Preclinical Evaluation of 68Ga-MAA from Commercial Available 99mTc-MAA Kit.

99mTc-Macroaggregated Albumin (99mTc-MAA) has been used as a perfusion agent. This study described development of the 68Ga-MAA via commercially available kits from Pars-Isotopes Company as a 99mTc-MAA kit. 68Ge/68Ga generator was eluted with suprapure HCl (0.6 M, 6 mL) in 0.5 mL fractions. The two fractions with the highest 68GaCl3 activity were generally used for labeling purposes. After labeling, the final product was centrifuged 2 times to purify the solution. Five rats were sacrificed at each exact time interval (from 15 min to 2 h post injection) and the percentage of injected dose per gram (%ID/g) of each organ was measured by direct counting from 11 harvested organs of rats. The RTLC showed that labeling yields before centrifuges were 90% and 95% for Pars-Isotopes and GE kits, respectively and after centrifuges, they became 100%. The microscopic size examination showed a shift in the particle sizes post centrifuges and the biodistribution data revealed the efficiency and benefits of centrifuges in terms of preventing the of liver and bone marrow uptakes especially for Pars-Isotopes kits. Our results showed that after centrifuges of the final product, the lung uptakes increased from 89% to more than 97% of %ID/g after 5 min post injections. The whole procedure took less than 25 min from elution to the final product. Since 99mTc-MAA remained longer than 68Ga-MAA in the lung and 68Ga-MAA showed better image qualities, using 68Ga-MAA is recommended.

Preparation and Evaluation of (68)Ga-ECC as a PET Renal Imaging Agent.

PURPOSE: Development of a gallium-68-labeled renal tracer can be a good substitute for Tc-99m, a known SPECT tracer. In this study, effort was made to develop (68)Ga-ethylenecysteamine cysteine ((68)Ga-ECC). METHODS: Ga-ECC was prepared using generator-based (68)GaCl3 and ethylenecysteamine cysteine (ECC) at optimized conditions. Stability of the complex was checked in human serum followed by partition coefficient determination of the tracer. The biodistribution of the tracer in rats was studied using tissue counting and PET/CT imaging up to 120 min. RESULTS: Ga-ECC was prepared at optimized conditions in 15 min at 90 °C (radiochemical purity ≈97 ± 0.88 % ITLC, >99 % HPLC, specific activity: 210 ± 5 GBq/mM). (68)Ga-ECC was a water-soluble complex based on partition coefficient data (log P; -1.378) and was stable in the presence of human serum for 2 h at 37 °C. The biodistribution of the tracer demonstrated high kidney excretion of the tracer in 10-20 min. The SUVmax ratios of the liver to left kidney were 0.38 and 0.39 for 30 and 90 min, respectively, indicating high kidney uptake. CONCLUSION: Initial biodistribution results showed significant kidney and urinary excretion of the tracer comparable to that of the homologous (99m)Tc compound. The complex could be a possible PET kidney imaging agent with a fast imaging time.

Optimized production and quality control of (68)Ga-EDTMP for small clinical trials.

OBJECTIVE: Optimized production and quality control of gallium-68 labeled ethylenediamine tetramethylene phosphonate ((68)Ga-EDTMP) as an efficient PET radiotracer for bone scans have been presented. METHODS: Efforts have been made to present a fast, efficient, cost-effective and facile protocol for (68)Ga-EDTMP productions for clinical trials. (68)Ga-EDTMP was prepared using generator-based (68)GaCl3 and EDTMP at optimized conditions for time, temperature, ligand amount, gallium content followed by proper formulation. The biodistribution of the tracer in rats was studied using tissue counting and PET/CT imaging up to 155 min. RESULTS: (68)Ga-EDTMP was prepared at optimized conditions in 5-10 min at 50-60 °C (radiochemical purity ≈99 ± 0.88 % ITLC, >99 % HPLC, specific activity: 15-18 GBq/mM). The biodistribution of the tracer demonstrated high bone uptake of the tracer in 10-20 min while yielding the best images in 2 h. CONCLUSION: The whole production and quality control of (68)Ga-EDTMP including labeling, purification, HPLC analysis, sterilization and LAL test took 18-20 min with significant specific activity for administration to limited number of patients in a PET center.

Development of (177)Lu-phytate Complex for Radiosynovectomy.

OBJECTIVE(S): In this work a new possible agent for radiosynovectomy has been targeted for articular pain palliation. MATERIALS AND METHODS: Lu-177 of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu2O3 sample with thermal neutron flux of 4 × 10(13) n.cm(-2).s(-1). The product was converted into chloride form which was further used for labeling of (177)Lu-phytate complex and checked using ITLC (MeOH: H2O: acetic acid, 4: 4: 2, as mobile phase). The complex stability and viscosity were checked in the final solution up to seven days. The prepared complex solution (100 µCi/100 µl) was injected intra-articularly to male rat knee joint. Leakage of radioactivity from injection site and its distribution in organs were investigated up to seven days. RESULTS: The complex was successfully prepared with high radiochemical purity (>99.9 %). Approximately, the whole injected dose has remained in injection site seven days after injection. CONCLUSION: The complex was proved to be a feasible agent for cavital radiotherapy in oncology and rheumatology.

Preparation and biological evaluation of [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide for somatostatin receptor-positive tumor imaging.

Somatostatin-derived analogues play an important role in the diagnosis and treatment of neuroendocrine tumors. The aim of this study was to evaluate a new somatostatin analogue designed for labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), ß-(3-benzothienyl)-Ala (BzThi(3))]-octreotide ([HYNIC]-BOC), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Synthesis was performed on a solid phase using a standard Fmoc strategy. The HYNIC-peptide conjugate was radiolabeled with (99m)Tc and characterized by ITLC and high-performance liquid chromatography (HPLC). In vitro studies were carried out in sstr2 expressing AR4-2J cell lines. In vivo distribution studies were performed in rats bearing the AR4-2J tumor. The radiolabeled complex could be prepared at high-specific activities and >95% radiochemical yield as determined by HPLC. The peptide conjugate showed high-affinity binding for sstr2. The radioligand showed high and specific internalization into AR4-2J cells (18.19%±0.21% at 4 hours). In vivo distribution studies in rats bearing tumor have shown a receptor-specific uptake of radioactivity in somatostatin receptor-positive organs. After 4 hours, uptake in the AR4-2J tumor was 1.71%±0.36% injected dose per gram tissue (%ID/g). These data show that [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide is a specific radioligand for the somatostatin receptor-positive tumors and is a suitable candidate for clinical studies.

Comparison of (99m)Tc-labeled PR81 and its F(ab')2 fragments as radioimmunoscintigraphy agents for breast cancer imaging.

OBJECTIVE: We digested anti-MUC1 monoclonal antibody PR81 to produce F(ab')2 fragments. A comparison was performed between the two radiolabeled PR81 and F(ab')2 fragments for breast tumor imaging in a mouse model. METHODS: The optimum conditions for pepsin digestion of PR81 were investigated in terms of enzymes: antibody ratio, digestion time duration and preserved immunoreactivity of the produced fragments. The F(ab')2 fragments were labeled with Technetium-99m using HYNIC as a chelator and tricine as a co-ligand. The immunoreactivity of the complexes was assessed by radioimmunoassay using MCF7 cells. Biodistribution and imaging studies were performed in female BALB/c mice with breast tumor xenograft at 4, 8 and 24 h post-administration. The PR81 was labeled with technetium-99m in the same way for comparison. RESULTS: The optimum time duration for PR81 digestion was found to be 28 h at an enzyme:antibody weight ratio of 1:20 that resulted in 95.2 ± 4.7% purity. The labeling of intact PR81 and its F(ab')2 fragments were 87.6 ± 4.2 and 76.1 ± 3.3% after 1 h, respectively (p value <0.05). The percentage of immunoreactivity of F(ab')2 fragments and intact PR81 were 75.4 ± 2.1% and 85.7 ± 2.9%, respectively (p value <0.05). The biodistribution and imaging studies demonstrated localization of the fragments at 4 h post-administration with high sensitivity and specificity. CONCLUSION: The results showed that F(ab')2 fragment of PR81 is more suitable than intact PR81 for safer and more rapid detection of human breast cancer.

Development of (166)Ho-phytate Complex for Radiosynovectomy.

BACKGROUND: (66)Ho-chloride was obtained by bombardment of natural Ho(NO3)3 dissolved in acidic media using thermal neutron flux (4-5 × 10(13) n.cm(-2).s(-1)). METHODS: (166)Ho-holmium chloride (185 MBq) was used successfully for preparation of (166)Ho-phytate complex with high radiochemical purity (>99.9 %, ITLC, MeOH: H2O: acetic acid, 4: 4: 2, as mobile phase). The complex stability and viscosity were checked in the final solution up to 2 days. The prepared complex solution (60 µCi/100 µl) was injected intraarticularly to male rat knee joints. Leakage of radioactivity from the injection site and its distribution in organs were investigated up to 2 days. RESULTS: Approximately all of the injected dose had remained in the injection site 2 days after injection. CONCLUSION: The complex was proved to be a feasible agent for cavital radiotherapy in oncology and rheumatology.

Clinical evaluation of antimicrobial peptide [(99m)Tc/Tricine/HYNIC(0)]ubiquicidin 29-41 as a human-specific infection imaging agent.

INTRODUCTION: Ubiquicidin (UBI) 29-41 is a cationic synthetic antimicrobial peptide fragment that binds preferentially with the anionic microbial cell membrane at the site of infection. This study was conducted to evaluate the potentiality of [(99m)Tc/Tricine/HYNIC(0)]UBI 29-41 prepared from lyophilized kits as an infection imaging agent in humans. METHODS: Seven patients (5 males and 2 females; mean age=55 years; age range=35-75 years) with suspected bone or soft-tissue infections participated in this study. [(99m)Tc/Tricine/HYNIC]UBI 29-41, corresponding to activity in the range 555-740 MBq added to 40 mug of peptide obtained from instant freeze-dried kit formulations with radiochemical purities >95%, was injected intravenously. A 45-min dynamic study was followed by spot views of the suspected region of infection (target) and a corresponding normal area (nontarget). Whole-body anterior and posterior images were also acquired at 30, 60 and 120 min after injection. True- or false-positive or true- or false-negative images were interpreted upon bacterial culture, radiography, clinical tests and bone scanning. RESULTS: The biodistribution of [(99m)Tc/Tricine/HYNIC]UBI 29-41 in patients showed rapid accumulation of activity in the kidneys in the first 30 min after injection that gradually declined and accumulated in the urinary bladder. There were positive findings in five studies and negative findings in two. Findings were subsequently confirmed to be true positive or negative. Images showed minimal accumulation in nontarget tissues, with an average target/nontarget ratio of 2.10+/-0.33 in positive lesions at 30 min. CONCLUSION: Given its favorable clinical characteristics, [(99m)Tc/Tricine/HYNIC]UBI 29-41 shows promise as a tracer for infection imaging that allows early diagnosis (30 min) of infection.

Preclinical evaluation of [99mTc/EDDA/tricine/HYNIC0, 1-Nal3, Thr8]-octreotide as a new analogue in the detection of somatostatin-receptor-positive tumors.

PURPOSE: Radiolabeled somatostatin analogues are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin-receptor-positive tumors. The aim of this study was to evaluate a new somatostatin analogue designed for the labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), 1-Nal(3), Thr(8)]-octreotide ([HYNIC]-NATE), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. METHODS: Synthesis was preformed on a solid phase using a standard Fmoc strategy. Labeling with (99m)Tc was performed at 100 degrees C for 10 min using SnCl(2) as a reductant. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate affinity was determined in AR4-2J cell membranes. The internalization and externalization rates were studied in sstr(2)-expressing AR4-2J cells. Biodistribution of radiopeptide was studied in rats bearing the AR4-2J tumor. RESULTS: Radiolabeling was performed at high specific activities, and radiochemical purity was >95%. Peptide conjugate showed high affinity binding for sstr(2). The radioligand showed a moderate and specific internalization into AR4-2J cells (14.13+/-0.61% at 4 h). In animal biodistribution studies, a receptor-specific uptake of radioactivity was observed in somatostatin-receptor-positive organs. After 4 h, uptake in the AR4-2J tumor was 1.33+/-0.23%ID/g (percentage of injected dose per gram of tissue). CONCLUSION: These data show that [(99m)Tc/EDDA/tricine/HYNIC]-NATE is a specific radioligand for the somatostatin-receptor-positive tumors and is a suitable candidate for clinical studies.

Effects of religion and type of religious internalization on the mental health of Iranian adolescents.

This study was designed to assess the effects of religion and two types of religious internalization on the mental health of Iranian adolescents. High school students (82 Moslem and 37 Christian) were selected randomly from four high schools in Shiraz and completed the Religious Self-regulation Questionnaire and the General Health Questionnaire. Analysis showed that main effects of types of religious internalization measured on four subscales of the General Health Questionnaire were significant. Religion was significantly associated only with somatic symptoms. For other scales no main effects of religion, types of religious internalization, or their interactions were significant.

Intensity and prevalence of current fears among Iranian university students.

The intensity and prevalence of fears were assessed in Iranian university students by applying the Fear Survey Schedule for Children, II. Analysis indicated that the intensity and prevalence of fears varied by students' sex, field of study, and birthplace. Results are discussed in relation to previous findings, and a few recommendations together with some educational implications were noted.