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A novel procedure for ambient-pressure synthesis of pentacarbonyltechnetium halides [99TcX(CO)5] (X = Cl, Br) was developed. The procedure is based on treatment of K2[99TcX6] with a mixture of HCOOH and H2SO4 on heating. With X = I, a mixture of [99TcI(CO)5] and [99TcI(CO)4]2 was obtained. The products were characterized by elemental analysis and by 99Tc NMR and IR spectroscopy.

Purpose The aim of this study was to investigate the biodistribution and localization of an anti-inflammatory nonapeptide coupled to synovial targeting peptide (HAP-1) in rat adjuvant-induced arthritis. Procedure N e -functionalized histidine derivative was coupled to the N-terminus of core peptide (CP) and HAP-1 to allow coupling of 99m Tc-tricarbonyl linker (Isolink). Synovial homing peptide HAP-1 was linked to CP through a peptide bond prior to labeling with 99m Tc. Peptides were purified by high-performance liquid chromatography, characterized by mass spectrometry, radiolabeled and injected into normal and arthritic rats to determine biodistribution and localization. Results Gamma scintigraphy imaging showed that the biodistribution of all 99m Tc-labeled peptides were higher in the arthritic joints compared with the normal nonarthritic joints, at all three time points (10 min, 1 h, 3 h postinjection) and attributed to increased blood flow to inflammatory sites. HAP-1 and CP–HAP-1 showed a greater uptake and localization to arthritic joints compared with controls. There was no difference in the physiological biodistribution of these agents in the heart, kidneys and the bladder. Conclusions This study highlights the versatility of using the His derivative linker for 99m Tc tagging of a variety of peptides. It also demonstrates greater peptide localization and thereby bioavailability of therapeutic peptides to inflamed joints following specific conjugation to homing peptides. The ability to localize peptide/drugs to inflamed synovium has important therapeutic implications.

[(Methyl-pyridin-2-ylmethyl-amino)-methyl]-phosphonic acid is a new bifunctional chelator for the fac-[(99m)Tc(CO(3))](+) core which can be linked to biomolecules via formation of phosphonic acid esters. Its synthesis and the coupling to model alcohols and to a bioactive molecule (cobinamide) are described. The rhenium complexes [Re(CO)(3)L] of the esters have been prepared and characterized, one of them by X-ray crystallography. The model esters could be labeled with [(99m)Tc(OH(2))(3)(CO)(3)](+) under mild conditions and relatively low ligand concentration with >97% yield and only one isomer formed. The (99m)Tc-labeled cobinamide analog was a mixture of four isomers. It bound strongly to transcobalamin I (TC I, haptocorrin) but only slightly to transcobalamin II (TC II) and intrinsic factor (IF), reflecting the binding abilities of cobinamide. Biodistribution studies in mice with B(16) melanoma exhibited fast clearance with no specific tissue binding.

Labelling of the hydrophobic surfactant protein B (SP-B) under non-reducing conditions was achieved with [ 99m Tc(CO) 3 (H 2 O) 3 ] + prepared according to Alberto et al. (JACS, 1998). The binding of radioactivity was protein-specific, with an overall radiochemical yield of 50%. Gel electrophoresis and Westernblot analyses showed no structural changes of SP-B. Spreading properties and surface activity of 99m Tc-labelled SP-B in an air/water interface coincided with those of unlabelled SP-B. 99m Tc-SP-B seems to be a promising agent to observe surfactant spreading under clinical conditions. Background: Therapeutic results for surfactant instillation in clinical trials are conflicting. The 99m Tc-labelling of surfactant would allow to observe its spreading in the lung under clinical conditions. Methods: [ 99m Tc(CO) 3 (H 2 O) 3 ] + was prepared as described by Alberto et al. (JACS, 1998). This carbonyl complex was used for the direct labelling of surfactant protein B (SP-B) under non-reductive conditions by direct incubation with SP-B at elevated temperature followed by extraction into CHCl 3 /MeOH. Results: The hydrophobic protein SP-B was labelled with [ 99m Tc(CO) 3 (H 2 O) 3 ] + . An overall radiochemical yield of about 50% was achieved. HPLC-analysis revealed a single radiolabelled species according to UV elution profile of SP-B, supported by paper and size exclusion chromatography. Gel electrophoresis confirmed that the dimer structure of SP-B was preserved. Spreading properties of 99m Tc-labelled SP-B in an air/water interface coincided with those of unlabelled SP-B. Spreading of radioactivity observed in a glass trough of 26 cm × 27 cm with a gamma camera was completed during the first 7–9 sec after application of 99m Tc-labelled SP-B. The corresponding decrease of surface tension to 45 mN/m at the peripheral surface tension sensors took 7 sec ± 2 sec (MEAN ± STD; n = 3). Conclusions: Direct and specific 99m Tc-labelling of the hydrophobic surfactant protein B was achieved using the [ 99m Tc(CO) 3 (H 2 O) 3 ] + precursor. This procedure can easily be used to prepare specifically labelled surfactant mixtures with spreading properties that coincide with those of unlabelled surfactant.

The biological evaluation of half-sandwich (99m)Tc-complexes that surrogate iodobenzamide with a high affinity for melanin tumor tissue is described. We have synthesized via retro Diels-Alder reaction two models of (99m)Tc complexes which possess the piano stool [Cp(99m)Tc(CO)(3)] motif instead of a phenyl ring as in the original iodobenzamide (123)I-N-(N-benzylpiperidin-4-yl)-2-iodobenzamide (2-IBP) and N-(2-diethylaminoethyl)-4-iodobenzamide (BZA). Diels-Alder products 2a-b (HCp-CONHR)(2) (2a, R=2-diethylaminoethyl; 2b, R=benzylpiperidin-4-yl) were prepared and reacted with fac-[(99m)Tc(H(2)O)(3)(CO)(3))](+) 1 in water to produce the corresponding (99m)Tc complexes [(2a)(99m)Tc(CO)(3))] 4a and [(2b)(99m)Tc(CO)(3))] 4b. The structures of the (99m)Tc complexes on the no-carrier-added level have been confirmed by chromatographic comparison with the corresponding rhenium complexes 3a and 3b, macroscopically characterized by IR, NMR, ESI-MS and X-ray crystallography for 3a [triclinic, P-1, a=7.3518(1) A, b=8.0309(2) A, c=17.5536(3) A, alpha=99.1260(5) degrees, beta=90.4215(14) degree , gamma=117.0187(11) degrees]. The radioconjugate 4b showed good in vitro stability. In murine melanoma B16F1 cells, significant cellular uptake (43.9% of the total applied activity) was attained after 4 h at 37 degrees C with about 50% of the cell-associated radioactivity being internalized in the cells (22% of the applied activity). Furthermore, in melanoma-bearing C57BL6 mice, tumor uptake values of 3.39+/-0.50 %ID g(-1) and 3.21+/-0.26 %ID g(-1) at 1 and 4 h postinjection, respectively, were observed indicating a good retention of 4b in the tumor.

s for Symposium on Technetium and Other Radiometals in Chemistry and Medicine (TERACHEM 2014), September 10–13, 2014 Session A1. Technetium and Rhenium in Coordination Chemistry

105Rhodium(III) complexes with three different acyclic tetrathioether ligands containing pendant carboxylic acid groups have been synthesized and characterized. The complexes were evaluated for stability under physiological conditions and the most promising complexes were evaluated in vivo in normal mice. The primary route of clearance for these complexes was the renal/urinary system, consistent with the presence of pendant carboxylate groups. The results indicate that the cis-[Rh(III)Cl2(2,5,8,11-tetrathiadodecane-1,12-dicarboxylic acid)]+ complex shows the most promising in vivo characteristics on which to base a potential therapeutic radiopharmaceutical.