Preparation and biological study of [68]Ga-DOTA-alendronate

Objective[s]: In line with previous research on the development of conjugated bisphosphonate ligands as new bone-avid agents, in this study, DOTA-conjugated alendronate [DOTA-ALN] was synthesized and evaluated after labeling with gallium-68 [[68]Ga]

Methods: DOTA-ALN was synthesized and characterized, followed by [68]Ga-DOTA-ALN preparation, using DOTA-ALN and [68]GaCl[3] [pH: 4-5] at 92-95°C for 10 min. Stability tests, hydroxyapatite assay, partition coefficient calculation, biodistribution studies, and imaging were performed on the developed agent in normal rats

Results: The complex was prepared with high radiochemical purity [>99% as depicted by radio thin-layer chromatography; specific activity: 310-320 GBq/mmol] after solid phase purification and was stabilized for up to 90 min with a logP value of -2.91. Maximum ligand binding [65%] was observed in the presence of 50 mg of hydroxyapatite; a major portion of the activity was excreted through the kidneys. With the exception of excretory organs, gastrointestinal tract organs, including the liver, intestine, and colon, showed significant uptake; however, the bone uptake was low [<1%] at 30 min after the injection. The data were also confirmed by sequential imaging at 30-90 min following the intravenous injection

Conclusion: The high solubility and anionic properties of the complex led to major renal excretion and low hydroxyapatite uptake; therefore, the complex failed to demonstrate bone imaging behaviors

Development of [111]In-labeled porphyrins for SPECT imaging

The aim of this research was the development of [111]In-labeled porphyrins as possible radiopharmaceuticals for the imaging of tumors. Ligands, 5, 10, 15, 20-tetrakis [3, 5-dihydroxyphenyl] porphyrin] [TDHPP], 5, 10, 15, 20-tetrakis [4-hydroxyphenyl] porphyrin [THPP] and 5, 10, 15, 20-tetrakis [3,4-dimethoxyphenyl] porphyrin] [TDMPP] were labeled with [111]InCl3 [produced from proton bombardment of natCd target] in 60 min at 80[degree sign]C. Quality control of labeled compounds was performed via RTLC and HPLC followed by stability studies in final formulation and presence of human serum at 37[degree sign]C for 48 h as well as partition coefficient determination. The biodistribution studies performed using tissue dissection and SPECT imaging up to 24h. The complexes were prepared with >99% radiochemical purity [HPLC and RTLC], high stability in 48h. Partition coefficients [calculated as log P] for [111]In-TDHPP, [111]In-THPP and [111]In-TDMPP were 0.88, 0.8 and 1.63 respectively. Due to urinary excretion with fast clearance for [111]In-TDMPP, this complex is probably a suitable candidate for considering as a possible tumor imaging agent

Production and quality control of [67Ga]-DOTA-trastuzumab for radioimmunoscintigraphy

Breast cancer radioimmunoscintigraphy targeting HER2/neu expression is a growing field of work in nuclear medicine research. In this study, trastuzumab was successively labeled with [[67]Ga] GaCl3 after conjugation with DOTA-NHS-ester. The conjugates were purified by molecular filtration, the average number of DOTA conjugated per mAb was calculated and total concentration was determined by spectrophotometric method. DOTA-Trastuzumab was labeled with [67]Ga. Radiochemical purity, integrity of protein after radiolabeling and stability of [67]Ga-DOTA-Trastuzumab were determined followed by biodistribution studies in wild-type rats [30 +/- 5.5 micro Ci, 2, 4 and 24 h p.i.]. The radioimmunoconjugate was prepared with a radiochemical purity of higher than 95% [RTLC]. The average chelate to antibody ratio [c/a] for the conjugate used in this study was 5.8:1. The final compound was stable in presence of PBS at 37[degree sign]C and room temperature. The sample was showed to have similar patterns of migration in the gel electrophoresis similar to the native protein. The accumulation of the radiolabeled antibody in liver, spleen, kidney, heart and other tissues demonstrates. [67]Ga-DOTA-Trastuzumab was prepared as a surrogate for important clinically applicable radionuclides used in SPECT and PET including In-111 and Cu-64 as a model of radiolabeling. It is also a potential compound for molecular imaging of SPECT for diagnosis and treatment studies and follow-up of HER2 expression in oncology

Production, quality control and biological evaluation of [153] Sm-TTHMP as a possible bone palliation agent

Various bone palliative therapeutic agents have been developed and widely used for bone metastasis such as [153]Sm-EDTMP. In this study, production, quality control and biodistribution studies of a newly developed therapeutic compound have been presented followed by imaging studies in wild-type rodents. [153]Sm-TTHMP was prepared starting from [153]Sm-SmCl[3], prepared by neutron activation of an enriched [152]Sm sample [purity >98%], and in-house synthesized TTHMP in 1h at 25[degree sign] C followed by stability tests, partition coefficient determination and biodistribution studies of in wild-type rodents using scarification and SPECT imaging. The radiolabled Sm complex was prepared in high radiochemical purity [>99%, ITLC] and specific activity of 278 GBq/mmol and demonstrated significant ability at 4, 25 and 37 [degree sign] C [in presence of human serum]. Initial biodistribution data showed significant bone accumulation of the tracer in 48h. [153]Sm-TTHMP can be a potential candidate for bone pain palliation therapy in skeletal metastases, although further biological studies in other mammals is still needed

Evaluation of [[67]Ga] citrate in the detection of various microorganism infections in animal models

Gallium-67 citrate has been known as a good infection agent in nuclear medicine for decades. In this work the value of [67]Ga-citrate has been investigated in infected animal models using SPECT imaging at optimized/standardized conditions. The bacterial [Staphylococcus aureus; S.a. and Escherichia coli; E.c.] and fungal [Candidae albicans; C.a.] species from standard sources were cultured according to the standard procedures and wild-type NMRI rats were inoculated by the injection of 5x10[7] microorganisms [MO] into their thighs and animals incubated for infection site formation for 2 and 3 days followed by iv injection of freshly prepared [67]Ga-citrate [45-50 micro Ci] and SPECT imaging performed at 2, 4 and 24 hours post injection in parallel with control groups. In S.a.-infected rats [67]Ga-citrate demonstrated hot spot foci at all time intervals esp. 24h post injections in contrast with normal animal scans. In case of C.a., the infected animals also demonstrated significant accumulation foci being most significant after 24h. In E.c.-infected animals however weak positive scans were obtained even after 24 hours. Our animal models developed for the evaluation of new infection-targeting agents were successfully positive using [67]Ga scan. These models can also be used in the evaluation of newly developed antibiotics in animal models for in vivo studies. The efficacy of [67]Ga-scan in our microorganism infection models can be summarized as S.A.>C.a.>E.c.