Diagnostic Performance of [F]TFB PET/CT Compared with Therapeutic Activity [I]Iodine SPECT/CT and [F]FDG PET/CT in Recurrent Differentiated Thyroid Carcinoma.

[F]tetrafluoroborate ([F]TFB) is an emerging PET tracer with excellent properties for human sodium iodide symporter (NIS)-based imaging in patients with differentiated thyroid cancer (DTC). The aim of this study was to compare [F]TFB PET with high-activity posttherapeutic [I]iodine whole-body scintigraphy and SPECT/CT in recurrent DTC and with [F]FDG PET/CT in suspected dedifferentiation. Twenty-six patients treated with high-activity radioactive [I]iodine therapy (range, 5.

Tumor-Targeted Interleukin 2 Boosts the Anticancer Activity of FAP-Directed Radioligand Therapeutics.

We studied the antitumor efficacy of a combination of Lu-labeled radioligand therapeutics targeting the fibroblast activation protein (FAP) (OncoFAP and BiOncoFAP) with the antibody-cytokine fusion protein L19-interleukin 2 (L19-IL2) providing targeted delivery of interleukin 2 to tumors. The biodistribution of Lu-OncoFAP and Lu-BiOncoFAP at different molar amounts (3 vs. 250 nmol/kg) of injected ligand was studied via SPECT/CT in mice bearing subcutaneous HT-1080.

Time after Synthesis and Time after Injection Do Not Affect Diagnostic Quality of [F]F-PSMA 1007 PET.

PET imaging using PSMA ligands is increasingly used for staging in prostate cancer patients in different clinical indications. Unlike [Ga]Ga-labeled PSMA ligands, fluorinated compounds can be produced in large amounts; thus, they can be used for a higher number of patients. One concern is that in patients studied a long time after synthesis (TaS) or time after injection (TaI), the specific activity may decline; thus, the signal may be lower in these patients.

Incremental diagnostic value of [F]tetrafluoroborate PET-CT compared to [I]iodine scintigraphy in recurrent differentiated thyroid cancer.

Introduction: Efficient therapy of recurrent differentiated thyroid cancer (DTC) is dependent on precise molecular imaging techniques targeting the human sodium iodide symporter (hNIS), which is a marker both of thyroid and DTC cells. Various iodine isotopes have been utilized for detecting DTC; however, these come with unfavorable radiation exposure and image quality ([I]iodine) or limited availability ([I]iodine). In contrast, [F]tetrafluoroborate (TFB) is a novel radiolabeled PET substrate of hNIS, results in PET images with high-quality and low radiation doses, and should therefore be suited for imaging of DTC.

Development of a novel, fibrin-specific PET tracer.

Fibrin deposition is observed in several diseases such as atherosclerosis, deep vein thrombosis, and also tumors, where it contributes to the formation of mature tumor stroma. The aim of this study was to develop a gallium-labeled peptide tracer on the basis of the fibrin-targeting peptide Epep for PET imaging of fibrin deposition. For this purpose, the peptide Epep was modified with a NOTA moiety for radiolabeling with Ga and Ga and compared with the earlier validated In-DOTA-Epep tracer.

Radioligand Therapy With 177Lu-PSMA-617 as A Novel Therapeutic Option in Patients With Metastatic Castration Resistant Prostate Cancer.

Background: Despite progress in treatment of metastatic castration-resistant prostate cancer (mCRPC), new approaches are urgently needed. Recently theranostic concepts using radiolabeled ligands of the prostate-specific membrane antigen (PSMA) have been developed for diagnostics and therapy of patients with advanced mCRPC. The aim of this study was to evaluate tumor response, adverse effects, and survival in patients undergoing radioligand therapy with Lu-PSMA-617.

Response and Tolerability of a Single Dose of 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer: A Multicenter Retrospective Analysis.

Unlabelled: Radiolabeled prostate-specific membrane antigen (PSMA) ligands represent a true theranostic concept for diagnosis and therapy in patients with relapsed or metastatic prostate cancer. The aim of this study was to evaluate the response to and tolerability of a single dose of (177)Lu-PSMA-617 in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods: The data of 82 consecutive patients (median age, 73 y; range, 43-87 y) with mCRPC who received a single dose of (177)Lu-PSMA-617 (mean, 5.

Early side effects and first results of radioligand therapy with (177)Lu-DKFZ-617 PSMA of castrate-resistant metastatic prostate cancer: a two-centre study.

Background: Radioligand therapy (RLT) with (177)Lu-DKFZ-617 PSMA (Lu-PSMA) (prostate-specific membrane antigen) is a novel targeted therapy of metastatic prostate cancer. We analysed retrospectively the early side effects and the response rate in the first patients, who received a therapy with Lu-PSMA in our departments.

Methods: RLT was performed in ten hormone- and/or chemo-refractory patients with distant metastases and progressive disease (mean age 73.

Non-invasive monitoring of tumor-vessel infarction by retargeted truncated tissue factor tTF-NGR using multi-modal imaging.

The fusion protein tTF-NGR consists of the extracellular domain of the thrombogenic human tissue factor (truncated tissue factor, tTF) and the peptide GNGRAHA (NGR), a ligand of the surface protein CD13 (aminopeptidase N), upregulated on endothelial cells of tumor vessels. tTF-NGR preferentially activates blood coagulation within tumor vasculature, resulting in tumor vessel infarction and subsequent tumor growth retardation/regression. The anti-vascular mechanism of the tTF-NGR therapy approach was verified by quantifying the reduced tumor blood-perfusion with contrast-enhanced ultrasound, the reduced relative tumor blood volume by ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging, and by in vivo-evaluation of hemorrhagic bleeding with fluorescent biomarkers (AngioSense(680)) in fluorescence reflectance imaging.

Efficient synthesis of a fluorine-18 labeled biotin derivative.

Introduction: The natural occurring vitamin biotin, also known as vitamin H or vitamin B(7), plays a major role in various metabolic reactions. Caused by its high binding affinity to the protein avidin with a dissociation constant of about 10(-15)M the biotin-avidin system was extensively examined for multiple applications. We have synthesized a fluorine-18 labeled biotin derivative [(18)F]4 for a potential application in positron emission tomography (PET).

Radiosynthesis of a ⁶⁸Ga labeled matrix metalloproteinase inhibitor as a potential probe for PET imaging.

A matrix metalloproteinase inhibitor based on a barbiturate scaffold was conjugated with a cyclooctyne derivative of the (radio)metal chelator DOTA via strain induced azide alkyne cycloaddition. Subsequent radiolabeling with (68)Ga yielded the corresponding radiometal labeled target compound (68)Ga-4 with a yield of 87% (decay corrected). The target molecule was also synthesized by a second synthesis route, the reaction of a pre-labeled (68)Ga-cyclooctyne-DOTA derivative (68)Ga-1 with an azide bearing barbiturate 3.

The influence of halogen substituents on the course of hydrogallation and hydroalumination reactions.

Treatment of trimethylsilylethynylbenzene derivatives with HGaCl(2) afforded products, [C(6)H(6-x){C(H)=C(SiMe(3))GaCl(2)}(x)], in which by a very fast cis/trans-rearrangement the Ga and H atoms occupied opposite sides of the resulting C=C double bonds. The stability of the cis-forms considerably increased upon application of 1,3-dibromo- and pentafluorophenylalkyne derivatives. Two pairs of cis/trans-isomers could be characterized by crystal structure determinations and allow the direct comparison of structural parameters.

Reducing Ga-H and Ga-C bonds in close proximity to oxidizing peroxo groups: conflicting properties in single molecules.

Treatment of [Li(H(2)Ga{CH(SiMe(3))(2)}(2))]2 OEt(2) (12 OEt(2)) with two equivalents of tert-butyl hydrogen peroxide, H-O-O-CMe(3), afforded the organogallium peroxide [({(Me(3)Si)(2)HC}(2)Ga(OH)(OOCMe(3))Li)(2)] (3), which possesses oxidizing peroxo groups in close proximity to reducing Ga-C bonds. The lithium atoms of the dimeric formula units are coordinated by both oxygen atoms of the peroxides and by two hydroxo groups. The cleavage of the Ga--C bond was not observed, even when an excess of H-O-O-CMe(3) was applied.

cis/trans Isomerism of hydroalumination and hydrogallation products-reflections on stability and rearrangement mechanism.

Treatment of (silylalkynyl)benzenes with (Me(3)C)(2)Ga-H afforded stable cis-addition products, for example, (Me(3)C)(2)Ga-C(SiMe(3))=C(H)-C(6)H(5) (1), while spontaneous cis/trans rearrangement was observed for sterically less shielded gallium hydrides. The corresponding trans-di(tert-butyl)gallium compounds (13, 14) were obtained by the reaction of C(6)H(6-n)[C(H)=C(SiMe(3))GaCl(2)](n) (11, 12) with LiCMe(3). In contrast, spontaneous isomerization took place upon reaction of (Me(3)C)(2)Al-H with phenyltrimethylsilylethyne.

Twofold hydrogallation of C triple bonds c triple bonds by H-GaCl(2)-synthesis of chelating Lewis acids and their application in adduct formation.

The twofold addition of Ga-H to Ctriple bonds C triple bonds (hydrogallation) did not succeed by treatment of alkynes with an excess of dialkylgallium hydrides. In contrast, double hydrogallation was easily achieved by the reactions of H-GaCl(2) with trimethylsilyl-substituted alkynes [trimethylsilylphenylethyne and 1,4-bis(trimethylsilylethynyl)benzene] in appropriate stoichiometric ratios. The monoalkyne yielded the compound [H(5)C(6)-CH(2)-C(SiMe(3))(GaCl(2))(2)](2), 1, which was only sparingly soluble in n-hexane.

Hydrogallation of alkynes with H-GaCl2: formation of organoelement dichlorogallium compounds potentially applicable as chelating Lewis acids.

Treatment of trimethylsilylethynylbenzenes C6H6-x(C[TRIPLE BOND]C-SiMe3)x(x=1-3) with the hydridodichlorogallium compound H-GaCl2 afforded, almost quantitatively, the alkenylphenyl compounds C6H6-x[C(H)C(SiMe3)-GaCl2]x[x=1 (6), 2 (7), and 3 (8)] by hydrogallation. Only compound 6 was readily soluble in n-hexane; it formed dimers via Ga-Cl bridges. The bisalkenyl compound 7 was only sparingly soluble; its molecular structure consisted of a singular dimeric formula unit with a cyclophane-type constitution and two bridging Ga 2Cl 2 heterocycles.

The reactions of dialkylgallium hydrides with tert-butylethynylbenzenes--a systematic investigation into the course of hydrogallation reactions.

The reactions of bis- and tris(tert-butylethynyl)benzenes with dialkylgallium hydrides afforded two different types of products. 1,4-Di(tert-butylethynyl)benzene and dialkylgallium hydrides R(2)GaH bearing relatively small substituents (R = Et, nPr) gave the expected addition products with each C triple bond C triple bond inserted into a Ga-H bond. The intact GaR(2) groups are attached to those carbon atoms which are in alpha-position to the benzene rings, and intermolecular Ga-C interactions led to the formation of one-dimensional coordination polymers.