Abstract: Bone metastases are observed in a wide range of cancers leading to intolerable pain. While early detection can help the physicians in the decision of the type of treatment, various radiopharmaceuticals using phosphonates like 68Ga-EDTMP have been developed. In this work, due to the importance of absorbed dose, human absorbed dose of this new agent was calculated for the first time based on biodistribution data in Wild-type rats. 68Ga was obtained from 68Ge/68Ga generator with radionuclidic purity and radiochemical purity of higher than 99%. The radiolabeled complex was prepared in the optimized conditions. Radiochemical purity of the radiolabeled complex was checked by instant thin layer chromatography (ITLC) method using Whatman No. 2 paper and saline. The results indicated the radiochemical purity of higher than 99%. The radiolabelled complex was injected into the Wild-type rats and its biodistribution was studied up to 120 min. As expected, major accumulation was observed in the bone. Absorbed dose of each human organ was calculated based on biodistribution in the rats using RADAR method. Bone surface and bone marrow with 0.112 and 0.053 mSv/MBq, respectively, received the highest absorbed dose. According to these results, the radiolabeled complex is a suitable and safe option for PET bone imaging.
Abstract: The quality control procedures of a radiopharmaceutical include the assessment of its chemical purity. The method suggested by international pharmacopeias consists of a thin layer chromatographic run. In this paper, the method proposed by the United States Pharmacopeia (USP) is compared to a direct method to determine the final concentration of aminopolyether in Fludeoxyglucose (18F-FDG) preparations. The approach (no chromatographic run) was achieved by placing the thin-layer chromatography (TLC) plate directly on an iodine vapor chamber. Both methods were validated and they showed adequate results to determine the concentration of aminopolyether in 18F-FDG preparations. However, the direct method is more sensitive, faster and simpler when compared to the reference method (with chromatographic run), and it may be chosen for use in routine quality control of 18F-FDG.
Abstract: In this study, 177Lu-DOTATOC was prepared under optimized conditions (radiochemical purity: > 99%, radionuclidic purity: > 99%). The percentage of injected dose per gram (%ID/g) was calculated for organs up to 168 h post injection. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. The biodistribution data showed the significant excretion of the radioactivity from the kidneys. The adrenal and pancreas, as major expression sites for somatostatin receptor (SSTR), had significant uptake. A pharmacokinetic model of 177Lu-DOTATOC was presented by compartmental analysis which demonstrates the behavior of the complex.
Abstract: Despite the appropriate characteristics of 177Lu and DOTATOC, to our best knowledge, the therapeutic benefit of 177Lu-DOTATOC complex in breast cancer has not been reported until now. In this study, biodistribution of 177Lu-DOTA-TOC in mouse tumor model for evaluation of possible utilization of this complex in breast cancer treatment was investigated.177Lu was prepared with the specific activity of 2.6-3 GBq.mg-1 and radionuclidic purity higher than 99%. The radiolabeled complex was prepared in the optimized conditions with the radiochemical purity higher than 99%. The final solution was injected to the BALB/c mice with adenocarcinoma breast cancer. The biodistribution results showed major accumulation in the kidneys as the major excretion route and the somatostatin receptor-positive tissues such as pancreas compared with the other tissues. Also, significant uptake was observed in tumor even in longer time after injection. According to the results obtained in this research study, somatostatin receptors expressed in breast cancers can be targeted with DOTATOC analogues especially with 177Lu-DOTATOC as an ideal therapeutic agent.
Abstract: In the present study, highly effective iTLC single strip method for the determination of radiochemical purity (RCP) of 68Ga-BCA-peptides was developed (with no double-developing, changing of eluents or other additional manipulation). In this method iTLC-SG strips and commonly used eluent TFAaq. (3-5 % (v/v)) are used. The method allows determining each of the key radiochemical forms of 68Ga (colloidal, bound, ionic) separately with the peaks separation being no less than 4 σ. Rf = 0.0-0.1 for 68Ga-colloid; Rf = 0.5-0.6 for 68Ga-BCA-peptides; Rf = 0.9-1.0 for ionic 68Ga. The method is simple and fast: For developing length of 75 mm only 4-6 min is required (versus 18-20 min for pharmacopoeial method). The method has been tested on various compounds (including 68Ga-DOTA-TOC, 68Ga-DOTA-TATE, 68Ga-NODAGA-RGD2 etc.). The cross-validation work for every specific form of 68Ga showed good correlation between method developed and control (pharmacopoeial) methods. The method can become convenient and much more informative replacement for pharmacopoeial methods, including HPLC.
Abstract: An early diagnosis of bone metastasis is very
important for making a right decision on a subsequent therapy. One
of the most important steps to be taken initially, for developing a new
radiopharmaceutical is the measurement of organ radiation exposure
dose. In this study, the dosimetric studies of a novel agent for
SPECT-imaging of the bone metastasis, 111In-(4-
{[(bis(phosphonomethyl))carbamoyl]methyl}7,10bis(carboxymethyl)
-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (111In-BPAMD)
complex, have been carried out to estimate the dose in human organs
based on the data derived from mice. The radiolabeled complex was
prepared with high radiochemical purity in the optimal conditions.
Biodistribution studies of the complex was investigated in the male
Syrian mice at the selected times after injection (2, 4, 24 and 48 h).
The human absorbed dose estimation of the complex was made based
on data derived from the mice by the radiation absorbed dose
assessment resource (RADAR) method. 111In-BPAMD complex was prepared with high radiochemical
purity >95% (ITLC) and specific activities of 2.85 TBq/mmol. Total
body effective absorbed dose for 111In-BPAMD was 0.205
mSv/MBq. This value is comparable to the other 111In clinically used
complexes. The results show that the dose with respect to the critical
organs is satisfactory within the acceptable range for diagnostic
nuclear medicine procedures. Generally, 111In-BPAMD has
interesting characteristics and it can be considered as a viable agent
for SPECT-imaging of the bone metastasis in the near future.
Abstract: Abstract—[Tris (1,10-phenanthroline) lanthanum(III)]
trithiocyanate is a new compound that has shown high ability for
stopping the synthesis of DNA and also acting as a photosensitizer.
Nowadays, the radiation dose assessment resource (RADAR) method
is known as the most common method for absorbed dose calculation.
177Lu was produced by (n, gamma) reaction in a research reactor.
177Lu-PL3 was prepared in the optimized condition. The
radiochemical yield was checked by ITLC method. The
biodistribution of the complex was investigated by intravenously
injection to wild-type rats via their tail veins. In this study, the
absorbed dose of 177Lu-PL3 to human organs was estimated by
RADAR method. 177Lu was prepared with a specific activity of 2.6-3
GBq.mg-1 and radionuclide purity of 99.98 %. Final preparation of
the radiolabelled complex showed high radiochemical purity of >
99%. The results show that liver and spleen have received the highest
absorbed dose of 1.051 and 0.441 mSv/MBq, respectively. The
absorbed dose values for these two dose-limiting tissues suggest
more biological studies special in tumor-bearing animals.
Abstract: The measurement of organ radiation exposure dose is
one of the most important steps to be taken initially, for developing a
new radiopharmaceutical. In this study, the dosimetric studies of a
novel agent for SPECT-imaging of the bone metastasis, 111In-
1,4,7,10-tetraazacyclododecane-1,4,7,10 tetraethylene phosphonic
acid (111In-DOTMP) complex, have been carried out to estimate the
dose in human organs based on the data derived from rats. The
radiolabeled complex was prepared with high radiochemical purity in
the optimal conditions. Biodistribution studies of the complex was
investigated in the male Syrian rats at selected times after injection
(2, 4, 24 and 48 h). The human absorbed dose estimation of the
complex was made based on data derived from the rats by the
radiation absorbed dose assessment resource (RADAR) method.
111In-DOTMP complex was prepared with high radiochemical purity
of >99% (ITLC). Total body effective absorbed dose for 111In-
DOTMP was 0.061 mSv/MBq. This value is comparable to the other
111In clinically used complexes. The results show that the dose with
respect to the critical organs is satisfactory within the acceptable
range for diagnostic nuclear medicine procedures. Generally, 111In-
DOTMP has interesting characteristics and can be considered as a
viable agent for SPECT-imaging of the bone metastasis in the near
future.