Preclinical studies of [68]Ga-DOTATOC: biodistribution assessment in Syrian rats and evaluation of absorbed dose in human organs

Objective[s]: Gallium-68 DOTA-DPhe[1]-Tyr[3]-Octreotide [[68]Ga-DOTATOC] has been applied by several European centers for the treatment of a variety of human malignancies. Nevertheless, definitive dosimetric data are yet unavailable. According to the Society of Nuclear Medicine and Molecular Imaging, researchers are investigating the safety and efficacy of this radiotracer to meet Food and Drug Administration requirements. The aim of this study was to introduce the optimized procedure for [68]Ga-DOTATOC preparation, using a novel germanium-68 [[68]Ge]/[68]Ga generator in Iran and evaluate the absorbed doses in numerous organs with high accuracy

Methods: The optimized conditions for preparing the radiolabeled complex were determined via several experiments by changing the ligand concentration, pH, temperature and incubation time. Radiochemical purity of the complex was assessed, using high-performance liquid chromatography and instant thin-layer chromatography. The absorbed dose of human organs was evaluated, based on biodistribution studies on Syrian rats via Radiation Absorbed Dose Assessment Resource Method

Results: [68]Ga-DOTATOC was prepared with radiochemical purity of >98% and specific activity of 39.6 MBq/nmol. The complex demonstrated great stability at room temperature and in human serum at 37[degree]C at least two hours after preparation. Significant uptake was observed in somatostatin receptor-positive tissues such as pancreatic and adrenal tissues [12.83%ID/g and 0.91%ID/g, respectively]. Dose estimations in human organs showed that the pancreas, kidneys and adrenal glands received the maximum absorbed doses [0.105, 0.074 and 0.010 mGy/MBq, respectively]. Also, the effective absorbed dose was estimated at 0.026 mSv/MBq for [68]Ga-DOTATOC

Conclusion: The obtained results showed that [68]Ga-DOTATOC can be considered as an effective agent for clinical PET imaging in Iran

Production, biodistribution assessment and dosimetric evaluation of [177]Lu-TTHMP as a bone pain palliation agent

Objective[s]: recently, bone-avid radiopharmaceuticals have been shown to have potential benefits for the treatment of widespread bone metastases. Although 177Lutriethylene tetramine hexa methylene phosphonic acid [abbreviated as 177Lu- TTHMP], as an agent for bone pain palliation, has been evaluated in previous studies, there are large discrepancies between the obtained results. In this study, production, quality control, biodistribution, and dose evaluation of 177Lu-TTHMP have been investigated and compared with the previously reported data

Methods: TTHMP was synthesized and characterized, using spectroscopic methods. Radiochemical purity of the 177Lu-TTHMP complex was determined using instant thin-layer chromatography [ITLC] and high performance liquid chromatography [HPLC] methods. The complex was injected to wild-type rats and biodistribution was studied for 7 days. Preliminary dose evaluation was investigated based on biodistribution data in rats

Results: 177Lu was prepared with 2.6-3 GBq/mg specific activity and radionuclide purity of 99.98%. 177Lu-TTHMP was successfully prepared with high radiochemical purity [>99%]. The complex showed rapid bone uptake, while accumulation in other organs was insignificant. Dosimetric results showed that all tissues received almost insignificant absorbed doses in comparison with bone tissues

Conclusion: based on the obtained results, this radiopharmaceutical can be a good candidate for bone pain palliation therapy in skeletal metastases

Preparation and quality control of [177]Lu-chitosan for radiosynovectomy

Rheumatoid arthritis [RA] is the most common autoimmune disease, leading to the destruction of the joints and causing pain, disability, and immobility in the patients. Radiosynovectomy [RSV] has been applied as an effective treatment for the patients with resistant synovitis after failure of long-term pharmacotherapy and intra-articular steroid injection for more than 50 years. Several radiopharmaceuticals have been developed for RSV so far, but still development of new radiophamaceuticals is of crucial interest. In this research, the [177]Lu-chitosan complex [[177]Lu-CHITO] was introduced as a new agent for RSV. [177]Lu was produced by irradiation of a natural Lu2O3 target at a thermal neutron flux of approximately 4 x 10[13] n/cm[2]s. [177]Lu-CHITO was prepared in the diluted acetic acid solution. The radiochemical yield was checked by ITLC method. The biodistribution of the complex was investigated by intra-articular injection to rabbits' and rats' knee joints. The leakage of injected dose from the injection site in the rabbit organs was investigated using SPECT imaging up to 48 hours. [177]Lu was prepared with a specific activity of 2.6-3 GBq.mg[-1] and radionuclide purity of 99.98%. [177]Lu-CHITO was prepared successfully with high radiochemical purity [95%] and specific activity of 888 TBq/mmol. Both the biodistribution data in rats and SPECT imaging of the rabbit showed that there was no significant leakage of the injected activity even after 192 h. Considering all of the excellent features of the complex, this radiopharmaceutical can be used for effective management of synovial inflammation

Production and quality control of [166]Ho-chitosan for therapeutic applications

In this research, [[166]Ho]Holmium chitosan complex production is described in details, followed by determination of complex radiochemical purity, stability and biodistribution [after intra-articular injection] in wild-type male rats. Finally a Ho-166 based chitosan kit for ultimate radiosynovectomy as well as radiotherapy applications was developed. [166]Ho-chitosan complex was prepared using chitosan concentrations and [166]HoCl[3] followed by intra-articular injection and biodistribution studies in wild-type rats including and excluding injected knee. The [[166]Ho]Holmium chitosan complex was prepared with high radiochemical yield [>95%] in the optimized condition [35mg/3ml of chitosan in%1 AcOH, pH. 3, >98%, ITLC] was injected to wild-type rats followed by the biodistribution studies of the compound among the tissues excluding the injected knee data. Intra-articular injection of [[166]Ho]holmium chitosan complex to male wild-type rats and investigation of leakage of activity in the body showed that most of injected dose has remained in injection site 144 h after injection. Successful development and formulation of [166]Ho-chitosan kit is described. This kit has the potential for use in clinical setting namely for radiosynovectomy and cancer radiochemotherapy