Cancer with unknown primary: finding a needle in a hay stack

Detection and resection of small neuroendocrine tumours (NET) is like finding a needle in a hay stack. Use of specific tracers such as 68Ga-DOTATOC in a PET/CT study has been proven to have a high sensitivity and specificity to cells expressing somatostatin-SSR receptors. The use of 99mTc-Octreotide to detect neuroendocrine tumours during surgery is an effective adjunct for therapy. We here present a clinical case of patient with NET where these modalities help in both diagnostic and therapeutic surgery

Contrast-enhanced ultrasound monitoring of perfusion changes in hepatic neuroendocrine metastases after systemic versus selective arterial ¹⁷⁷Lu/⁹⁰Y-DOTATOC and ²¹³Bi-DOTATOC radiopeptide therapy

Aim - 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. 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. 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 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. Key Words: contrast-enhanced ultrasound, radionuclide therapy, treatment response, DOTATOC PET/CT

Image fusion using CT, MRI and PET for treatment planning, navigation and follow up in percutaneous RFA

Aim: To evaluate the feasibility of fusion of morphologic and functional imaging modalities to facilitate treatment planning, probe placement, probe re-positioning, and early detection of residual disease following radiofrequency ablation (RFA) of cancer. Methods: Multi-modality datasets were separately acquired that included functional (FDG-PET and DCE-MRI) and standard morphologic studies (CT and MRI). Different combinations of imaging modalities were registered and fused prior to, during, and following percutaneous image-guided tumor ablation with radiofrequency. Different algorithms and visualization tools were evaluated for both intra-modality and inter-modality image registration using the software MIPAV (Medical Image Processing, Analysis and Visualization). Semi-automated and automated registration algorithms were used on astandard PC workstation: 1) landmark-based least-squares rigid registration, 2) landmark-based thin-plate spline elastic registration, and 3) automatic voxel-similarity, affine registration. Results: Intra- and inter-modality image fusion were successfully performed prior to, during and after RFA procedures. Fusion of morphologic and functional images provided a useful view of the spatial relationship of lesion structure and functional significance. Fused axial images and segmented three-dimensional surface models were used for treatment planning and post-RFA evaluation, to assess potential for optimizing needle placement during procedures. Conclusion: Fusion of morphologic and functional images is feasible before, during and after radiofrequency ablation of tumors in abdominal organs. For routine use, the semi-automated registration algorithms may be most practical. Image fusion may facilitate interventional procedures like RFA and should be further evaluated

Head-to-head intra-individual comparison of [Ga-68]-FAPI and [F-18]-FDG PET/CT in patients with bladder cancer

DATA AVAILABILITY : The data used and/or analyzed during the current study are available from the corresponding author on reasonable request.Please read abstract in the article.Open Access funding enabled and organized by Projekt DEAL.https://link.springer.com/journal/11307hj2023Nuclear Medicin

[(68) Ga]Ga-FAPI uptake correlates with the state of chronic kidney disease

Purpose Kidney fibrosis leads to a progressive reduction in kidney function ultimately resulting in kidney failure. Diagnostic tools to detect kidney fibrosis are all invasive in nature requiring kidney biopsies with subsequent histological validation. In this retrospective study, the diagnostic value of three different radiotracers for the noninvasive prediction of kidney fibrosis was analyzed, taking into account the glomerular filtration rate (GFR) and the intra-renal parenchymal radiotracer uptake. Methods In 81 patients receiving either one of the following molecular imaging probes, [(68) Ga]Ga-FAPI, [(68) Ga]Ga-PSMA, or [(68) Ga]Ga-DOTATOC, kidney function parameters were correlated with SUVmax and SUVmean of the renal parenchyma and background activity measured in lung parenchyma, myocardium, gluteal muscle, and the abdominal aorta. Patients were clustered according to their grade of chronic kidney disease (CKD), and a regression analysis and one-way ANOVA were conducted in this retrospective analysis. Results We found a negative correlation between GFR and [(68) Ga]Ga-FAPI uptake for both SUVmax and SUVmean values, whereas background activity showed no correlation with GFR. [(68) Ga]Ga-DOTATOC and [(68) Ga]Ga-PSMA did not correlate between CKD stage and intra-renal parenchymal radiotracer uptake. Only [(68) Ga]Ga-PSMA background activity exhibited a positive correlation with GFR suggesting an unspecific binding/retention potentially due to longer circulation times. Conclusion There is a significant negative correlation between renal parenchymal [(68) Ga]Ga-FAPI uptake and GFR, which was not the case for [(68) Ga]Ga-DOTATOC and [(68) Ga]Ga-PSMA. This correlation suggests a specific binding of FAPI rather than a potential unspecific retention in the renal parenchyma, underlining the potential value of [(68) Ga]Ga-FAPI for the noninvasive quantitative evaluation of kidney fibrosis

[(68) Ga]Ga-FAPI uptake correlates with the state of chronic kidney disease

PURPOSE: Kidney fibrosis leads to a progressive reduction in kidney function ultimately resulting in kidney failure. Diagnostic tools to detect kidney fibrosis are all invasive in nature requiring kidney biopsies with subsequent histological validation. In this retrospective study, the diagnostic value of three different radiotracers for the noninvasive prediction of kidney fibrosis was analyzed, taking into account the glomerular filtration rate (GFR) and the intra-renal parenchymal radiotracer uptake. METHODS: In 81 patients receiving either one of the following molecular imaging probes, [(68) Ga]Ga-FAPI, [(68) Ga]Ga-PSMA, or [(68) Ga]Ga-DOTATOC, kidney function parameters were correlated with SUVmax and SUVmean of the renal parenchyma and background activity measured in lung parenchyma, myocardium, gluteal muscle, and the abdominal aorta. Patients were clustered according to their grade of chronic kidney disease (CKD), and a regression analysis and one-way ANOVA were conducted in this retrospective analysis. RESULTS: We found a negative correlation between GFR and [(68) Ga]Ga-FAPI uptake for both SUVmax and SUVmean values, whereas background activity showed no correlation with GFR. [(68) Ga]Ga-DOTATOC and [(68) Ga]Ga-PSMA did not correlate between CKD stage and intra-renal parenchymal radiotracer uptake. Only [(68) Ga]Ga-PSMA background activity exhibited a positive correlation with GFR suggesting an unspecific binding/retention potentially due to longer circulation times. CONCLUSION: There is a significant negative correlation between renal parenchymal [(68) Ga]Ga-FAPI uptake and GFR, which was not the case for [(68) Ga]Ga-DOTATOC and [(68) Ga]Ga-PSMA. This correlation suggests a specific binding of FAPI rather than a potential unspecific retention in the renal parenchyma, underlining the potential value of [(68) Ga]Ga-FAPI for the noninvasive quantitative evaluation of kidney fibrosis

Comparison of neuroendocrine tumor detection and characterization using DOTATOC-PET in correlation with contrast enhanced CT and delayed contrast enhanced MRI

Purpose: We evaluated the rate of successful characterization of gastroenteropancreatic neuroendocrine tumors (NETs) present with an increased somatostatin receptor, comparing CE-CT with CE-MRI, each in correlation with DOTATOC-PET. Methods and materials: 8 patients with GEP-NET were imaged using CE-MRI (Gd-EOB-DTPA), CE-CT (Imeron 400) and DOTATOC-PET. Contrast-enhancement of normal liver-tissue and metastasis was quantified with ROI-technique. Tumor delineation was assessed with visual-score in blind-read-analysis by two experienced radiologists. Results: Out of 40 liver metastases in patients with NETs, all were detected by CE-MRI and the lesion extent could be adequately assessed, whereas CT failed to detect 20% of all metastases. The blind-read-score of CT in arterial and portal phase was median -0.65 and -1.4, respectively, and 2.7 for delayed-MRI. The quantitative ROI-analysis presented an improved contrast-enhancement-ratio with a median of 1.2, 1.6 and 3.3 for CE-CT arterial, portal-phase and delayed-MRI respectively. Conclusion: Late CE-MRI was superior to CE-CT in providing additionally morphologic characterization and exact lesion extension of hepatic metastases from neuroendocrine tumor detected with DOTATOC-PET. Therefore, late enhanced Gd-EOB-DTPA-MRI seems to be the adequate imaging modality for combination with DOTATOC-PET to provide complementary (macroscopic and molecular) tumor characterization in hepatic metastasized NETs

Neurodegenerative changes in Alzheimer's disease: A comparative study of manual, semi-automated and fully automated assessment using MRI

Objective quantification of disease specific neurodegenerative changes can facilitate diagnosis and therapeutic monitoring in several neuropsychiatrie disorders. Reproducibility and easy-to-perform assessment are essential to ensure applicability in clinical environments. Aim of this comparative study is the evaluation of a fully automated approach that assesses atrophic changes in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). 21 healthy volunteers (mean age 66.2), 21 patients with MCI (66.6), and 10 patients with AD (65.1) were enrolled. Subjects underwent extensive neuropsychological testing and MRI was conducted on a 1.5 Tesla clinical scanner. Atrophic changes were measured automatically by a series of image processing steps including state of the art brain mapping techniques. Results were compared with two reference approaches: a manual segmentation of the hippocampal formation and a semi-automated estimation of temporal horn volume, which is based upon interactive selection of two to six landmarks in the ventricular system. All approaches separated controls and AD patients significantly (10-5 < p < 10-4) and showed a slight but not significant increase of neurodegeneration for subjects with MCI compared to volunteers. The automated approach correlated significantly with the manual (r = -0.65, p < 10 -6) and semi automated (r = -0.83, p < 10-13) measurements. It proved high accuracy and at the same time maximized observer independency, time reduction and thus usefulness for clinical routine

First intraindividual comparison of contrast-enhanced MRI, FET- and DOTATOC- PET in patients with intracranial meningiomas.

Background: For irradiation treatment planning of meningiomas the use of PET-scans is well established. The most frequently used tracers are either based on amino acids or the somatostatin receptor ligand DOTATOC. Since up to now no inter-institutionally accepted standard PET-tracer has been defined, the aim of this study was to evaluate the influence of these different types of PET-tracers on the GTV-definition. Methods: Twenty-one patients suffering from intracranial meningiomas underwent CT, MRI, FET- and DOTATOC-PET. First, tumour extension was delineated after image-fusion of CT and MRI (GTV CT/MRI ). Then distinct GTVs based either on FET- or DOTATOC-PET were contoured and compared with each other as well with GTV CT/MRI . Results: Every tumour showed typical enhancement of DOTATOC, but two meningiomas remained FET-negative. The mean relative overlap volume of GTV FET and GTV DOTATOC was only 41.9% and there was a significantly stronger correlation between GTV CT/MRI and GTV DOTATOC than between GTV CT/MRI and GTV FET . Conclusions: Further investigations are necessary to clarify the minor conformity of DOTATOC- and FET-PET in meningiomas. Because of the receptor targeting, DOTATOC is known to be more specific for meningiomas and will remain the standard in our institution with the known limitation in areas nearby the pituitary gland