The bone marrow (BM) is a main risk organ during Lu-177-PSMA ligand therapy of metastasized castration-resistant prostate cancer (mCRPC) patients. So far, BM dosimetry relies on S values, which are pre-computed for reference anatomies, simplified activity distributions, and a physiological BM distribution. However, mCRPC patients may show a considerable bone lesion load, which leads to a heterogeneous and patient-specific activity accumulation close to BM-bearing sites. Furthermore, the patient-specific BM distribution might be significantly altered in the presence of bone lesions. The aim was to perform BM absorbed dose calculations through Monte Carlo (MC) simulations and to investigate the potential value of image-based BM localization. This study is based on 11 Lu-177-PSMA-617 therapy cycles of 10 patients (10 first cycles), who obtained a pre-therapeutic Ga-68-PSMA-11 PET/CT; quantitative Lu-177 SPECT acquisitions of the abdomen 24 (+CT), 48, and 72 h p.i.; and a Lu-177 whole-body planar acquisition at 24 h post-therapy. Patient-specific 3D volumes of interest were segmented from the Ga-68-PSMA-11 PET/CT, filled with activity information from the Lu-177 data, and imported into the FLUKA MC code together with the patient CT. MC simulations of the BM absorbed dose were performed assuming a physiological BM distribution according to the ICRP 110 reference male (MC1) or a displacement of active BM from the direct location of bone lesions (MC2). Results were compared with those from S values (SMIRD). BM absorbed doses were correlated with the decrease of lymphocytes, total white blood cells, hemoglobin level, and platelets. For two patients, an additional pre-therapeutic Tc-99m-anti-granulocyte antibody SPECT/CT was performed for BM localization. Median BM absorbed doses were 130, 37, and 11 mGy/GBq for MC1, MC2, and SMIRD, respectively. Significant strong correlation with the decrease of platelet counts was found, with highest correlation for MC2 (MC1: r = − 0.63, p = 0.04; MC2: r = − 0.71, p = 0.01; SMIRD: r = − 0.62, p = 0.04). For both investigated patients, BM localization via Tc-99m-anti-granulocyte antibody SPECT/CT indicated a displacement of active BM from the direct location of lesions similar to model MC2 and led to a reduction in the BM absorbed dose of 40 and 41% compared to MC1. Higher BM absorbed doses were observed for MC-based models; however, for MC2, all absorbed doses were still below 2 Gy. MC1 resulted in critical values for some patients, but is suspected to yield strongly exaggerated absorbed doses by neglecting bone marrow displacement. Image-based BM localization might be beneficial, and future studies are recommended to support an improvement for the prediction of hematoxicities.

Background: We performed an initial evaluation of non-invasive ECG-gated [¹⁸ F]FDG-positron emission tomography (FDG-PET) for serial measurements of left ventricular volumes and function in murine models of dilated (DCM) and ischemic cardiomyopathy (ICM), and then tested the effect of erythropoietin (EPO) treatment on DCM mice in a preliminary FDG-PET therapy monitoring study. Methods: Mice developed DCM 8 weeks after injection with Coxsackievirus B3 (CVB3), whereas ICM was induced by ligation of the left anterior descending artery. LV volumes (EDV and ESV) and the ejection fraction (LVEF) of DCM, ICM and healthy control mice were measured by FDG-PET and compared with reference standard results obtained with 1.5 T magnetic resonance imaging (MRI). In the subsequent monitoring study, LVEF of DCM mice was evaluated by FDG-PET at baseline, and after 4 weeks of treatment, with EPO or saline. Results: LV volumes and the LVEF as measured by FDG-PET correlated significantly with the MRI results. These correlations were higher in healthy and DCM mice than in ICM mice, in which LVEF measurements were somewhat compromised by absence of FDG uptake in the area of infarction. LV volumes (EDV and ESV) were systematically underestimated by FDG-PET, with net bias such that LVEF measurements in both models of heart disease exceeded by 15% to 20% results obtained by MRI. In our subsequent monitoring study of DCM mice, we found a significant decrease of LVEF in the EPO group, but not in the saline-treated mice. Moreover, LVEF in the EPO and saline mice significantly correlated with histological scores of fibrosis. Conclusions: LVEF estimated by ECG-gated FDG-PET significantly correlated with the reference standard MRI, most notably in healthy mice and mice with DCM. FDG-PET served for longitudinal monitoring of effects of EPO treatment in DCM mice.

Purpose: There are controversial debates if patients with Hürthle cell carcinoma, also known as oxyphilic or oncocytic cell follicular thyroid carcinoma, have a poorer outcome. In this study, we systematically evaluated the clinical outcome in a large patient cohort following thyroidectomy and initial I-131 radioactive iodine therapy (RIT). Methods: We retrospectively evaluated a total of 378 patients with diagnosed oncocytic follicular Hürthle cell carcinoma (OFTC) (N = 126) or with classical follicular thyroid carcinoma (FTC) (N = 252). Patients received thyroidectomy and complementary I-131 RIT. Clinical data regarding basic demographic characteristics, tumor grade, persistent disease and recurrence during follow-up, and disease-free, disease-specific, and overall survival were collected during follow-up of 6.9 years (interquartile range 3.7; 11.7 years). Univariate and multivariate analyses were used to identify factors associated with disease-related and overall survival. Results: Before and after matching for risk factors, recurrence was significantly more frequently diagnosed in OFTC patients during follow-up (17% vs. 8%; p value 0.037). Likewise, OFTC patients presented with a reduced mean disease-free survival of 17.9 years (95% CI 16.0–19.8) vs. 20.1 years (95% CI 19.0–21.1) in FTC patients (p value 0.027). Multivariate analysis revealed OFTC (HR 0.502; 95% CI 0.309–0.816) as the only independent prognostic factor for disease-free survival. Distant metastases of OFTC patients were significantly less iodine-avid (p value 0.014). Mean disease-specific and overall survival did not differ significantly (p value 0.671 and 0.687) during follow-up of median 6.9 years (3.7; 11.7 years). Conclusions: Our study suggests that recurrence is more often seen in OFTC patients. OFTC patients have a poorer prognosis for disease-free survival. Thus, OFTC and FTC behave differently and should be categorized separately. However, patients suffering from OFTC present with the same overall and disease-specific survival at the end of follow-up indifferent to FTC patients after initial RIT.

Background: [⁶⁸Ga]Ga-FAPI-46 is a novel positron emission tomography (PET) ligand that targets fibroblast activation protein (FAP) expression as FAP inhibitor (FAPI) and could already show promising results in several tumor entities. It could be demonstrated that an increased FAP expression correlates with tumor aggressivity in urothelial carcinoma (UC). Given the limited value of [¹⁸F]FDG in UC, [⁶⁸Ga]Ga-FAPI-46 could add diagnostic information in staging and response assessment in UC. We present the first data of [⁶⁸Ga]Ga-FAPI-46 PET imaging in a pilot cohort of UC patients evaluating uptake characteristics in metastases and primary tumors. Methods: Fifteen patients with UC prior to or after local treatment underwent [⁶⁸Ga]Ga-FAPI-46 PET/CT imaging for detection of metastatic spread. We compared the biodistribution in non-affected organs and tumor uptake of UC lesions by standard uptake value measurements (SUV_mean and SUV_max). Additionally, metastatic sites on PET were compared to its morphological correlate on contrast-enhanced computed tomography (CT). Results: Overall, 64 tumor sites were detected on PET and/or CT. The highest uptake intensity was noted at the primary site (SUV_max 20.8 (range, 8.1–27.8)) followed by lymph node metastases (SUV_max 10.6 (range, 4.7–29.1)). In 4/15 (26.7%) patients there were [⁶⁸Ga]Ga-FAPI-46-positive lesions that were missed on standard routine CT imaging. On the other hand, 2/15 patients had suspicious prominent bipulmonary nodules as well as pelvic lymph nodes previously rated as suspicious for metastatic spread on CT, but without increased FAPI expression; here histopathology excluded malignancy. Conclusion: [⁶⁸Ga]Ga-FAPI-46 PET shows distinctly elevated uptake in UC lesions. Therefore, the tracer has potential as a promising new biomarker in metastatic UC patients, as [⁶⁸Ga]Ga-FAPI-46 PET might improve detection of metastatic sites compared to CT alone. These findings highly emphasize larger studies investigating FAPI imaging in UC patients.

To improve therapy outcome of Yttrium-90 selective internal radiation therapy (90Y SIRT), patient-specific post-therapeutic dosimetry is required. For this purpose, various dosimetric approaches based on different available imaging data have been reported. The aim of this work was to compare post-therapeutic 3D absorbed dose images using Technetium-99m (99mTc) MAA SPECT/CT, Yttrium-90 (90Y) bremsstrahlung (BRS) SPECT/CT, and 90Y PET/CT. Ten SIRTs of nine patients with unresectable hepatocellular carcinoma (HCC) were investigated. The 99mTc SPECT/CT data, obtained from 99mTc-MAA-based treatment simulation prior to 90Y SIRT, were scaled with the administered 90Y therapy activity. 3D absorbed dose images were generated by dose kernel convolution with scaled 99mTc/90Y SPECT/CT, 90Y BRS SPECT/CT, and 90Y PET/CT data of each patient. Absorbed dose estimates in tumor and healthy liver tissue obtained using the two SPECT/CT methods were compared against 90Y PET/CT. The percentage deviation of tumor absorbed dose estimates from 90Y PET/CT values was on average -2 ± 18% for scaled 99mTc/90Y SPECT/CT, whereas estimates from 90Y BRS SPECT/CT differed on average by -50 ± 13%. For healthy liver absorbed dose estimates, all three imaging methods revealed comparable values. The quantification capabilities of the imaging data influence 90Y SIRT tumor dosimetry, while healthy liver absorbed dose values were comparable for all investigated imaging data. When no 90Y PET/CT image data are available, the proposed scaled 99mTc/90Y SPECT/CT dosimetry method was found to be more appropriate for HCC tumor dosimetry than 90Y BRS SPECT/CT based dosimetry.

Trans-arterial radioembolization (TARE) is increasingly evaluated for unresectable intrahepatic cholangiocarcinoma (ICC). Not all ICC patients benefit equally well from TARE. Therefore, we sought to evaluate variables predicting progression-free survival (PFS) and overall survival (OS). Patients with non-resectable ICC underwent TARE and were treated with 90Y resin microspheres. Baseline characteristics, biochemical/clinical toxicities, and response were examined for impact on PFS and OS. A total of 103 treatments were administered to 73 patients without major complications or toxicity. Mean OS was 18.9 months (95% confidence intervals (CI); 13.9–23.9 months). Mean and median PFS were 10.1 months (95% CI; 7.9–12.2) and 6.4 months (95% CI; 5.20–7.61), respectively. Median OS and PFS were significantly prolonged in patients with baseline cholinesterase (CHE) ≥ 4.62 kU/L (OS: 14.0 vs. 5.5 months; PFS: 6.9 vs. 3.2 months; p < 0.001). Patients with a tumor burden ≤ 25% had a significantly longer OS (15.2 vs. 6.6 months; p = 0.036). Median PFS was significantly longer for patients with multiple TARE cycles (24.4 vs. 5.8 months; p = 0.04). TARE is a considerable and safe option for unresectable ICC. CA-19-9, CHE, and tumor burden have predictive value for survival in patients treated with TARE. Multiple TARE treatments might further improve survival; this has to be confirmed by further studies.