[¹⁸F]FDG Uptake and Expression of Immunohistochemical Markers Related to Glycolysis, Hypoxia, and Proliferation in Indeterminate Thyroid Nodules

Purpose: The current study explored the association between 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) uptake and the quantitative expression of immunohistochemical markers related to glucose metabolism, hypoxia, and cell proliferation in benign and malignant thyroid nodules of indeterminate cytology. Procedures: Using a case–control design, 24 patients were selected from participants of a randomized controlled multicenter trial (NCT02208544) in which [18F]FDG-PET/CT and thyroid surgery were performed for Bethesda III and IV nodules. Three equally sized groups of [18F]FDG-positive malignant, [18F]FDG-positive benign, and [18F]FDG-negative benign nodules were included. Immunohistochemical staining was performed for glucose transporters (GLUT) 1, 3, and 4; hexokinases (HK) 1 and 2; hypoxia-inducible factor-1 alpha (HIF1α; monocarboxylate transporter 4 (MCT4); carbonic anhydrase IX (CA-IX); vascular endothelial growth factor (VEGF); sodium-iodide symporter (NIS); and Ki-67. Marker expression was scored using an immunoreactive score. Unsupervised cluster analysis was performed. The immunoreactive score was correlated to the maximum and peak standardized uptake values (SUVmax, SUVpeak) and SUVmax ratio (SUVmax of nodule/background SUVmax of contralateral, normal thyroid) of the [18F]FDG-PET/CT using the Spearman’s rank correlation coefficient and compared between the three groups using Kruskal–Wallis tests. Results: The expression of GLUT1, GLUT3, HK2, and MCT4 was strongly positively correlated with the SUVmax, SUVpeak, and SUVmax ratio. The expression of GLUT1 (p = 0.009), HK2 (p = 0.02), MCT4 (p = 0.01), and VEGF (p = 0.007) was statistically significantly different between [18F]FDG-positive benign nodules, [18F]FDG-positive thyroid carcinomas, and [18F]FDG-negative benign nodules. In both [18F]FDG-positive benign nodules and [18F]FDG-positive thyroid carcinomas, the expression of GLUT1, HK2, and MCT4 was increased as compared to [18F]FDG-negative benign nodules. VEGF expression was higher in [18F]FDG-positive thyroid carcinomas as compared to [18F]FDG-negative and [18F]FDG-positive benign nodules. Conclusions: Our results suggest that [18F]FDG-positive benign thyroid nodules undergo changes in protein expression similar to those in thyroid carcinomas. To expand the understanding of the metabolic changes in benign and malignant thyroid nodules, further research is required, including correlation with underlying genetic alterations.</p

Extraperitoneal leakage as a possible explanation for failure of one-time intraperitoneal treatment in ovarian cancer.

Contains fulltext : 51784.pdf (publisher's version ) (Open Access)We conducted a single-arm study to determine the biodistribution of intraperitoneally (i.p.) administered 90yttrium-labeled murine monoclonal antibody HMFG1 (90Y-muHMFG1) in patients with advanced stage ovarian cancer. Seventeen (17) patients in complete clinical remission for epithelial ovarian cancer were included. After completion of chemotherapy, a mixture of 111indium-labeled muHMFG1 (imaging) and 90Y-muHMFG1 (therapy) was i.p. administered by a surgically placed, indwelling i.p. catheter. Planar and single-photon emission computed tomography images were recorded to determine the distribution of the study medication during the first 6 days postinjection. Of the first 3 patients, 2 patients had extraperitoneal leakage of up to 50% of the injected dose within 24 hours after injection of the study medication. Extraperitoneal leakage was mainly seen in the retroperitoneal spaces covering the upper and lower quadrant of the abdomen. After adjustments in the procedure, leakage was observed in 2 of the remaining 14 patients. Extraperitoneal leakage of i.p. administered therapy does occur. Such leakage would reduce the locally delivered dose of a drug and could potentially have a negative impact on therapeutic efficacy. Given the potential attraction of developing i.p. treatments for intra-abdominal cancer, the observations in this study need to be taken into consideration

Predictive and prognostic value of FDG-PET

The predictive and prognostic value of fluorodeoxyglucose (FDG)-positron emission tomography (PET) in non-small-cell lung carcinoma, colorectal carcinoma and lymphoma is discussed. The degree of FDG uptake is of prognostic value at initial presentation, after induction treatment prior to resection and in the case of relapse of non-small cell lung cancer (NSCLC). In locally advanced and advanced stages of NSCLC, FDG-PET has been shown to be predictive for clinical outcome at an early stage of treatment. In colorectal carcinoma, limited studies are available on the prognostic value of FDG-PET, however, the technique appears to have great potential in monitoring the success of local ablative therapies soon after intervention and in the prediction and evaluation of response to radiotherapy, systemic therapy, and combinations thereof. The prognostic value of end-of treatment FDG-PET for FDG-avid lymphomas has been established, and the next step is to define how to use this information to optimize patient outcome. In Hodgkin's lymphoma, FDG-PET has a high negative predictive value, however, histological confirmation of positive findings should be sought where possible. For non-Hodgkin's lymphoma, the opposite applies. The newly published standardized guidelines for interpretation formulates specific criteria for visual interpretation and for defining PET positivity in the liver, spleen, lung, bone marrow and small residual lesions. The introduction of these guidelines should reduce variability among studies. Interim PET offers a reliable method for early prediction of long-term remission, however it should only be performed in prospective randomized controlled trials. Many of the diagnostic and management questions considered in this review are relevant to other tumour types. Further research in this field is of great importance, since it may lead to a change in the therapeutic concept of cancer. The preliminary findings call for systematic inclusion of FDG-PET in therapeutic trials to adequately position FDG-PET in treatment time lines

Multi-modality nuclear medicine imaging: artefacts, pitfalls and recommendations

Multi-modality imaging is rapidly becoming an essential tool in oncology. Clinically, the best example of multimodality imaging is seen in the rapid evolution of hybrid positron emission tomography (PET)/computed tomography (CT) and single positron emission computed tomography (SPECT)/CT scanners. However, use of multi-modality imaging is prone to artefacts and pitfalls. Important artefacts that may lead to clinical misinterpretation result from the use of CT data to correct for attenuation and the existence of mismatches between the fused images, for example due to respiratory movement. Furthermore, for institutions who proceed from a standalone PET to a hybrid PET-CT, there is an issue of interchangeability between these systems, especially for quantitative studies. Another issue is visualisation: hospital PACS is not sufficiently capable of adequately viewing integrated images. This article reviews and illustrates the most common artefacts and pitfalls that can be encountered in multi-modality nuclear medicine imaging. For correct management of oncological patients it is essential to be able to detect and correctly interpret these artefacts and pitfalls. Therefore, solutions and recommendations to these problems are provided

Hyperthermia and fibrinolytic therapy do not improve the beneficial effect of radioimmunotherapy following cytoreductive surgery in rats with peritoneal carcinomatosis of colorectal origin.

Contains fulltext : 69926.pdf (publisher's version ) (Open Access)BACKGROUND AND OBJECTIVE: Cytoreductive surgery (CS) and heated intraperitoneal chemotherapy (HIPEC) are standard treatment for peritoneal carcinomatosis (PC) of colorectal cancer. Previously, we demonstrated that preclinical radioimmunotherapy (RIT) adjuvant to surgery in PC is a good alternative for HIPEC. Now we aimed to improve the effectiveness of RIT by combining it with whole-body hyperthermia (WBH) or fibrinolytic therapy. METHODS: Rats were inoculated intraperitoneally with colon carcinoma cells. Animals underwent CS, CS + WBH (40 degrees C, 3 hours), CS + RIT (74 MBq 177Lu-labeled MG1), or CS + WBH + RIT. In the second experiment, rats underwent CS, CS + RIT, CS + recombinant tissue plasminogen activator (rtPA, twice daily, 3 days), or CS + RIT + rtPA. RESULTS: Median survival after CS and CS + WBH was 34 and 37 days. Median survival after CS + RIT or CS + RIT + WBH was 63 and 86 days (p < 0.0003, p < 0.0006 compared to CS + WBH). Median survival after CS and CS + rtPA was 50 and 42 days (p = 0.1). Median survival was 106 days after CS + RIT and 103 days after CS + RIT + rtPA (p < 0.0001 compared to CS + rtPA). No difference was found between CS + RIT and CS + RIT + rtPA (p = 0.83). CONCLUSIONS: The application of WBH or rtPA in combination with adjuvant RIT after CS for the treatment of PC of colonic was feasible but did not significantly potentiate the efficacy of RIT

In reaction to: Thuillier P, Benisvy D, Ansquer C, Corvilain B, Mirallie E, Taieb D, et al. Section 5: What is the role of functional imaging and isotopic treatment? Ann Endocrinol (Paris) 2022;83:401-6. https://doi.org/10.1016/j.ando.2022.10.008

Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.RST/Radiation, Science and Technolog

Optimizing Lutetium 177–Anti–Carbonic Anhydrase IX Radioimmunotherapy in an Intraperitoneal Clear Cell Renal Cell Carcinoma Xenograft Model

A new approach in the treatment of clear cell renal carcinoma (ccRCC) is radioimmunotherapy (RIT) using anti-carbonic anhydrase IX (CAIX) antibody G250. To investigate the potential of RIT with lutetium 177 (177Lu)-labeled G250, we conducted a protein dose escalation study and subsequently an RIT study in mice with intraperitoneally growing ccRCC lesions. Mice with intraperitoneal xenografts were injected with 1, 3, 10, 30, or 100 μg of G250 labeled with 10 MBq indium 111 (111In) to determine the optimal protein dose. The optimal protein dose determined with imaging and biodistribution studies was used in a subsequent RIT experiment in three groups of 10 mice with intraperitoneal SK-RC-52 tumors. One group received 13 MBq 177LU-DOTA-G250, a control group received 13 MBq nonspecific 177LU-MOPC21, and the second control group was not treated and received 20 MBq 111In-DOTA-G250. The optimal G250 protein dose to target ccRCC in this model was 10 μg G250. Treatment with 13 MBq 177LU-DOTA-G250 was well tolerated and resulted in significantly prolonged median survival (139 days) compared to controls (49-53 days, p = .015), indicating that RIT has potential in this metastatic ccRCC model