Despite advances in diagnosis and the use of different therapeutic regimens in astrocytic high-grade glioma (HGG), the prognosis for patients remains grim. Additional pretherapeutic information is needed to tailor management. To gain additional prognostic information at primary diagnosis, we investigated the value ofWe retrospectively evaluated 121 patients who had a primary diagnosis of astrocytic HGG (51 World Health Organization [WHO] grade III; 70 WHO IV) and underwent dynamic 18 F-FET PET before histopathologic assessment. We assessed static parameters (maximal and mean tumoral standardized uptake value corrected for mean background activity in the contralateral hemisphere [SUV max / BG and SUV mean /BG, respectively], biologic tumor volume) and dynamic time-activity curves, including minimal time to peak (TTP min ). The prognostic influence of PET parameters and other clinical parameters on progression-free and overall survival was evaluated using uni-and multivariate Cox regression and Kaplan-Meier survival estimates. Results: In the group overall, median progression-free survival and overall survival were 12.2 and 21.9 mo. SUV max /BG, SUV mean /BG, and biologic tumor volume were significantly higher in WHO IV than in WHO III gliomas; median TTP min was 12.5 min in both groups. On univariate analysis, the factors age, WHO grade, O6-methylguanine-DNA methyltransferase promoter methylation status, contrast enhancement, initial treatment, and TTP min showed prognostic significance, with WHO grade, O6-methylguanine-DNA methyltransferase status, age, and TTP min remaining significant in the multivariate analysis. WHO grade and TTP min reached a similar fit for the prognostic evaluation. The prognosis of WHO III astrocytoma with an early TTP min of 12.5 min or less did not differ significantly from that of glioblastoma. Conclusion: Early TTP min is associated with worse outcome in patients with newly diagnosed astrocytic HGG. In the preoperative setting, TTP min can be a valuable noninvasive prognostic marker with comparable significance to WHO grade. Additionally, TTP min can help identify highly aggressive WHO III astrocytoma tumors and may help in adjusting standard treatment toward an individualized, risk-adapted therapy regime.

TAT. Newly diagnosed grade 1/2 xerostomia after TAT was observed in 5 patients. One patient reported no xerostomia at all. Conclusion:Our first clinical data for TAT using 225 Ac-PSMA-I&T showed promising antitumor effect in advanced mCRPC. These results are highly comparable to data on 225 Ac-PSMA-617 TAT.

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This study analyzed the predictive value of 99m Tc-labeled macroaggregated albumin ( 99m Tc-MAA) SPECT for 90 Y-labeled resin microsphere therapy (radioembolization) by comparing uptake on pretherapeutic 99m Tc-MAA SPECT with uptake on posttherapeutic 90 Y-bremsstrahlung SPECT. Methods: We included 502 patients (55% male; mean age ± SD, 62 ± 11 y) who underwent radioembolization between 2005 and 2013 because of primary or secondary liver malignancies (colorectal cancer [n 5 195, 38 Y-bremsstrahlung scans were used to quantify mean counts per pixel and evaluate the mean tumor-to-background ratio (TBR). Data were given as mean ± SD. Additionally, uptake in lesions on 99m Tc-MAA and 90 Y-bremsstrahlung scans was graded visually as homogeneously higher than (grade 1), heterogeneously higher than (grade 2), equal to (grade 3), or lower than (grade 4) uptake in normal liver tissue. The Mann-Whitney U test and Spearman correlation were used to evaluate statistically significant differences between 99m Tc-MAA and 90 Y-bremsstrahlung SPECT. Results: In total, 1,008 lesions were analyzed. Of the 23% (230/ 1,008) of lesions that had grade 1 uptake on 99m Tc-MAA SPECT, 81% (186/230) remained grade 1 after radioembolization whereas 16% (37/230) were grade 2. Of the lesions with grade 2 uptake on 99m Tc-MAA SPECT, 16% had grade 1 uptake and 82% grade 2 uptake after radioembolization. Of the lesions with grade 3 uptake, however, 27% had grade 1 uptake and 47% grade 2 uptake after radioembolization. Even among the lesions with grade 4 uptake on 99m Tc-MAA SPECT, 21% had grade 1 uptake and 46% grade 2 uptake after radioembolization. The mean TBR on 99m Tc-MAA and 90 Y-bremsstrahlung SPECT showed a significant, though low, correlation in the total population (r 5 0.26; P , 0.001) and in hepatocellular carcinoma (r 5 0.4; P , 0.001), cholangiocellular carcinoma (r 5 0.3; P , 0.05), breast cancer (r 5 0.3; P , 0.001), colorectal cancer (r 5 0.2; P , 0.001), and neuroendocrine tumors (r 5 0.2; P , 0.01). Conclusion: Although significant for most lesions, the correlation between 99m Tc-MAA and 90 Y-microsphere mean TBR was low. Classifying uptake into 4 grades revealed that lesions with high uptake on 99m Tc-MAA SPECT maintain high uptake within radioembolization. More than 60% of lesions with a pretherapeutically lower uptake than in healthy liver tissue, however, showed high uptake within radioembolization. Patients with low tumor uptake on pretherapeutic 99m Tc-MAA imaging should not be excluded from radioembolization.

Background NETTER-1 trial demonstrated high efficacy and low toxicity of four cycles of Peptide Receptor Radionuclide Therapy (PRRT) in patients with metastasized NET. The present study evaluates the outcome of further PRRT cycles in the so called salvage setting in patients after initial response to four therapy cycles and later progression. Methods Thirty five patients (pat.) (25 male, 10 female, 63 ± 9 years) with progressive, metastasized NET (23 small intestinal, 5 lung, 4 CUP, 1 rectal, 1 gastric and 1 paraganglioma) were included. All patients previously received 4 PRRT cycles with 177 Lu-DOTATATE and showed initial response. SPECT based dosimetry was applied to determine kidney and tumor doses. Therapy response was evaluated using 68 Ga-DOTATATE PET/CT (with high dose CT), CT alone or MRI (RECIST 1.1), toxicity was defined using CTCAE 5.0 criteria. 99m Tc99-MAG3 scintigraphy was used to assess potential renal tubular damage. Progression free survival (PFS) and Overall survival (OS) analysis was performed with the Kaplan-Meier-method. Results The median PFS after initial PRRT was 33 months (95% CI: 30–36). The mean cumulative dose for including salvage PRRT was 44 GBq (range 33.5–47). One pat. (2.9%) showed grade 3 hematotoxicity. Kidney dosimetry revealed a mean cumulative kidney dose after a median of 6 PRRT cycles of 23.8 Gy. No grade 3 / 4 nephrotoxicity or relevant decrease in renal function was observed. Follow-up imaging was available in 32 patients after salvage therapy. Best response according to RECIST 1.1. was PR in one patient (3.1%), SD in 26 patients (81.3%) and PD in 5 patients (15.6%). PFS after salvage therapy was 6 months (95% CI: 0–16; 8 patients censored). Mean OS after initial PRRT was 105 months (95% CI: 92–119) and 51 months (95% CI: 41–61) after start of salvage therapy. Median OS was not reached within a follow-up of 71 months after initial PRRT and 25 months after start of salvage PRRT, respectively. Conclusions Salvage therapy with 177 Lu-DOTATATE is safe and effective even in patients with extensive previous multimodal therapies during disease progression and represents a feasible and valuable therapy option for progressive NET. Electronic supplementary material The online version of this article (10.1186/s12885-019-6000-y) contains supplementary material, which is available to authorized users.

The present study evaluated safety, efficacy, and prognostic factors for 90 Y-yttrium microsphere radioembolization of unresectable liver metastases from breast cancer. Methods: Eighty-one patients were treated with radioembolization. Acute toxicity was monitored through daily physical examination and serum tests until 3 d after radioembolization; late toxicity was evaluated until 12 wk after radioembolization. Overall survival and response according to 18 F-FDG PET (.30% decrease of tracer uptake) and CA15-3 serum level (any decline) were recorded. Pretherapeutic characteristics, including pretreatment history, liver function tests, and PET/CT parameters, were assessed by univariate and subsequent multivariate Cox regression for predicting patient survival. Results: A toxicity grade of 3 or more based on clinical symptoms, bilirubin, ulcer, pancreatitis, ascites, or radioembolization-induced liver disease occurred in 10% or less of patients. Two patients eventually died from radioembolization-induced liver disease. Sequential lobar treatment and absence of prior angiosuppressive therapy were both associated with a lower rate of serious adverse events. On the basis of PET/CA15-3 criteria, 52/61% of patients responded to treatment. Median overall survival after radioembolization was 35 wk (interquartile range, 41 wk). Pretherapeutic tumor burden of the liver greater than 50% or more (P , 0.001; hazard ratio, 5.67; 95% confidence interval, 2.41-13.34) and a transaminase toxicity grade of 2 or more (P 5 0.009; hazard ratio, 2.15; 95% confidence interval, 1.21-3.80) independently predicted short survival. Conclusion: Radioembolization for breast cancer liver metastases shows encouraging local response rates with low incidence of serious adverse events, especially in those patients with sequential lobar treatment or without prior angiosuppressive therapy. High hepatic tumor burden and liver transaminase levels at baseline indicate poor outcome.

Although protein-based PET imaging agents are projected to become important tracer molecules in the future, the labeling of complex biomolecules with PET radionuclides is inexpedient and, most of the time, challenging. Methods: Here we present a straightforward labeling chemistry to attach the versatile radionuclide 68 Ga to proteins. Introducing the 68 Ga chelating agent NODA-GA-T (2,29-(7-(1-carboxy-4-(2-mercaptoethylamino)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid) by reaction with proteins chemically processed with sulfo-SMCC (4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt) results in labeling precursors, enabling a simple and rapid kit-labeling procedure that requires no workup of the radiolabeled proteins. Various 68 Ga-proteins were labeled using this method, and the radiochemical yields and specific activities of the labeled proteins were determined. To show that the radiotracers are applicable for in vivo studies, proof-of-concept small-animal PET images were acquired in healthy rats using 68 Ga rat serum albumin for blood-pool imaging and 68 Ga-annexin V for apoptosis imaging in mice with a left ventricular myocardial infarction. Results: The proteins could be modified, yielding 1.2-1.7 68 Ga-labeling sites per protein molecule. All investigated proteins could be labeled in high radiochemical yields of 95% or more in less than 10 min in 1 step, using acetate-buffered medium (pH 3.5-4.0) at room temperature without any further purification. The labeled proteins displayed specific activities of 20-45 GBq/mmol (540-1,200 Ci/mmol). In the proof-of-concept in vivo studies, 68 Ga rat serum albumin and 68 Ga-annexin V were successfully used for in vivo imaging. Both radiotracers showed a favorable biodistribution in the animal models, thus demonstrating the usefulness of the developed approach for the kit 68 Ga labeling of proteins. Conclusion: The preprocessing of proteins proceeds in high chemical yields and with high protein recovery rates after purification. These precursors can be stored for several months at 220°C without degradation, and 68 Ga labeling can be performed in a 1-step kit-labeling reaction in high radiochemical yields. Two of the derivatized model proteins were successfully used in proof-ofconcept in vivo imaging studies to prove the applicability of this kit 68 Ga-labeling technique.

Early TBRmax assessment (5-15 min p.i.) is more accurate for the differentiation between LGG and HGG than the standard static scan (20-40 min p.i.) mainly caused by the characteristic high (18)F-FET uptake of HGG in the initial phase. Therefore, when dynamic (18)F-FET-PET cannot be performed, early TBRmax assessment can be considered as an alternative for tumour grading.