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[ 18 F]tetrafluoroborate ([ 18 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 [ 18 F]TFB PET with high-activity posttherapeutic [ 131 I]iodine whole-body scintigraphy and SPECT/CT in recurrent DTC and with [ 18 F]FDG PET/CT in suspected dedifferentiation. Methods: Twenty-six patients treated with high-activity radioactive [ 131 I]iodine therapy (range, 5.00-10.23 GBq) between May 2020 and November 2022 were retrospectively included. Thyroid-stimulating hormone was stimulated by 2 injections of recombinant thyroid-stimulating hormone (0.9 mg) 48 and 24 h before therapy. Before treatment, all patients underwent [ 18 F]TFB PET/CT 40 min after injection of a median of 321 MBq of [ 18 F]TFB. To study tracer kinetics in DTC lesions, 23 patients received an additional scan at 90 min. [ 131 I]iodine therapeutic whole-body scintigraphy and SPECT/CT were performed at a median of 3.8 d after treatment. Twenty-five patients underwent additional [ 18 F]FDG PET. Two experienced nuclear medicine physicians evaluated all imaging modalities in consensus. Results: A total of 62 suspected lesions were identified; of these, 30 lesions were [ 131 I]iodine positive, 32 lesions were [ 18 F]TFB positive, and 52 were [ 18 F]FDG positive. Three of the 30 [ 131 I]iodine-positive lesions were retrospectively rated as false-positive iodide uptake. Tumor-to-background ratio measurements at the 40- and 90-min time points were closely correlated (e.g., for the tumor-to-background ratio for muscle, the Pearson correlation coefficient was 0.91; P < 0.001; n = 49). We found a significant negative correlation between [ 18 F]TFB uptake and [ 18 F]FDG uptake as a potential marker for dedifferentiation (Pearson correlation coefficient, -0.26; P = 0.041; n = 62). Conclusion: Pretherapeutic [ 18 F]TFB PET/CT may help to predict the positivity of recurrent DTC lesions on [ 131 I]iodine scans. Therefore, it may help in the selection of patients for [ 131 I]iodine therapy. Future prospective trials for iodine therapy guidance are warranted. Lesion [ 18 F]TFB uptake seems to be inversely correlated with [ 18 F]FDG uptake and therefore might serve as a dedifferentiation marker in DTC., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

We studied the antitumor efficacy of a combination of 177 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. Methods: The biodistribution of 177 Lu-OncoFAP and 177 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.hFAP tumors, and self-absorbed tumor and organ doses were calculated. The in vivo anticancer effect of 5 MBq of the radiolabeled preparations was evaluated as monotherapy or in combination with L19-IL2 in subcutaneously implanted HT-1080.hFAP and SK-RC-52.hFAP tumors. Tumor samples from animals treated with 177 Lu-BiOncoFAP, L19-IL2, or both were analyzed by mass spectrometry-based proteomics to identify therapeutic signatures on cellular and stromal markers of cancer and on immunomodulatory targets. Results: 177 Lu-BiOncoFAP led to a significantly higher self-absorbed dose in FAP-positive tumors (0.293 ± 0.123 Gy/MBq) than did 177 Lu-OncoFAP (0.157 ± 0.047 Gy/MBq, P = 0.01) and demonstrated favorable tumor-to-organ ratios at high molar amounts of injected ligand. Administration of L19-IL2 or 177 Lu-BiOncoFAP as single agents led to cancer cures in only a limited number of treated animals. In 177 Lu-BiOncoFAP-plus-L19-IL2 combination therapy, complete remissions were observed in all injected mice (7/7 complete remissions for the HT-1080.hFAP model, and 4/4 complete remissions for the SK-RC-52.hFAP model), suggesting therapeutic synergy. Proteomic studies revealed a mechanism of action based on the activation of natural killer cells, with a significant enhancement of the expression of granzymes and perforin 1 in the tumor microenvironment after combination treatment. Conclusion: The combination of OncoFAP-based radioligand therapeutics with concurrent targeting of interleukin 2 shows synergistic anticancer effects in the treatment of FAP-positive tumors. This experimental finding should be corroborated by future clinical studies., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

PET imaging using PSMA ligands is increasingly used for staging in prostate cancer patients in different clinical indications. Unlike [ 68 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. In this study, we investigated a potential effect of TaS and TaI on image quality. In total, 134 consecutive patients were included in this retrospective analysis on the effect of TaS and TaI on uptake in prostate cancer lesions. All the patients underwent [ 18 F]F-PSMA-1007 PET-CT from 99 min up to 549 min after tracer quality control. TaS and TaI were compared to the quantitative tumoral uptake parameters SUVmax and SUVpeak. In a second exploratory part of the analysis, TaS and TaI were correlated to a physiological tracer uptake in different organs. TaS and TaI did not affect the SUVmax and SUVpeak in tumor lesions in [ 18 F]F-PSMA-1007 PET. The physiological uptake in salivary glands, lacrimal glands and the ganglia, spleen and urine was not significantly correlated to TaS or TaI; in contrast to the mean liver uptake, showing a weak, but significant correlation to TaS. The [ 18 F]F-PSMA-1007 uptake in prostate cancer lesions is not significantly dependent on the TaS and TaI. These results are extremely reassuring when performing [ 18 F]F-PSMA-1007 PET a considerable time after synthesis.

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 ([ 131 I]iodine) or limited availability ([ 124 I]iodine). In contrast, [ 18 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. The aim of the present study was to compare the diagnostic performance of [ 18 F]TFB-PET to the clinical reference standard [ 131 I]iodine scintigraphy in patients with recurrent DTC., Methods: Twenty-five patients with recurrent DTC were included in this retrospective analysis. All patients underwent [ 18 F]TFB-PET combined with either CT or MRI due to newly discovered elevated TG levels, antiTG levels, sonographically suspicious cervical lymph nodes, or combinations of these findings. Correlative [ 131 I]iodine whole-body scintigraphy (dxWBS) including SPECT-CT was present for all patients; correlative [ 18 F]FDG-PET-CT was present for 21 patients. Histological verification of [ 18 F]TFB positive findings was available in 4 patients., Results: [ 18 F]TFB-PET detected local recurrence or metastases of DTC in significantly more patients than conventional [ 131 I]iodine dxWBS and SPECT-CT (13/25 = 52% vs. 3/25 = 12%, p = 0.002). The diagnosis of 6 patients with cervical lymph node metastases that showed mildly increased FDG metabolism but negative [ 131 I]iodine scintigraphy was changed: [ 18 F]TFB-PET revealed hNIS expression in the metastases, which were therefore reclassified as only partly de-differentiated (histological confirmation present in two patients). Highest sensitivity for detecting recurrent DTC had the combination of [ 18 F]TFB-PET-CT/MRI with [ 18 F]FDG-PET-CT (64%)., Conclusion: In the present cohort, [ 18 F]TFB-PET shows higher sensitivity and accuracy than [ 131 I]iodine WBS and SPECT-CT in detecting recurrent DTC. The combination of [ 18 F]TFB-PET with [ 18 F]FDG-PET-CT seems a reasonable strategy to characterize DTC tumor manifestations with respect to their differentiation and thereby also individually plan and monitor treatment. Future prospective studies evaluating the potential of [ 18 F]TFB-PET in recurrent DTC are warranted.

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 67 Ga and 68 Ga and compared with the earlier validated 111 In-DOTA-Epep tracer. In vitro binding assays of 67 Ga-NOTA-Epep displayed an enhanced retention as compared to previously published data showing binding of 111 In-DOTA-Epep to human (84.0 ± 0.6 vs 66.6 ± 1.4 %Dose) and mouse derived fibrin clots (83.5 ± 1.7 vs 74.2 ± 2.4% Dose). In vivo blood kinetics displayed a bi-phasic elimination profile (t 1/2 , α  = 2.6 ± 1.0 minutes and t 1/2 , β  = 15.8 ± 1.3 minutes) and ex vivo biodistribution showed low blood values at 4 hours post injection and a low uptake in nontarget tissue (<0.2 %ID/g; kidneys, 1.9%ID/g). In conclusion, taking into account the ease of radiolabeling and the promising in vitro and in vivo studies, gallium-labeled Epep displays the potential for further development towards a PET tracer for fibrin deposition., (Copyright © 2017 John Wiley & Sons, Ltd.)

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, 5.9 ± 0.5 GBq) were retrospectively analyzed. Data were collected at baseline and 8 wk after therapy. (68)Ga-PSMA-11 PET/CT was performed on all patients to verify sufficient PSMA expression. Bone, lymph node, liver, and lung metastases were present in 99%, 65%, 17%, and 11% of the patients, respectively. Tolerability and response were evaluated using hematologic parameters, renal scintigraphy, clinical data, and the prostate-specific antigen (PSA) level at baseline and 8 wk after therapy application., Results: Six patients died, and 2 patients dropped out because they were not willing to continue therapy and follow-up. The complete dataset of 74 patients was available for analysis. Forty-seven patients (64%) showed a PSA decline, including 23 (31%) with a decline by more than 50%. Thirty-five patients (47%) had stable disease: the change in their PSA level ranged from less than a 50% decline to less than a 25% rise. Seventeen patients (23%) had progressive disease: their PSA level rose by more than 25%. There were no significant changes in hemoglobin, white blood cells, creatinine, or tubular extraction rates indicative of toxicity. There was a significant but mild decrease in platelets, but the median value was still within the reference range., Conclusion: This retrospective multicenter analysis suggests that radioligand therapy with (177)Lu-PSMA-617 is safe and well tolerated and has a considerable effect on PSA level. Therefore, it offers an additional therapeutic option for patients with mCRPC. These data may justify further prospective randomized studies to evaluate and prove the clinical benefit in terms of survival and quality of life., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

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., Methods: Fifty therapies using Lu-PSMA-617 were performed in 28 consecutive patients with mCRPC and exhausted conventional therapeutic options (median age, 73.4 years; range, 45-87 years). Data were retrospectively analyzed with focus on response, safety, and survival. The median overall survival was compared with that of a recent historical patient cohort treated with best supportive care prior to availability of Lu-PSMA-617., Results: Any PSA decline occurred in 59% and 75% of patients after 1 and 2 therapies. Moreover, a PSA decline of 50% or greater occurred in 32% and 50%. Therapies were well tolerated. Hematologic and renal parameters changed insignificantly; permanent xerostomia or other safety-related toxicity did not occur. The estimated median survival was 29.4 weeks, significantly longer than survival in the historical best supportive care group (19.7 weeks [hazard ratio, 0.44; 95% confidence interval, 0.20-0.95]; P = 0.031)., Conclusions: Results from 50 therapies show that radioligand therapy with Lu-PSMA-617 is effective and well tolerated and seems to increase overall survival. A future randomized controlled prospective study will be necessary to confirm these results.

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 73.5 years). (68)Ga-PSMA HBED-CC PET/CT was performed in all patients prior to RLT. The median PSA level prior to the therapy was 298.5 ng/ml (range 5-853 ng/ml). All patients received CBC, renal and liver function tests the day before and 2 days after application (mean administered activity 5.6 GBq, range 4.1-6.1 GBq), followed by further tests every 2 weeks. All patients were contacted by telephone every week regarding side effects or any positive and negative changes., Results: Eight weeks after the therapy, seven patients (70 %) experienced a PSA decline, of whom six experienced more than 30 % and five more than 50 %. Three patients showed a progressive disease according to the PSA increase. No patient experienced any side effects immediately after injection of Lu-PSMA. Relevant hematotoxicity (grade 3 or 4) occurred 7 weeks after the administration in just one patient. The same patient showed a leucopenia grade 2. Two patients showed a disturbance of only 1 hematologic cell line, whereas one patient showed a reduction of grades 1 and 2 in leucocytes and thrombocytes, respectively. Six patients did not show any hematotoxicity during the 8 weeks after therapy. There was no relevant nephrotoxicity (grade 3 or 4)., Conclusions: Our initial results indicate that RLT with Lu-PSMA is safe and seems to have low early side-effect profile. A relevant PSA decline was detected in 70 % of patients.

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. The accumulation of tTF-NGR within the tumor was proven by visualizing the distribution of the iodine-123-labelled protein by single-photon emission computed tomography. Use of these multi-modal vascular and molecular imaging tools helped to assess the therapeutic effect even at real time and to detect non-responding tumors directly after the first tTF-NGR treatment. This emphasizes the importance of imaging within clinical studies with tTF-NGR. The imaging techniques as used here have applicability within a wider scope of therapeutic regimes interfering with tumor vasculature. Some even are useful to obtain predictive biosignals in personalized cancer treatment.

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)., Methods: Mesylate precursor 3 was obtained by an efficient two-step reaction via a copper catalyzed azide-alkyne cycloaddition (CuAAC) from easily accessible starting materials. [(18)F]4 was successfully synthesized by a nucleophilic radiofluorination of precursor 3. A biodistribution study by means of small-animal PET imaging in wt-mice was performed and serum stability was examined., Results: Compound [(18)F]4 was obtained from precursor compound 3 with an average specific activity of 16GBq/μmol within 45min and a radiochemical yield of 45±5% (decay corrected). [(18)F]4 demonstrated only negligible decomposition in human serum. A qualitative binding study revealed the high affinity of the synthesized biotin derivative to avidin. Blocking experiments with native biotin showed that binding was site-specific. Biodistribution studies showed that [(18)F]4 was cleared quickly and efficiently from the body by hepatobiliary and renal elimination., Conclusion: An efficient synthesis for [(18)F]4 was established. In vivo characteristics were determined and demonstrated the pharmacokinetic behaviour of [(18)F]4., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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. This approach offers a valuable alternative for providing the desired (68)Ga-radiolabeled target compound. But, in this case, the strain induced cycloaddition of the reported pre-labeled cyclooctyne-DOTA derivative (68)Ga-1 with azides was proven to be slow at room temperature and heating was necessary for acceptable reaction times., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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. For the first time an equilibrium was detected between cis- and trans-forms in solution. Treatment of 1,4-di(tert-butylalkynyl)benzene with HAlR(2) (R = CMe(3), CH(2)CMe(3)) afforded cyclophane-type molecules by the release of AlR(3). Only the neopentyl derivative could be isolated and characterized by crystal structure determination. In contrast, the dibromo compound, 1,4-Br(2)-2,5-(Me(3)CC[triple bond]C)(2)C(6)H(2), yielded the simple addition product, C(6)H(2)Br(2){C(AlR(2))=C(H)CMe(3)}(2) (R = CMe(3)). Condensation was hindered in this case by intramolecular Al-Br interactions. Surprisingly, the simple addition product was also isolated from the reaction of 1,4-(Me(3)CC[triple bond]C)(2)C(6)H(4) with the relatively small hydride HAlEt(2). Solid-state NMR spectra of the product revealed strong intermolecular Al-C interactions involving the negatively charged terminal vinylic carbon atoms, to give one-dimensional coordination polymers.

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. Instead, the adduct [{(Me(3)Si)(2)HC}(2)Ga(OH)(OOCMe(3))(2)Li(2)(HOOCMe(3))] (4) was isolated, which has an intact H-O-O-CMe(3) molecule terminally attached to lithium. A similar structural motif was found for the compound [(LiOOCMe(3))(2)(HOOCMe(3))(2)] (5). The trihydrido gallanate [Li(H(3)Ga-{CH(SiMe(3))(2)})]OEt(2) (2) yielded the unique peroxide [({(Me(3)Si)(2)HC}--Ga(H)(OOCMe(3))(2)Li)(2)] (6) under similar conditions that possesses Ga-C and even more reactive Ga-H bonds beside peroxo groups. It decomposed at room temperature by the insertion of oxygen atoms into the Ga-H bonds and the formation of [({(Me(3)Si)(2)HC}-Ga(OH)(OCMe(3))(OOCMe(3))Li)(2)] (7), which was isolated in a low yield. Further decomposition gave the complete degradation of all peroxo groups with the formation of a relatively complicated Li(4)Ga(4)O(8) cage (8).

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 overall structure may be described by a molecular box formed by a large macrocycle comprising 22 Ga, C, and Cl atoms. Compound 8 proved to be insoluble in hydrocarbon solvents. Its molecular structure could not be detected. Extraction of the solid raw products of 7 and 8 with diethyl ether yielded small quantities of the ether adducts C6H6-x[C(H)C(SiMe3)-GaCl2(OEt2)]x(x=2, 3) [7(OEt2)2 and 8(OEt2)3], both of which are monomeric because of the coordinative saturation of their gallium atoms. The tetraalkyne 1,2,4,5-tetrakis(trimethylsilylethynyl)benzene gave a different reaction course. Complete hydrogallation resulted in the release of 2 equiv of GaCl3, and neighboring alkenyl groups of the product 9 were connected by GaCl bridges to form seven-membered heterocycles and an overall tricyclic compound. Compound 9 was characterized as a diethyl ether adduct.

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. Crystal structure determination revealed a dimeric formula unit possessing two parallel Ga(2)Cl(2) heterocycles in the solid state. Treatment of the dialkyne with four equivalents of the hydride gave a colorless precipitate, which was completely insoluble in hydrocarbons. Addition of diethyl ether to both products afforded soluble and monomeric etherates 1(OEt(2))(2) and 2 in which the two or four gallium atoms, respectively, were coordinated by ether molecules. Preliminary experiments with simple Lewis bases showed the principle capability of 1 to act as an effective chelating Lewis acid. Adducts of the type [H(5)C(6)-CH(2)-C(SiMe(3))(GaCl(2))(GaClX)(micro-Cl)]- (4-6) resulted upon treatment with halide ions (X = Cl, Br, I).

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. In this case the cis isomer (17) was detected only at low temperature, while the trans product (18) formed quantitatively above 0 degrees C. Quantum-chemical calculations showed that the trans forms are thermodynamically favored, essentially caused by a better mesomeric interaction of the C==C double bonds with the phenyl groups, a smaller steric stress in the molecules, and a short bonding contact of the coordinatively unsaturated Al or Ga atoms to C-H bonds of the aromatic rings. The rotation about the C=C double bonds follows a zwitterionic mechanism, and the relatively small rotational barrier is further lowered by an interaction to a Lewis acidic lithium cation.

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. In contrast secondary reactions with the release of the corresponding trialkylgallium derivatives GaR(3) (R = Et, nPr, iPr, CH(2)tBu, tBu) were observed for all hydrogallation reactions involving the trisalkyne 1,3,5-tris(tert-butylethynyl)benzene. A similar reaction was observed upon treatment of the 1,4-bisalkyne with a dialkylgallium hydride bearing a relatively bulky substituent (R = neopentyl). Cyclophane type molecules are formed in all these cases with two or three gallium atoms in the bridging positions between both benzene rings.