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

Indium-111 maltolate complex as a cell labeling agent for SPECT imaging

Due to the cell labeling potentials of various metal-maltol complexes, the idea of developing a possible cell labeling imaging agent using single photon emission computed chromatography [SPECT] with [[m]ln]-maltolate complex has been investigated. [[IH]In] labeled 3-hydroxy-2-methyl-4H-pyran-4-onate [[m]In]-maltolate] was prepared using freshly prepared [[IH]In]InCl[3] and 3-hydroxy-2-methyl-4H-pyran-4-onate in a sodium salt form in 25 min at 45°C. Stability of the complex was checked in final formulation and human serum for 48 h. The partition coefficient was calculated for the compound followed by biodistribution and imaging studies. [[IU]In]-maltolate was successively used in the radiolabeling of red blood cells for diagnostic studies. The complex was prepared successfully [radiochemical purity: >98% ITLC, >98% HPLC specific activity: 15-17 GBq/mmol, log P=0.278]. The complex is mostly washed out from the circulation through kidneys in 24h. the cell labeling efficacy was significant at the time of experiment. [[In]ln]-maltolate can be an interesting cell imaging agent, due to stability and cell avidity of metal maltol complexes, however, further biodistribution studies in various cells as well as diagnostic protocols is necessary

Radiosynthesis and biological evaluation of [111]in-tris [8-hydroxy-2-methylquinoline] complex as a possible imaging agent

Due to the interesting pharmacological properties of radiolabeled metal oxine derivatives such as cell internalization, tumor avidity and antiproteosome activity, [111]In-tris[8-Hydroxy-2-methylquinoline] [[111]In-HMQ] was developed in this study. [111]In-HMQ was prepared using [111]InCl[3] and 8-Hydroxy-2-methylquinoline [HMQ] for 60 min at 100[degree sign] C [radiochemical purity: >99% ITLC, >99% HPLC, specific activity: 13-14 GBq/mmol]. Stability of the complex was checked in final formulation and in the presence of human serum for 48 h. The partition coefficient was calculated for the compound [log P=0.68]. The biodistribution of the labeled compound in vital organs of wild-type rats was studied using scarification studies and SPECT up to 24 h. A detailed comparative pharmacokinetic study for [111] In cation and [111]In-HMQ are performed up to 24h. The complex is mostly cleaned from the circulation by kidneys and is a compound rapidly washing from the circulation. The biodistribution of the complex in tumor models is on-going

Production, quality control and imaging of [64]Cu-ATSM in healthy rabbits for clinical applications

[[64]Cu]diacetyl-bis[N[4]-methylthiosemicarbazone] [[[64]Cu]ATSM] is a well-established hypoxia imaging tracer with reproducible production and significant specifity. In this work the high yield production and quality control as well as imaging studies in healthy rabbits is reported. Copper-64 produced via the [68]Zn[p, alpha n] [64]Cu nuclear reaction [30 MeV protons at 180 micro A] was used for the preparation of [[64]Cu]diacetyl-bis[N4-methylthiosemicarbazone][[ [64]Cu]ATSM]. Followed by quality control and administration to healthy rats as well as healthy rabbits for biodistribution and imaging studies respectively. [64]Cu[2+] [500 mCi, separation yield> 95%, radionuclide purity>96%] was used for [[64]Cu]ATSM production [radiochemical purity>99%, specific activity of 300 Ci/mmol] followed by administration to healthy rabbits and coincidence imaging demonstrating uptake in liver, kidney and bowel as shown by other reports in various rodents and human. [[64]Cu]ATSM radiopharmaceutical is produced and now available in large quantities for research and/or clinical trials in the country

Preliminary imaging studies of [[61]Cu] diacetyl-bis [N[4]-methylthiosemi-carbazone] in normal and hypoxic tumor models

[[61]Cu] diacetyl-bis [N[4] -methylthiosemicarbazone] [[[61]Cu] ATSM] is a well-established hypoxia imaging tracer with simple production and significant specifity. In this work the accumulation of the tracer is studied in wild-type, necrotic and hypoxic fibrosarcoma tumors. [[61] Cu] ATSM was prepared using ATSM ligand and [[61]Cu] CuOAc followed by i.v. administration and imaging studies in wid-type rats and hypoxic fibrosarcoma-bearing mic.e [[61] Cu] ATSM with high radiochemical purity [>99%, HPLC, RTLC] was injected to wild-type rats as well as hypoxic and necrotic fibrosarcoma-bearing mice followed by imaging up to 3 hours. [[61] Cu] ATSM was mainly accumulated in liver, as well as kidney and bladder and less but still significant in brain of wild-type rats. A significant and hypoxia-specific tumor/non tumor ratio in hypoxic models was observed by co-incidence imaging 2h post inection, while in necrotic and 12-week tumor-induced mice very slight tumor uptakes were detected. [[61]Cu] ATSM is a positron emission tomography [PET] radiotracer for selective tumor hypoxia imaging from necrotic and proliferative tumors