Comparison of the efficacy of 177Lu-EDTMP, 177Lu-DOTMP and 188Re-HEDP towards bone osteosarcoma: an in vitro study

Among the radiopharmaceuticals harnessed for palliation of bone pain in osseous metastases patients, ¹⁷⁷Lu labeled phosphonates such as EDTMP (Ethylene diamine tetramethylene phosphonic acid) as well as DOTMP (1,4,7,10-tetraaza-cyclo-dodecane-1,4,7,10 tetraethylene phosphonic acid) and ¹⁸⁸Re-labeled HEDP (1,1-hydroxyethylene diphosphonic acid) seem to be the most favorable for treatment of small and medium/large size bone lesions, respectively. A comparative assessment of ¹⁷⁷Lu-EDTMP, ¹⁷⁷Lu-DOTMP and ¹⁸⁸Re-HEDP in osteosarcoma tumor cell line was carried out to evaluate their relative efficacy. It was found that ¹⁸⁸Re-HEDP is more potent in induction of cell toxicity and apoptosis compared to the ¹⁷⁷Lu-EDTMP and ¹⁷⁷Lu-DOTMP, thus ¹⁸⁸Re-HEDP might have great clinical significance.

     

Preparation of radioiodinated ritodrine as a potential agent for lung imaging

Ritodrine (a beta-2 adrenergic receptor agonist) was successfully labeled with ¹²⁵I via direct electrophilic substitution reaction at ambient temperature. ¹²⁵I-ritodrine was obtained with a maximum labeling yield of 97 ± 0.163 % and in vitro stability up to 24 h. Biodistribution studies showed that maximum in vivo uptake of ¹²⁵I-ritodrine in lungs was 20.4 ± 0.22 % injected activity/g tissue at 1 h post-injection, whereas the clearance from mice appeared to proceed mainly via the renal pathway. ¹²⁵I-ritodrine is not a blood product and so it is more safe than the currently available ^99mTc-MAA, and its lung uptake is higher than that of the recently discovered ^99mTc(CO)₅I and ^99mTc-DHPM. As a conclusion, radioiodinated ritodrine could be used as a novel radiopharmaceutical for lung perfusion scan safer than the currently available ^99mTc-MAA and more potential than the recently discovered ^99mTc(CO)₅I and ^99mTc-DHPM.     

Preparation and biological evaluation of Tc-CO-MIBI as myocardial perfusion imaging agent

^99mTc-Sestamibi has been playing an important role in the cardiac imaging for the last decades. Previously, we reported that [^99mTc(CO)₃(MIBI)₃]⁺ demonstrated a significant location in myocardium with a lower liver uptake as compared with ^99mTc-Sestamibi. In this work, we found that new [^99mTc(CO)₂(MIBI)₄]⁺ could be prepared with high radiochemical purity. The inter-transformations between [^99mTc(CO)₃(H₂O)(MIBI)₂]⁺, [^99mTc(CO)₃(MIBI)₃]⁺, and [^99mTc(CO)₂(MIBI)₄]⁺ were investigated and biodistribution was performed to evaluate the [^99mTc(CO)₂(MIBI)₄]⁺ as a myocardial perfusion imaging agent. The results showed that one more CO was replaced by MIBI slowing down the pharmacokinetics. The structure characterization was performed on their corresponding rhenium complexes, and the results indicated that there were differences between ^99mTc-CO-MIBI and Re-CO-MIBI in preparation and hydrophobic characteristics.     

A bisphosphonate monoamide analogue of DOTA: a potential agent for bone targeting

A new macrocyclic DOTA-like ligand (BPAMD) for bone imaging and therapy containing a monoamide bis(phosphonic acid) bone-seeking group was designed and synthesized. Its lanthanide(III) complexes were prepared and characterized by 1H and 31P NMR spectroscopy. The Gd(III)-BPAMD complex was investigated in detail by 1H and 17O relaxometric studies to inspect parameters relevant for its potential application as an MRI contrast agent. Sorption experiments were conducted with Gd(III) and Tb(III) complexes using hydroxyapatite (HA) as a model of bone surface. Very effective uptake of the Gd-BPAMD complex by the HA surface was observed in NMR experiments. Radiochemical studies with the (160Tb-BPAMD)-HA system proved the sorption to be remarkably fast and strong on one hand and fully reversible on the other hand. The strong (Gd-BPAMD)-HA interaction was also supported by 1H NMRD measurements in the presence of a hydroxyapatite slurry, which showed an increase of the rotational correlation time upon adsorption of the complex on the HA surface, resulting in a significant relaxivity enhancement. The amide-bis(phosphonate) moiety is the only factor responsible for the binding of the complex to HA.     

Synthesis,radiolabeling and biological distribution of a new dioxime derivative as a potential tumor imaging agent

A novel dioxime derivative (2E,2′E,3E,3′E)-3,3′-(pyrimidine-4,5-diylbis(azanylylidene))bis(butan-2-one)dioxime was synthesized with a yield of 65%. IR, elemental analysis, mass spectroscopy and ¹H-NMR were used to characterize the structure of the synthesized compound. ^99mTc-dioxime was radio-synthesized with a high radiochemical yield of 97.8 ± 0.5% and in vitro stability of 6 h under the optimum conditions. The preclinical evaluation of ^99mTc-dioxime in solid tumor-bearing mice showed high accumulation in solid tumor cells with a high Target/Non-Target ratio of 5.14 at 30 min post-injection. This study suggests that ^99mTc-dioxime derivative is a promising candidate as a new ^99mTc-based tumor-imaging agent after further preclinical studies.     

Synthesis and biodistribution of the 99m TcN-DMSA complex as a potential bone imaging agent

In this study, the preparation of the 99m TcN complex of DMSA (dimercaptosuccinicacid) was carried out as a freeze-dried formulation, through a simple procedureinvolving the initial of 99m TcO 4 – with succinic dihydrazide in thepresence of stannous chloride as reducing agent, followed by the additionof the ligand DMSA to afford the final product. The radiochemical purity ofthe 99m TcN-DMSA complex was over 90% determined by thin layer chromatography.It was stable over 8 hours at room temperature. Its partition coefficientindicated that it was a good hydrophilic complex. Biodistribution in miceshowed that the 99m TcN-DMSA complex was accumulated in bone with high uptakeand good retention, suggesting it would be potentially useful as a bone imagingagent containing the [ 99m TcN] 2+ core. The biodistribution comparison inmice of the 99m TcN-DMSA complex and the 99m Tc-DMSA complex indicate thatthe presence of the 99m Tc nitrido group significantly alters the biologicalproperties of the 99m Tc complex.     

Synthesis and biological evaluation of novel technetium-99m-labeled HYNIC-d-glucose as a potential tumor imaging agent

A conjugate of 6-hydrazinopyridine-3-carboxylic acid (HYNIC) with the d-Glucosamine Hydrochloride (DG) was synthesized though a multiple-step reaction. HYNIC-DG could be labeled successfully and efficiently with ^99mTc using N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine (tricine) and ethylenediamine-N,N′-diacetic acid (EDDA) or tricine and triphenylphosphine-3,3′,3″-trisulfonic acid trisodium salt (TPPTS) as co-ligands to form two ^99mTc-HYNIC-DG complexes ^99mTc-(t/E)HYNIC-DG and ^99mTc-(t/T)HYNIC-DG in high yields (>95 %). The partition coefficient and electrophoresis results indicated they were very hydrophilic and electronegative. The biodistribution studies of two ^99mTc-HYNIC-DG complexes in Kunming mice bearing S 180 tumor showed that ^99mTc-(t/T)HYNIC-DG has more favorable characteristics than ^99mTc-(t/E)HYNIC-DG. High tumor uptake, low or negligible accumulation in non-target organs, and good retention, suggesting ^99mTc-(t/T)HYNIC-DG would be a novel potential tumor imaging agent.     

Preparation and preliminary bioevaluation of 68Ga-oxine in lipiodol as a potential liver imaging agent

Lipiodol functions as an embolizing agent for trans-arterial embolization and is used to deliver localized doses of chemotherapeutic drugs as well as ionizing radiation to cancerous tissue of the liver. Therefore, an attempt was made to prepare ⁶⁸Ga-labeled lipiodol, which may have potential as a PET radiotracer for imaging of liver cancer. ⁶⁸Ga-labeled lipiodol was prepared by a two-step procedure involving formation of highly lipophilic ⁶⁸Ga-oxine complex followed by its dispersion in lipiodol. Preliminary biological evaluation in normal Wistar rats revealed satisfactory hepatic retention with insignificant uptake in any other major organ/tissue indicating promising potential of the agent.

     

Preparation and biodistribution study of technetium-99m-labeled quercetin as a potential radical scavenging agent

Free radicals and oxidative stress are the primary causes of several chronic diseases such as cancer and heart disease. Quercetin is a natural compound with potent antioxidant activity. We have prepared and evaluated technetium-99m (^99mTc)-labeled quercetin as a potential radical scavenging radiotracer. A ^99mTc-quercetin complex was prepared using quercetin, SnCl₂ and Na^99mTcO₄ in a buffered solution over 30 min. The participation coefficient was measured in octanol and queues solutions. The stability was determined in phosphate buffered saline and serum. The biodistribution in normal mice was evaluated at 0.5, 2, 6 and 24 h post-injection. The radiochemical purity (>99%) was determined by thin layer chromatography (TLC) in normal saline solution as the mobile phase. It has a log P of 0.204. It was mainly cleared by the kidneys and showed negligible brain uptake at four time points measured post-injection. The pharmacological properties of quercetin, mainly its free radical scavenging, may potentially cat as a radiopharmaceutical agent for radical-targeted imaging of tissue with high levels of reactive oxygen species.     

一种用于肿瘤治疗的高光热转换效率和高稳定性的光热剂

基于香豆素荧光团设计合成了一种光热剂(ECEI),其光热转换效率可达 85.78%。此外,冷热循环的实验结果表明,ECEI 具有良好的光稳定性。即使在线粒体膜电位受损的情况下,ECEI 也能有效靶向线粒体,在激光照射下诱导癌细胞死亡。这使 ECEI能够最大程度地破坏线粒体,从而抑制肿瘤细胞的繁殖。对小鼠肿瘤照射 1次后,小鼠肿瘤在 10 d内逐渐消失,这表明ECEI具有良好的肿瘤抑制效果。     

一种用于肿瘤治疗的高光热转换效率和高稳定性的光热剂

基于香豆素荧光团设计合成了一种光热剂(ECEI),其光热转换效率可达 85.78%。此外,冷热循环的实验结果表明,ECEI 具有良好的光稳定性。即使在线粒体膜电位受损的情况下,ECEI 也能有效靶向线粒体,在激光照射下诱导癌细胞死亡。这使 ECEI能够最大程度地破坏线粒体,从而抑制肿瘤细胞的繁殖。对小鼠肿瘤照射 1次后,小鼠肿瘤在 10 d内逐渐消失,这表明ECEI具有良好的肿瘤抑制效果。     

Synthesis and biological evaluation of a novel <Superscript>99m</Superscript>Tc complex of HYNIC-conjugated aminomethylenediphosphonate as a potential bone imaging agent

A conjugate of 6-hydrazinopyridine-3-carboxylic acid (HYNIC) with aminomethylenediphosphonic acid (AMDP) was synthesized through a multiple-step reaction. HYNIC–AMDP could be labeled easily and efficiently with ^99mTc using N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine) as coligand to form the ^99mTc–HYNIC–AMDP complex in high yield (> 95%). Its partition coefficient indicated that it was a good hydrophilic complex. The biodistribution studies of ^99mTc–HYNIC–AMDP in normal ICR mice showed that this complex had high bone uptake and low or negligible accumulation in non-target organs. As compared with ^99mTc–MDP, ^99mTc–HYNIC–AMDP had a higher bone uptake and the ratios of bone/blood and bone/muscle at early time after injection, suggesting that it could be potentially useful for bone imaging at an earlier time after injection according to further investigations of the biological behavior of this complex.     

The potential of tetrandrine as a protective agent for ischemic stroke

Stroke is one of the leading causes of mortality, with a high incidence of severe morbidity in survivors. The treatment to minimize tissue injury after stroke is still unsatisfactory and it is mandatory to develop effective treatment strategies for stroke. The pathophysiology of ischemic stroke is complex and involves many processes including energy failure, loss of ion homeostasis, increased intracellular calcium level, platelet aggregation, production of reactive oxygen species, disruption of blood brain barrier, and inflammation and leukocyte infiltration, etc. Tetrandrine, a bisbenzylisoquinoline alkaloid, has many pharmacologic effects including anti-inflammatory and cytoprotective effects. In addition, tetrandrine has been found to protect the liver, heart, small bowel and brain from ischemia/reperfusion injury. It is a calcium channel blocker, and can inhibit lipid peroxidation, reduce generation of reactive oxygen species, suppress the production of cytokines and inflammatory mediators, inhibit neutrophil recruitment and platelet aggregation, which are all devastating factors during ischemia/reperfusion injury of the brain. Because tetrandrine can counteract these important pathophysiological processes of ischemic stroke, it has the potential to be a protective agent for ischemic stroke.