) metastases were enrolled in the retrospective study. Eleven patients were treated with beta-emitting 177Lu/90Y-DOTATOC, either intravenous (i.v.) (n = 5) or intra-arterial (i.a.) (n = 6) and three patients received alpha-emitting 213Bi-DOTATOC (i.a.). CEUS and contrast-enhanced CT (CE-CT) were performed before and 3 months after treatment. Results: CE-CT and CEUS presented comparable results in the baseline study and in the assessment of perfusion changes due to the different treatment regimes. A therapy related decrease in tumor perfusion is an early predictor of longterm morphologic response. Conclusion: CEUS is a cheap, ubiquitary available and radiation free technique which showed comparable results for perfusion and diameter of liver metastases compared to CE-CT. Intensity reduction in an arterial phase CEUS can be seen as a positive sign indicating long term tumor response to treatment. Therefore CEUS may be considered as an imaging modality for monitoring early treatment after focal alpha and beta targeted therapy.JRC.E.5-Nuclear chemistr

Targeting of activated fibroblasts for imaging and therapy

Tumors form a complex environment consisting of a variety of non-malignant cells. Especially cancer-associated fibroblasts have been shown to have an important role for different aspects of malignant tumors such as migration, metastasis, resistance to chemotherapy and immunosuppression. Therefore, a targeting of these cells may be useful for both imaging and therapy. In this respect, an interesting target is the fibroblast activation protein (FAP) which is expressed in activated fibroblasts, but not in quiescent fibroblasts, giving the opportunity to use this membrane-anchored enzyme as a target for radionuclide-based approaches for diagnosis and treatment of tumors and for the diagnosis of non-malignant disease associated with a remodelling of the extracellular matrix

Static and dynamic 68Ga-FAPI PET/CT for the detection of malignant transformation of intraductal papillary mucinous neoplasia of the pancreas.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) may arise from intraductal papillary-mucinous neoplasms (IPMN) with malignant transformation, but a significant portion of IPMN remains to show benign behavior. Therefore, it is important to differentiate between benign IPMN and IPMN lesions undergoing malignant transformation. However, non-operative differentiation by ultrasound, CT, MRI and carbohydrate antigen 19-9 (CA19-9) is still unsatisfactory. Here, we assessed the clinical feasibility of additional assessment of malignancy by positron emission tomography using 68Gallium-labeled Fibroblast Activation Protein Inhibitors (68Ga-FAPI-PET) in 25 patients with magnetic resonance imaging (MRI) - or computed tomography (CT) - proven cystic pancreatic lesions. Methods: 25 patients with cystic pancreatic lesions who were followed up in the European Pancreas Center of Heidelberg University hospital and who were led to surgical resection or fine needle aspiration (FNA) due to suspicious clinical, laboratory chemistry or radiological findings were examined by static (all patients) and dynamic (20 patients) 68Ga-FAPI-PET. Cystic pancreatic lesions were delineated and maximum and mean standardized uptake values (SUVmax / SUVmean) were determined. Time activity curves and dynamic parameters (time to peak, K1, k2, K3, k4) were extracted from dynamic PET data. Receiver operating curves (ROC) of static and dynamic PET parameters were calculated. Results: 11 of the patients suffered from menacing IPMN (high grade IPMN with (6 cases) or without (5 cases) progression into PDAC) and 11 from low grade IPMN, 3 patients from other benign entities. Menacing IMPN showed significantly elevated 68Ga-FAPI uptake compared to low grade IPMN and other benign cystic lesions. In dynamic imaging, menacing IPMN showed increasing time activity curves (TAC) followed by slow decrease afterwards, TAC of low grade IPMN showed an immediate peak followed by rapid decrease for about 10 minutes and slower decrease for the rest of the time. ROC curves showed high sensitivity and specificity (area under the curve (AUC) greater than 80%) of static and dynamic PET parameters for the differentiation of IPMN subtypes. Conclusion: 68Ga-FAPI-PET is a helpful new tool for the differentiation of menacing and low grade IPMN and shows the potential to avoid unnecessary surgery for non-malignant pancreatic IPMN

Simultaneous computed tomography-guided biopsy and radiofrequency ablation of solitary pulmonary malignancy in high-risk patients

Background: In recent years experience has been accumulated in percutaneous radiofrequency ablation (RFA) of lung malignancies in nonsurgical patients. Objectives: In this study, we retrospectively evaluated a simultaneous diagnostic and therapeutic approach including CT-guided biopsy followed immediately by RFA of solitary malignant pulmonary lesions. Methods: CT-guided transthoracic core needle biopsy of solitary pulmonary lesions suspicious for malignancy was performed and histology was proven based on immediate frozen sections. RFA probes were placed into the pulmonary tumors under CT guidance and the ablation was performed subsequently. The procedure-related morbidity was analyzed. Follow-up included a CT scan and pulmonary function parameters. Results: A total of 33 CT-guided biopsies and subsequent RFA within a single procedure were performed. Morbidity of CT-guided biopsy included pulmonary hemorrhage (24%) and a mild pneumothorax (12%) without need for further interventions. The RFA procedure was not aggravated by the previous biopsy. The rate of pneumothorax requiring chest tube following RFA was 21%. Local tumor control was achieved in 77% with a median follow-up of 12 months. The morbidity of the CT-guided biopsy had no statistical impact on the local recurrence rate. Conclusions: The simultaneous diagnostic and therapeutic approach including CT-guided biopsy followed immediately by RFA of solitary malignant pulmonary lesions is a safe procedure. The potential of this combined approach is to avoid unnecessary therapies and to perform adequate therapies based on histology. Taking the local control rate into account, this approach should only be performed in those patients who are unable to undergo or who refuse surgery. Copyright (C) 2012 S. Karger AG, Base

Integration of CT urography improves diagnostic confidence of 68Ga-PSMA-11 PET/CT in prostate cancer patients

Background: To prove the feasibility of integrating CT urography (CTU) into 68Ga-PSMA-11 PET/CT and to analyze the impact of CTU on assigning focal tracer accumulation in the ureteric space to either ureteric excretion or metastatic disease concerning topographic attribution and diagnostic confidence. Methods: Ten prostate cancer patients who underwent 68Ga-PSMA-11 PET/CT including CTU because of biochemical relapse or known metastatic disease were retrospectively analyzed. CTU consisted of an excretory phase 10 min after injection of 80 mL iodinated contrast material. Ureter opacification at CTU was evaluated using the following score: 0, 0% opacification; 1, < 50%; 2, 50–99%; 3, 100%. Topographic attribution and confidence of topographic attribution of focal tracer accumulation in the ureteric space were separately assessed for 68Ga-PSMA-11 PET/CT without and with CTU. Diagnostic confidence was evaluated using the following score: 0, < 25% confidence; 1, 26–50%; 2, 51–75%; 3, 76–100%. Results: At CTU, mean ureter opacification score was 2.6 ± 0.7. At 68Ga-PSMA-11 PET/CT without CTU, mean confidence of topographic attribution of focal tracer accumulation was 2.5 ± 0.7 in total and 2.6 ± 0.7 for metastatic disease. At 68Ga-PSMA-11 PET/CT with CTU, mean confidence of topographic attribution of focal areas of tracer accumulation was significantly higher with 2.9 ± 0.2 in total and 2.7 ± 0.9 for metastatic disease (p < 0.001). In 4 of 34 findings (12%) attribution to either ureteric excretion or metastatic disease was discrepant between 68Ga-PSMA-11 PET/CT without and with CTU (n.s). Conclusions: Integration of CTU into 68Ga-PSMA-11 PET/CT is feasible and increases diagnostic confidence of assigning focal areas of tracer accumulation in the ureteric space to either metastatic disease or ureteric excretion

Semi-automatic 3D-volumetry of liver metastases from neuroendocrine tumors to improve combination therapy with 177Lu-DOTATOC and 90Y-DOTATOC

PURPOSEPatients with neuroendocrine tumors (NET) often present with disseminated liver metastases and can be treated with a number of different nuclides or nuclide combinations in peptide receptor radionuclide therapy (PRRT) depending on tumor load and lesion diameter. For quantification of disseminated liver lesions, semi-automatic lesion detection is helpful to determine tumor burden and tumor diameter in a time efficient manner. Here, we aimed to evaluate semi-automated measurement of total metastatic burden for therapy stratification.METHODSNineteen patients with liver metastasized NET underwent contrast-enhanced 1.5 T MRI using gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid. Liver metastases (n=1537) were segmented using Fraunhofer MEVIS Software for three-dimensional (3D) segmentation. All lesions were stratified according to longest 3D diameter >20 mm or ≤20 mm and relative contribution to tumor load was used for therapy stratification.RESULTSMean count of lesions ≤20 mm was 67.5 and mean count of lesions >20 mm was 13.4. However, mean contribution to total tumor volume of lesions ≤20 mm was 24%, while contribution of lesions >20 mm was 76%.CONCLUSIONSemi-automatic lesion analysis provides useful information about lesion distribution in predominantly liver metastasized NET patients prior to PRRT. As conventional manual lesion measurements are laborious, our study shows this new approach is more efficient and less operator-dependent and may prove to be useful in the decision making process selecting the best combination PRRT in each patient

Preclinical Evaluation of Biodistribution and Toxicity of [211At]PSMA-5 in Mice and Primates for the Targeted Alpha Therapy against Prostate Cancer

Watabe T., Kaneda-Nakashima K., Kadonaga Y., et al. Preclinical Evaluation of Biodistribution and Toxicity of [211At]PSMA-5 in Mice and Primates for the Targeted Alpha Therapy against Prostate Cancer. International Journal of Molecular Sciences 25, 5667 (2024); https://doi.org/10.3390/ijms25115667.Astatine (211At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the 211At-labeled prostate-specific membrane antigen (PSMA) compound ([211At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical biodistribution and toxicity studies for the first-in-human clinical trial. [211At]PSMA-5 was administered to both normal male ICR mice (n = 85) and cynomolgus monkeys (n = 2). The mice were divided into four groups for the toxicity study: 5 MBq/kg, 12 MBq/kg, 35 MBq/kg, and vehicle control, with follow-ups at 1 day (n = 10 per group) and 14 days (n = 5 per group). Monkeys were observed 24 h post-administration of [211At]PSMA-5 (9 MBq/kg). Blood tests and histopathological examinations were performed at the end of the observation period. Blood tests in mice indicated no significant myelosuppression or renal dysfunction. However, the monkeys displayed mild leukopenia 24 h post-administration. Despite the high accumulation in the kidneys and thyroid, histological analysis revealed no abnormalities. On day 1, dose-dependent single-cell necrosis/apoptosis was observed in the salivary glands of mice and intestinal tracts of both mice and monkeys. Additionally, tingible body macrophages in the spleen and lymph nodes indicated phagocytosis of apoptotic B lymphocytes. Cortical lymphopenia (2/10) in the thymus and a decrease in the bone marrow cells (9/10) were observed in the 35 MBq/kg group in mice. These changes were transient, with no irreversible toxicity observed in mice 14 days post-administration. This study identified no severe toxicities associated with [211At]PSMA-5, highlighting its potential as a next-generation targeted alpha therapy for prostate cancer. The sustainable production of 211At using a cyclotron supports its applicability for clinical use

Epithelioid granuloma mimicking lung cancer showed intense uptake on [18F]FAPI-74 PET

The version of record of this article, first published in European Journal of Nuclear Medicine and Molecular Imaging, is available online at Publisher’s website: https://doi.org/10.1007/s00259-023-06478-