Lipophilic Complex Research Articles

Synthesis and biodistribution of a novel 99mTc-DMSA-metronidazole ester as a potential tumor hypoxia imaging agent

The dimercaptosuccinic acid metronidazole ester (DMSAMe) was synthesized and radiolabeled with 99mTc to form the 99mTc-DMSAMe complex in high yield. The radiochemical purity of the 99mTc-DMSAMe complex was over 90%, as measured by TLC and by HPLC, without any notable decomposition at room temperature over a period of 6 h. Its partition coefficient indicated that it was a lipophilic complex. The tumor cell experiment and the biodistribution in mice bearing S 180 tumor showed that the 99mTc-DMSAMe complex had a certain hypoxic selectivity and accumulated in the tumor with high uptake and good retention. The tumor/blood and tumor/muscle ratios increased with time, suggesting it would be a possible tumor hypoxia imaging agent.

Leukocyte-technetium-99m uptake in Crohn’s disease: Does it show subclinical disease?

To evaluate inflammatory activity in patients with Crohn's disease (CD) using technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) granulocyte scintigraphy. Twenty patients (7 male and 13 female) with CD and five healthy volunteers were selected for 99mTc-HMPAO granulocyte scintigraphy. The Crohn's Disease Activity Index (CDAI), blood tests and C-reactive protein (CRP) of each patient were performed 7 d before the scintigraphic images. The leukocytes were labeled according to the International Society of Radiolabeled Blood Elements (ISORBE) consensus protocol and the scintigraphic images, including single photon emission computed tomography, were obtained 30 min and 2 h after injection of the radiolabeled leukocytes. The labeling yield of the leukocytes with the lipophilic complex 99mTc-HMPAO was 55.0% +/- 10%. Six of the 20 patients (30%) presented congruent results for the three parameters investigated (CDAI, Scintigraphic Index and CRP). On the other hand, 14 patients (70%) did not show congruent results. There was no significant correlation between the indices analyzed according to the Spearman test (P > 0.05, n = 20). The results suggest that 99mTc-HMPAO-labeled leukocyte scintigraphy could be important for determining inflammatory activity in CD even in the absence of clinical symptoms.

Synthesis and biological evaluation of 99mTc-DHPM complex: a potential new radiopharmaceutical for lung imaging studies

In the recent years interests on dihydropyri- midinone and their analogues have increased potentially due to their wide range of pharmacological/biological activities. Synthesis, radiolabeling with technetium-99 m ( 99m Tc) and biological evaluation of 5-etoxycarbonyl-4-phenyl-6- methyl-3,4-dihydro-(1H)-pyrimidine-2-one (DHPM) were studied in this present work. After synthesis complexation of DHPM with 99m Tc was carried out using stannous chloride as the reducing agent. The complex ( 99m Tc-DHPM) was characterized by thin layer chromatography, radio-HPLC technique and determination of partition co-efficient. Radiochemical stability and particle size distribution of the complex were also measured. Biodistribution/scintigraphy studies were performed in rats and rabbits to evaluate the pharmacological characteristics of this complex. The radiochemical purity of the complex was over 95% as studied by thin layer chromatography and radio-HPLC. It was stable over 24 h at room temperature. Its partition coefficient indicated that it was a lipophilic complex. According to the European Pharmacopeia, (80% of 99m Tc labeled radiopharmaceutical ( 99m Tc-MAA) in the size range 10-50 lm, must be accumulated in the lungs 15 min after intravenous administration. In this study(85% of the 99m Tc- DHPM complex in the average size of 40 lm. Biodistribu- tion studies of 99m Tc-DHPM in rat revealed that the complex accumulated in the lung with high uptake and good retention after intravenous administration. Scintigraphic studies in rabbit also revealed that most of the administered radiola- beled complex was accumulated in the lungs and after 1 h slowly excreted through the renal system. The lung uptake (ID%/g) was 10.12, 9.67, 8.60 and 5.01 and the lung/liver ratio was 7.49, 2.88, 2.62 and 1.87 at 2, 15, 30 and 60 min post-injection, respectively. These results suggested that 99m Tc-DHPM could be suitable as a potential lung perfusion imaging agent. Further studies with 99m Tc-DHPM and its derivatives are warranted to develop new 99m Tc-labeled

Synthesis and Relaxometric Properties of Gadolinium(III) Complexes of New Triazine‐Based Polydentate Ligands

AbstractTwo new derivatives based on an s‐triazine structural motif were synthesized by attaching two 2,2′‐hydrazinylidenebis[acetic acid] moieties to the triazine ring to reach an overall heptadenticity for the complexation of lanthanide(III) cations. The remaining reactive site was exploited for the substitution with a functionizable amino group (see H4L1) and a lipophilic moiety (see H4L2). Luminescence‐lifetime determinations revealed the presence of a single H2O molecule coordinated for [Eu(L1)]. A complete 1H‐NMR relaxometric study was carried out for the octacoordinated [Gd(L1)] and [Gd(L2)] complexes. A remarkably long H2O residence lifetime (298τM=5.2 μs) was found by 17O‐NMR in the case of [Gd(L1)]. Micelle formation of the lipophilic complex [Gd(L2)] was evidenced, the critical micellization concentration (cmc) determined, and relaxometric properties of the system investigated.

Voltammetric Extraction of Heparin and Low-Molecular-Weight Heparin across 1,2-Dichloroethane/Water Interfaces

Heparin and low-molecular-weight heparin are voltammetrically extracted across 1,2-dichloroethane/water interfaces for the detection of these highly sulfated polysaccharides widely used as anticoagulants/antithrombotics in many medical procedures. A new heparin ionophore, 1-[4-(dioctadecylcarbamoyl)butyl]guanidinium, is the first to enable the voltammetric extraction of various polyanionic heparins with average molecular weights of up to approximately 20 kDa including those in commercial preparations (i.e., Arixtra (1.5 kDa), Lovenox (4.5 kDa), and unfractionated heparin (15 kDa), as well as chromatographically fractionated heparins (7, 9, 15, and 20 kDa)). Facilitated Arixtra extraction is fully and quantitatively characterized by micropipet voltammetry to propose that cooperative effects from strong heparin-binding capability and high lipophilicity of this ionophore are required for the formation of an electrically neutral and highly lipophilic complex of a heparin molecule with multiple ionophore molecules to be extracted into the nonpolar organic phase. At the same time, the participation of multiple ionophore molecules in interfacial complexation with a heparin molecule slows down its extraction across the interface. This kinetic limitation is enhanced by fast mass transfer at a micropipet-supported interface to compromise thermodynamically favorable selectivity for heparin and an important contaminant, oversulfated chondroitin sulfate, thereby requiring a macroscopic interface for sensing applications. Another highly lipophilic guanidinium ionophore, N,N-dioctadecylguanidinium, cannot completely extract even Arixtra, which indicates the importance of elaborate ionophore design for heparin extraction.

Natural lipophilic inhibitors of mitochondrial complex I are candidate toxins for sporadic neurodegenerative tau pathologies

Annonacin, a natural lipophilic inhibitor of mitochondrial complex I has been implicated in the etiology of a sporadic neurodegenerative tauopathy in Guadeloupe. We therefore studied further compounds representing the broad biochemical spectrum of complex I inhibitors to which humans are potentially exposed. We determined their lipophilicity, their effect on complex I activity in submitochondrial particles, and their effect on cellular ATP levels, neuronal cell death and somatodendritic redistribution of phosphorylated tau protein (AD2 antibody against pS396/pS404-tau) in primary cultures of fetal rat striatum. The 24 compounds tested were lipophilic (log P range 0.9–8.5; exception: MPP + log P = − 1.35) and potent complex I inhibitors ( IC 50 range 0.9 nM–2.6 mM). They all decreased ATP levels ( EC 50 range 1.9 nM–54.2 μM), induced neuronal cell death ( EC 50 range 1.1 nM–54.5 μM) and caused the redistribution of AD2 + tau from axons to the cell body ( EC 5 range 0.6 nM–33.3 μM). The potency of the compounds to inhibit complex I correlated with their potency to induce tau redistribution ( r = 0.80, p < 0.001). In conclusion, we propose that the widely distributed lipophilic complex I inhibitors studied here might be implicated in the induction of tauopathies with global prevalence.

Synthesis and biodistribution of a novel [99mTcN(PNP5)(DMCHDTC)]+ complex as a potential myocardial perfusion imaging agent

The [99mTcN(PNP5)(DMCHDTC)]+(DMCHDTC: 2,3-dimethyl cyclohexyl dithiocarbamate, PNP5:bis(dimethoxypropylphosphinoethyl)ethoxyethylamine) complex was synthesized through a ligand-exchange reaction. The two-step procedure involved the initial reaction of 99mTcO4− with succinic dihydrazide (SDH) as a donor of nitride nitrogen atom (N3−) in the presence of stannous chloride dihydrate as reducing agent and propylenediamine tetraacetic acid (PDTA) as complexant, followed by the addition of the PNP5 ligand and the DMCHDTC ligand. The radiochemical purity (RCP) of the product was over 90% as measured by thin layer chromatography (TLC). No decomposition of the complex at room temperature was observed over a period of 6h. Its partition coefficient indicated that it was a lipophilic complex. The electrophoresis results showed the complex was cationic. The biodistribution results in mice indicated that [99mTcN(PNP5)(DMCHDTC)]+ was significantly retained into the heart. The heart uptake (ID%/g) was 14.47, 12.23 and 8.76 at 5, 30 and 60min post-injection, respectively. The heart/liver, heart/lung and heart/blood ratios of the complex were 1.24, 3.62 and 23.05 at 60min post-injection, suggesting it will be a potential myocardial imaging agent.

Uptake of Hydrophobic Metal Complexes by Three Freshwater Algae: Unexpected Influence of pH

Cadmium forms neutral, lipophilic Cd(L)2(0) complexes with diethyldithiocarbamate (DDC) and with ethylxanthate (XANT). Uptake of these complexes bythree unicellularfreshwater green algae (Chlamydomonas reinhardtii, Chlorella fusca, and Pseudokirchneriella subcapitata) was determined at two pH values (7.0 and 5.5) and compared to uptake of the free, uncomplexed Cd2+ ion. Uptake of the lipophilic complexes over time, characterized by high initial uptake rates but tending toward a plateau after about 30 min, could be modeled successfully as the result of the following processes: first-order uptake from solution, partitioning of the accumulated Cd into two internal pools (labile and nonlabile), and first-order loss of Cd from the labile pool. At pH 7.0 initial uptake rates for both Cd(L)2(0) complexes were much higher than for Cd2+ alone (e.g., up to approximately 90 times higher for comparable dissolved Cd concentrations of approximately 0.4 nM). However, the initial uptake rates for the lipophilic complexes dropped dramatically when the pH was lowered from 7.0 to 5.5 (2- to 60-fold decrease, depending on the algal species and the nature of the neutral complex). Loss rates for the accumulated complexes also decreased atthe lower pH. The lipophilicity of the neutral complexes, as estimated from their octanol-water distribution coefficient (Dow), was not affected by the decrease in pH from 7.0 to 5.5. We thus conclude that the acidification of the external medium, i.e., the interaction of protons with the algal membrane, strongly affects algal membrane permeability.

Synthesis and biodistribution of a novel 99mTc nitrido dithiocarbamate complex containing ether group as a potential myocardial and brain imaging agent

In the present study, a novel 99mTc nitrido dithiocarbamate complex containing ether group, the bis(2-ethoxyethyl dithiocarbamato) nitrido 99mTc complex 99mTcN(EOEDTC)2 has been synthesized by the reduction of 99mTcO4− into [99mTcN]2+ with stannous chloride in the presence of succinic dihydrazide and propylenediamine tetraacetic acid, followed by the addition of the corresponding dithiocarbamate ligand. The radiochemical purity of the complex was over 90% as measured by thin layer chromatography (TLC). In vitro studies showed that the complex possessed good stability. Its partition coefficient indicated that it was lipophilic complex. The electrophoresis results showed the complex was neutral. Biodistribution in mice showed that the complex accumulated in the heart and brain with high initial uptake, suggesting the complex may lead to a further development of the radiopharmaceutical as a heart and brain perfusion tracer.

Application of the Ugi four-component reaction to the synthesis of ditopic bifunctional chelating agents

The Ugi four-component reaction (Ugi 4CR) was exploited for the first time to obtain in a single synthetic step bifunctional ditopic chelators by using DOTA monoamide (DOTAMA) derivatives as amino and acid components. A number of ditopic systems in which the two DOTAMA units are connected by a central alpha-acylaminoamide group were synthesized by reacting different aldehydes, isocyanides and two DOTAMA chelates containing amino and acid functionalities. Variation of the components allows the insertion of another functional group into the alpha-acylaminoamide skeleton for further conjugation to biomolecules. The optimal reaction conditions were found by using methanol as solvent and ultrasound irradiation at a power of 60 W (20 kHz) for 3 h. The Gd(III) complexes of the dimeric ligands L1 and L2 (bearing a cyclohexyl ring and an octadecyl chain on the central alpha-acylaminoamide moiety, respectively) were fully characterized in aqueous media by relaxometric techniques with varying temperature and magnetic field strength. The relaxivity of Gd(2)L1 and Gd(2)L2 (in the aggregated form), at 20 MHz and 310 K, are 5.6 and 20.0 mM(-1) s(-1), respectively. The enhanced value found for Gd(2)L2 indicates that this lipophilic complex forms micelles at concentrations <0.1 mM. Finally, the binding of Gd(2)L2 to human serum albumin (HSA) was investigated by proton relaxometry, and the affinity constant of the complex and the relaxivity of the macromolecular adduct (r(1p)(b) = 38.1 mM(-1) s(-1); 20 MHz and 310 K) derived.

Synthesis, In Vitro, and In Silico Evaluation of Organometallic Technetium and Rhenium Thymidine Complexes with Retained Substrate Activity toward Human Thymidine Kinase Type 1

Human cytosolic thymidine kinase (hTK1) has proven to be a suitable target for noninvasive imaging of cancer cell proliferation using radiolabeled substrates such as [ (18)F]fluorothymidine ([ (18)F]FLT). However, a thymidine tracer useful for single photon emission tomography (SPECT) based on the inexpensive radionuclide technetium-99m would be of significant interest. In this work, a series of thymidine derivatives labeled with the organometallic [M(CO) 3] (+) core (M = (99m)Tc, Re) were synthesized. Neutral, cationic, and anionic complexes were readily formed in aqueous media, and all were substrates of recombinant hTK1 when incubated with ATP. The neutral complexes were phosphorylated to a greater extent than the charged complexes. The extent of phosphorylation was further improved by increasing the spacer length separating thymidine and the organometallic core. A molecular dynamics simulation study performed with a modified hTK1 structure supported the experimental findings. In vitro cell internalization experiments performed in a human neuroblastoma cell line (SKNMC) showed low uptake of the charged complexes but significant uptake for the neutral, lipophilic complexes with a log P value >1.

Synthesis and biodistribution of a novel 99mTcN complex of ciprofloxacin dithiocarbamate as a potential agent for infection imaging

The ciprofloxacin dithiocarbamate (CPFXDTC) was synthesized and radiolabeled with [ 99mTcN] 2+ intermediate to form the 99mTcN-CPFXDTC complex in high yield (>95%). No decomposition of the complex at room temperature was observed over a period of 6 h. Its partition coefficient indicated that it was a good lipophilic complex. The bacterial binding assay studies showed 99mTcN-CPFXDTC had a better binding affinity as compared with 99mTc-ciprofloxacin. Biodistribution results in induced infection mice showed 99mTcN-CPFXDTC had higher uptake at the sites of infection and better abscess/blood ratio than that of 99mTc-ciprofloxacin, suggesting 99mTcN-CPFXDTC would be a novel potential infection imaging agent.

Synthesis of a novel 99mTc nitrido radiopharmaceutical with isopropyl xanthate, showing brain uptake

In the present study, isopropyl xanthate (IPXT) ligand was labeled with the [ 99mTc≡N] 2+ core successfully to obtain the 99mTcN(IPXT) 2 complex with high radiochemical purity. No decomposition of the complex at room temperature was observed over a period of 6 h. Its partition coefficient indicated that it was a good lipophilic complex. The electrophoresis results showed that the complex was neutral. Biodistribution in mice demonstrated that the complex accumulated in the brain with high uptake and good retention. The brain uptake (ID%/g) was 1.95, 1.58 and 1.86 at 5-, 30- and 60-min post-injection, respectively. As compared with other reported 99mTcN-xanthates, the 99mTcN(IPXT) 2 complex showed higher brain uptake and better brain retention, suggesting potential usefulness of the complex as a brain perfusion imaging agent.

188Re-loaded lipid nanocapsules as a promising radiopharmaceutical carrier for internal radiotherapy of malignant gliomas

Lipid nanocapsules (LNC) entrapping lipophilic complexes of (188)Re ((188)Re(S(3)CPh)(2)(S(2)CPh) [(188)Re-SSS]) were investigated as a novel radiopharmaceutical carrier for internal radiation therapy of malignant gliomas. The present study was designed to evaluate the efficacy of intra-cerebral administration of (188)Re-SSS LNC by means of convection-enhanced delivery (CED) on a 9L rat brain tumour model. Female Fischer rats with 9L glioma were treated with a single injection of (188)Re-SSS LNC by CED 6 days after cell implantation. Rats were put into random groups according to the dose infused: 12, 10, 8 and 3 Gy in comparison with blank LNC, perrhenate solution (4 Gy) and non-treated animals. The radionuclide brain retention level was evaluated by measuring (188)Re elimination in faeces and urine over 72 h after the CED injection. The therapeutic effect of (188)Re-SSS LNC was assessed based on animal survival. CED of (188)Re perrhenate solution resulted in rapid drug clearance with a brain T (1/2) of 7h. In contrast, when administered in LNC, (188)Re tissue retention was greatly prolonged, with only 10% of the injected dose being eliminated at 72 h. Rat median survival was significantly improved for the group treated with 8 Gy (188)Re-SSS LNC compared to the control group and blank LNC-treated animals. The increase in the median survival time was about 80% compared to the control group; 33% of the animals were long-term survivors. The dose of 8 Gy proved to be a very effective dose, between toxic (10-12 Gy) and ineffective (3-4 Gy) doses. These findings show that CED of (188)Re-loaded LNC is a safe and potent anti-tumour system for treating malignant gliomas. Our data are the first to show the in vivo efficacy of (188)Re internal radiotherapy for the treatment of brain malignancy.

Decreased secretory transport of a quarternary ammonium, TBuMA, across LLC-PK1 cells by the anionic kidney extract

The effect of organic anionic (OA) fractions of various rat organ tissues on the apparent partition coefficients (APC) of quarternary ammoniums (QAs) between n-octanol and phosphate buffer (pH 7.4) and QAs transport across the LLC-PK1 cell monolayer was examined. The OA fraction was prepared by filtering the aqueous extract of each tissue through an ion-exchange cartridge (Bond Elut C18). In the presence of OA fractions of liver and kidney extracts, substantial increase in APC was observed for tributylmethylammonium (TBuMA, Mw 200) and berberine (Mw 335), but not for triethylmethylammonium (TEMA, Mw 116) and tetraethylammonium (TEA, Mw 130). Because only QAs with higher Mw than a threshold (i.e., > 200) are known to form lipophilic ion-pair complexes with certain organic anions (e.g., bile salts such as taurodeoxycholate), above results are consistent with the hypothesis that only larger Mw QAs form lipophilic ion-pair complexes with endogenous organic anionic components of the liver and kidney extracts. Considering the comparable effect between the liver and kidney extracts on the APC of TBuMA regardless of far less (1/5) content of bile salts in the kidney extract, OAs other than bile salts in the kidney appear to contribute to the formation of lipophilic ion-pair complexes. Most interestingly, the secretory (i.e., basolateral to apical direction) transport of TBuMA and berberine across the LLC-PK1 cell monolayer was decreased by the cis-presence of the kidney extract, while remained unchanged for the transport of TEMA and TEA. The kidney extract had no effect on the absorptive (i.e., apical to basolateral direction) transport and cellular (LLC-PK1) accumulation of all of these QAs. Regardless of underlying mechanisms, it is notable that OA components of liver and kidney extracts influence the APC and secretory transport of QAs with Mw >200.

Root Uptake of Lipophilic Zinc−Rhamnolipid Complexes

This study investigated the formation and plant uptake of lipophilic metal-rhamnolipid complexes. Monorhamnosyl and dirhamnosyl rhamnolipids formed lipophilic complexes with copper (Cu), manganese (Mn), and zinc (Zn). Rhamnolipids significantly increased Zn absorption by Brassica napus var. Pinnacle roots in (65)Zn-spiked ice-cold solutions, compared with ZnSO4 alone. Therefore, rhamnolipid appeared to facilitate Zn absorption via a nonmetabolically mediated pathway. Synchrotron XRF and XAS showed that Zn was present in roots as Zn-phytate-like compounds when roots were treated with Zn-free solutions, ZnSO4, or Zn-EDTA. With rhamnolipid application, Zn was predominantly found in roots as the Zn-rhamnolipid complex. When applied to a calcareous soil, rhamnolipids increased dry matter production and Zn concentrations in durum (Triticum durum L. cv. Balcali-2000) and bread wheat (Triticum aestivum L. cv. BDME-10) shoots. Rhamnolipids either increased total plant uptake of Zn from the soil or increased Zn translocation by reducing the prevalence of insoluble Zn-phytate-like compounds in roots.

Brain targeting using novel lipid nanovectors

The present study shows the potential of novel nanovectors for the delivery of lipophilic radionuclides and therapeutic molecules to the brain. Lipid nanocapsules (LNC) inhibiting the P-gp pump efflux, were conjugated to OX26 monoclonal antibodies (OX26 MAb) and Fab' fragments. The OX26 MAb is directed against the transferrin receptor (TfR) highly expressed on the cerebral endothelium. The specific association of immunonanocapsules to rat brain capillary endothelial cells was demonstrated. Biodistribution of immunonanocapsules, labeled with a 188Re lipophilic complex, was determined in healthy rats. At 24 h post-injection, the brain concentrations of Fab'-immunonanocapsules and OX26-immunonanocapsules were, respectively, 1.5 and 2-fold higher than non-targeted nanocapsules. In addition, Fab' fragments helped prolong the vascular residence time of the nanovectors but their affinity to TfR was lower than whole antibodies. The ability of immunonanocapsules to specifically target cerebral tissues in addition to the promising features of LNC is of importance to the field of nanomedicine.

Transport of lipophilic ligands through permeation liquid membrane in relation to natural water analysis

Trace metal ions can exist in many chemical forms, such as free metal, labile and liposoluble metal complexes in natural waters. Although, free metal ions are well known to be bioavailable, liposoluble species may also be potentially bioavailable and toxic. For understanding the metal uptake and toxicity to microorganisms, analytical tools are required to measure the various metal species under natural water conditions. Permeation liquid membrane (PLM) devices, comprising of 1, 10 dicecyl diaza 18 crown ether 6 and lauric acid in phenylhexane–toluene mixture, were demonstrated to be well suited for the trace metal speciation, in particular, for the free Cu(II), Pb(II) and Cd(II) concentration measurements in natural waters. In the presence of both free metal ions and lipophilic complexes, both these species will be transported across the membrane. In order to evaluate the contribution of the lipophilic species in the measured flux, the concentration of the lipophilic species must be determined. In this paper, transport characteristics of 8-hydroxyquinoline (HQ, also known as oxine) through a flat sheet PLM comprising a mixture of toluene/phenylhexane has been studied to obtain information on the permeability. HQ was chosen as model organic compound because its metal complexations are well known and it forms neutral lipophilic complex with Cu(II). Copper-oxine is used as a pesticide and may be present in natural waters. Important parameters such as diffusion coefficient in the membrane, D m, partition coefficient, K p, between the solution and the membrane, and permeability coefficient, P, have been evaluated by studying the effect of pH and membrane thickness on HQ transport. The results showed that the neutral HQ species is transported efficiently across the membrane and that the charged protonated species are not transported. Values of D m = 3.0 × 10 −7 cm 2 s −1 and P = 2.47 × 10 −3 cm s −1 were found. The partition coefficient, K p, of HQ in phenylhexane/toluene mixture and toluene were also determined using the classical liquid/liquid extraction method for comparison. The results revealed that partition coefficient in toluene was higher than that in phenylhexane/toluene mixtures. However, the two values obtained for K p were comparable as expected.

Synthesis and biodistribution of two novel 99mTc nitrido dithiocarbamate complexes containing heterocyclic linkage as potential brain perfusion imaging agents

In the present study, two novel 99mTc nitrido dithiocarbamate complexes containing heterocyclic linkage, the bis(N-2-(1-piperidyl)ethyl dithiocarbamato) nitrido technetium-99m complex 99mTcN(PPEDTC)2 and bis(N-2-(1-pyrrolidino)ethyl dithiocarbamato) nitrido technetium-99m complex 99mTcN(PREDTC)2 have been synthesized by the reduction of 99mTcO4− into [99mTcN]2+ with stannous chloride in the presence of succinic dihydrazide and propylenediamine tetraacetic acid, followed by the addition of the corresponding dithiocarbamate ligands. The radiochemical purity of the complexes were over 90% as measured by thin layer chromatography (TLC). In vitro studies showed that the complexes possessed good stability. Their partition coefficients indicated that they were lipophilic complexes. Biodistribution in mice showed that the 99mTcN(PPEDTC)2 complex accumulated in brain with high uptake and good retention. As compared with the 99mTcN(PREDTC)2 complex, the former showed much higher brain uptake than the latter.

Synthesis and biodistribution of 99mTcN-isopentyl xanthate as a potential myocardial perfusion imaging agent

A novel 99mTc nitrido xanthate complex 99mTcN(IPEXT)2 (IPEXT: isopentyl xanthate) has been synthesized by the reduction of 99mTcO4− into [99mTcN]2+ with stannous chloride in the presence of succinic dihydrazide and propylenediamine tetraacetic acid, followed by the addition of the corresponding xanthate ligand. The radiochemical purity of the complex was over 90% as measured by thin layer chromatography (TLC). No decomposition of the complex at room temperature was observed over a period of 6 hours. Its partition coefficient indicated that it was a lipophilic complex. The electrophoresis results showed the complex was neutral. Biodistribution in mice showed that the 99mTcN(IPEXT)2 complex accumulated in the heart with high uptake. The heart uptake (%IDg) was 8.00% at 5-minute post-injection, but the heart/lung, heart/liver and heart/blood ratios were not high, thereby, restricting the use of the complex as a good myocardial imaging agent.