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In radioembolic therapy (RET) of hepatic malignancies using yttrium-90 (Y)-labeled resin microspheres, radiation protection is primarily concerned with avoiding contamination by radioactive spheres. However, as Y is bound to the microsphere surface by a potentially reversible ion-exchange process, the aim of this study was to assess the extent of the potential excreted activity in urine. After RET with Y-labeled resin-based microspheres, urinary excretion of free Y was prospectively analyzed in 51 interventions (n = 45 patients) by sampling urine over 48 h (two 24-h intervals) consecutively. The measured urinary concentration of Y, normalized to the administered microsphere activity, was a median of 58.5 kBq L GBq (range = 3.5-590.9 kBq L GBq) and 17.8 kBq L GBq (1.8-58.8 kBq L GBq) for the first and second 24-h periods after administration, respectively (p ≤ 0.0001, F = 28.4, result from ANOVA). The total excreted activity significantly decreased (p ≤ 0.0001) from a median of 72.5 kBq in the first 24-h period to a median of 22.1 kBq in the second 24-h period. Urinary excretion of free Y after resin-based RET occurs for a longer period and at a higher activity excretion than previously published, which has to be considered when patients are either hospitalized or return home after RET. Existing approaches for patient hospitalization, especially in temporary radiation protection areas, justified by the previously reported lower excretion rate, should be re-evaluated, and as a consequence, the current product safety information and handling recommendations for Y-labeled resin-based microspheres may need to be revised.

Neurotensin receptor-1 (NTR1) is a promising target for diagnostic imaging and targeted radionuclide therapy. The aim of this study was to evaluate the biodistribution profiles of a series of newly developed diarylpyrazole-based NTR1 antagonists regarding their suitability as diagnostic and potentially radiotherapeutic agents. Methods: 3BP-227, 3BP-228, and 3BP-483 were labeled with 111In and injected intravenously into NTR1-positive HT29 xenograft–bearing nude mice. At 3, 6, 12, and 24 h after administration, SPECT/CT images were acquired or mice were sacrificed for ex vivo determination of tissue-associated radioactivity. Results: High-contrast tumor visualization in SPECT/CT images was achieved using the 3 compounds of this study. Ex vivo biodistribution studies confirmed a high and persistent tumor uptake, peaking at 6 h after injection for 111In-3BP-227 (8.4 ± 3.1 percentage injected dose per gram [%ID/g]) and at 3 h after injection for 111In-3BP-228 (10.2 ± 5.3 %ID/g) and 111In-3BP-483 (1.9 ± 0.8 %ID/g). Tumor–to–normal-tissue ratios obtained with 111In-3BP-227 and 111In-3BP-228 were consistently greater than 1. Conclusion: On the basis of the superior biodistribution profile compared with previously reported radiolabeled NTR1 ligands, 111In-3BP-227 is an ideal candidate for further development as a theranostic tracer.

Perfusion scintigraphy using 99mTc-labeled albumin aggregates is mandatory before hepatic radioembolization with 90Y-microspheres. As part of a prospective trial, the intrahepatic and intrapulmonary stability of 2 albumin compounds, 99mTc-MAA (macroaggregated serum albumin [MAA]) and 99mTc-HSA (human serum albumin [HSA]), was assessed. Methods: In 24 patients with metastatic colorectal cancer, biodistribution (liver, lung) and liver–lung shunt (LLS) of both tracers (12 patients each) were assessed by sequential planar scintigraphy (1, 5, and 24 h after injection). Results: Liver uptake of both albumin compounds decreased differently. Although initial LLSs at 1 h after injection were similar in both groups, MAA-LLS increased significantly from 1 (3.9%) to 5 h (7.7%) and 24 h (9.9%) after injection, respectively. HSA-LLS did not change significantly (1 to 5 h), indicating a steady state of pulmonary and intrahepatic degradation. Conclusion: Compared with 99mTc-MAA-microspheres, 99mTc-HSA-microspheres are likely more resistant to degradation over time, allowing a reliable LLS determination even at later time points.

Zusammenfassung Die intraarterielle Selektive Interne Radiotherapie (SIRT) mit 90 Y-markierten Mikrospharen ist mittlerweile eine wichtige lokal-ablative Therapieoption fur die Behandlung onkologischer Patienten geworden. Die SIRT stellt gegenwartig einen palliativen Therapieansatz fur die Behandlung von Lebermalignomen dar. Infolge der Art des 90 Y-Zerfalls als β - -Strahler ohne eine begleitende Gammaemission, bedarf es zur Validierung der erzielten Verteilung des Radioembolisates einer Bremsstrahlungsbildgebung. Dieser Artikel demonstriert durch eine Phantommessung diese Art der Bildgebung und zeigt anhand einer Patientenstudie die Vorteile einer posttherapeutischen Schnittbildgebung. Es werden Ansatzpunkte fur weitere Optimierungen der Bremsstrahlungsbildgebung aufgezeigt.

This study was conducted to investigate the capacity of (99m)Tc-labeled 1-thio-β-D-glucose ((99m)Tc-1-TG) and 5-thio-D-glucose ((99m)Tc-5-TG) to act as a marker for glucose metabolism in tumor cells in vitro.We investigated the cellular uptake of (99m)Tc-1-TG, (99m)Tc-5-TG, and 2-deoxy-2-[(18)F]fluoro-D-glucose((18)F-FDG) in a human colorectal carcinoma and human lung adenocarcinoma cell line (HCT-116, A549) at different time points and varying glucose/insulin concentrations and under transporter blockage by cytochalasin-B and phloretin. Cell compartment analysis was performed.A significant uptake and time dependency thereof, a significant uptake dependency on glucose and insulin and a significant uptake inhibition by cytochalasin-B for (99m)Tc-1-TG and (99m)Tc-5-TG, was shown. Albeit substantial, the uptake was less pronounced in (99m)Tc-1-TG and (99m)Tc-5-TG compared with (18)F-FDG. (99m)Tc-1-TG and (99m)Tc-5-TG showed a higher accumulation in the cell membranes compared with (18)F-FDG.Tc-1-TG and (99m)Tc-5-TG showed an uptake in vitro with glucose analog characteristics but with membranous accumulation. Tumor imaging should be investigated in an animal model.

BACKGROUND: Activated platelets can be found on the surface of inflamed, rupture-prone and ruptured plaques as well as in intravascular thrombosis. They are key players in thrombosis and atherosclerosis. In this study we describe the construction of a radiolabeled single-chain antibody targeting the LIBS-epitope of activated platelets to selectively depict platelet activation and wall-adherent non-occlusive thrombosis in a mouse model with nuclear imaging using in vitro and ex vivo autoradiography as well as small animal SPECT-CT for in vivo analysis. METHODOLOGY/PRINCIPAL FINDINGS: LIBS as well as an unspecific control single-chain antibody were labeled with (111)Indium ((111)In) via bifunctional DTPA ( = (111)In-LIBS/(111)In-control). Autoradiography after incubation with (111)In-LIBS on activated platelets in vitro (mean 3866 ± 28 DLU/mm(2), 4010 ± 630 DLU/mm(2) and 4520 ± 293 DLU/mm(2)) produced a significantly higher ligand uptake compared to (111)In-control (2101 ± 76 DLU/mm(2), 1181 ± 96 DLU/mm(2) and 1866 ± 246 DLU/mm(2)) indicating a specific binding to activated platelets; P

During the last years angiographic Selective Internal Radiotherapy (SIRT) with (90)Y-labelled microspheres has become a common technique for the local-ablative treatment of cancer patients. SIRT is a palliative therapy concept for the treatment of liver malignancies. As a result of (90)Y-decay as β(-)-emitter without a concomitant gamma radiation, Bremsstrahlung imaging is needed to validate the distribution achieved by radioembolisation. This article demonstrates the method of imaging through phantom measurement and shows the advantages of post-therapeutic tomography by means of a patient study. Approaches for further optimization of Bremsstrahlung imaging are discussed.

Ziele: Evaluierung des Uptakes von Tc99m markierten Glucosemolekulen, 1-Thio-β-D-Glucose (1-TG) und 5-Thio-β-D-Glucose (5-TG), in den Tumorzelllinien HCT-116 und A549. Methode: Kultivierung der humanen Karzinomzelllinien HCT-116 (kolorektales-Ca.) und A549 (Adeno-Ca. der Lunge) unter Standardbedingungen. 12h vor Versuch Umsetzen auf glucosefreie Medien. Inkubation von je 1 Mio. Zellen mit 1 MBq F-18-FDG, 1-TG und 5-TG unter verschiedenen Glucose- (0; 2,5; 5 und 10mmol/l) und Insulinkonzentrationen (0,5; 1 und 2 IE/ml mit 5mmol/l Glucose) zu 3 definierten Inkubationszeiten (0,5; 2 und 4h). Zudem Bestimmung des Traceruptakes nach Blockierung der Glucosetransporter GLUT 1–12 mit Cytochalasin B (5, 10 and 20µmol/l) unter glucosefreien Bedingungen. Waschen der Zellen und Messung des Uptakes im Bohrloch. Ergebnis: Es zeigte sich ein maximaler Uptake von 1- und 5-TG nach 4h. Der Uptake betrug maximal 100,4% (1-TG, HCT-116), bzw. 67,4% (5-TG, HCT-116) vom Uptake von F-18-FDG unter glucosefreien Bedingungen. Mit zunehmender Inkubationszeit zeigte sich ein Anstieg des Uptakes, maximal um 492,7% fur F-18-FDG (A549), um 420,5% fur 1-TG (HCT-116) und um 294,2% fur 5-TG (HCT-116) unter glucose- und insulinfreien Bedingungen. Unter glucosefreien Bedingungen konnte der hochste Uptake fur alle Tracer beobachtet werden. Unter Glucosezusatz (10mmol/l) zeigte sich die maximale Reduktion des Uptakes um 95,9% bei F-18-FDG (A549), 41,6% bei 1-TG (HCT-116) und 39,1% bei 5-TG (A549). Insulinzusatz bewirkte eine Zunahme des Uptakes um maximal 135,8% bei F-18-FDG, 17,4% bei 1-TG und 18,7% bei 5-TG (alle HCT-116). Bei Blockade mittels Cytochalasin B Reduktion des Uptakes um 34,8% bei 1-TG (HCT-116) und 38,1% bei 5-TG (A 549). Schlussfolgerung: 1- und 5-TG zeigen einen Uptake in A549 und HCT-116 Zellen. Die Aufnahme ist im Gegensatz zum FDG allerdings geringer ausgepragt. Es zeigen sich Hinweise auf eine glucosetransporterabhangige Aufnahme. Ein Nutzen in der Tumorbildgebung muss in vivo uberpruft werden. Korrespondierender Autor: Seidensticker M Universitatsklinikum Magdeburg, Klinik fur Radiologie und Nuklearmedizin, Leipziger Str. 44, 39120 Magdeburg E-Mail: max.seidensticker@med.ovgu.de

Ziele: MRT basierte volumetrische Evaluation der Effektivitat der „Selective Internal Radiation Therapy“ (SIRT) bei Patienten mit therapierefraktarer progredienter Lebermetastasierung bei kolorektalem Karzinom. Methode: In einer prospektiven Studie wurden 4 Patienten konsekutiv untersucht. Alle Patienten hatten eine chirurgisch nicht resektable, ausgedehnte hepatische Metastasierung. Die Behandlungsoptionen mit Chemotherapeutika und monoklonalen Antikorpern waren ausgeschopft. Vor der Behandlung mit der SIRT und 3 Monate nach der SIRT wurde eine MRT-Untersuchung an einem 1,5 Tesla Gerat mit leberspezifischem Kontrastmittel (Primovist®) durchgefuhrt. Angiographisch wurden pratherapeutisch die extrahepatischen Gefasaste der A. hepatica communis (A. gastroduodenalis, A. cystica und aberrante Gefasaste des Pankreas) embolisiert um eine Verschleppung der Partikel zu verhindern und nach intraarterieller Injektion von Tc-99m-MAA (160 MBq +/- 20) das Ausmas der intrahepatalen Shunts bestimmt. Anschliesend erfolgte die Applikation der Yttrium-90 markierten biokompatiblen Mikrospharen (1,6 GBq +/- 0,2) uber die A. hepatica communis. Die Volumina der Lebermetastasen wurden an einer Bildnachverarbeitungsworkstation manuell bestimmt. Die pra- und posttherapeutischen Volumina wurden miteinander verglichen. Ergebnis: Samtliche Patienten zeigten in den posttherapeutisch durchgefuhrten MRT-Kontrollen nach 3 Monaten eine Volumenreduktion der Lebermetastasen von insgesamt ca. 23% (19%-26%). Schlussfolgerung: Die SIRT ist eine sinnvolle Therapieoption bei hepatisch metastasiertem kolorektalem Karzinom. Korrespondierender Autor: Seemann MD Universitat Magdeburg, Radiologie und Nuklearmedizin, Leipziger Strasse 44, 39120 Magdeburg E-Mail: marcus.seemann@medizin.uni-magdeburg.de

Radioiodine uptake (RIU) is one of the main prognostic factors for curative results of radioiodine therapy in patients with differentiated thyroid cancer. Some days after application of (131)I, the uptake of a subsequent administration of radioiodine was found to be reduced. In contrast, early after irradiation with high-energy photons glucose and amino acid uptake were observed to be increased. Effects of external irradiation on RIU of thyrocytes using high-energy photons have not been investigated so far.Two different cell lines (FRTL-5 and ML-1 cells) derived from thyroid tissue were studied in vitro. Cell lines were either incubated with (131)I only (controls) or additionally irradiated with single doses of 6 or 10 Gy of high-energy photons using a linear accelerator. Cell number and RIU were determined 24-96 h after (131)I application. RIU measurements were repeated after application of sodium perchlorate in excess to investigate specificity of the uptake. Statistical analyses were performed using non-parametric tests.Incubation with radioiodine as well as irradiation with high-energy photons slowed down proliferation in investigated cell lines significantly. Irradiation with solely (131)I resulted in stable or slightly decreased iodide uptake. Compared to those cells, the RIU increased significantly in externally irradiated cells, i. e., additional irradiation with 10 Gy resulted in an almost threefold increase of RIU in FRTL-5 after 72 h. The increase of RIU after irradiation was dose-dependent in both cell lines and could be blocked by perchlorate excess.It could be demonstrated that external irradiation increases RIU in thyroid cell cultures early after irradiation. The increase was dose-dependent and specific, as it could be blocked by perchlorate. This effect appears to be similar to the increase of other actively transported substances after irradiation with high-energy photons. Therefore, the results of this study may contribute to the knowledge of a generalized irradiation-induced mechanism which causes the activation of different cellular transporters. The clinical impact of these findings on combined therapy concepts has to be investigated in further experiments.