Rapid and accurate assessment of the activity measurements in Brazilian hospitals and clinics.

Traceability in Nuclear Medicine Service (NMS) measurements was checked by the Institute of Radioprotection and Dosimetry (IRD) through the Institute of Energy and Nuclear Research (IPEN). In 2016, IRD ran an intercomparison program and invited Brazilian NMS authorized to administer 131I to patients. Sources of 131I were distributed to 33 NMSs. Three other sources from the same solution were sent to IRD, after measurement at IPEN. These sources were calibrated in the IRD reference system. A correction factor of 1.013 was obtained. Ninety percent of the NMS comparisons results are within ±10% of the National Laboratory of Metrology of Ionizing Radiation (LNMRI) value, the Brazilian legal requirement.

Comparison of the effect of knee synovectomy in haemophilic patients with 153Sm- and 90Y-labelled hydroxyapatite 1 year after.

To compare the use of 740 Mbq (20 mCi) of (153) Sm and 185 Mbq (5mCi) of (90) Y, both labelling hydroxyapatite (HA), for knee synovectomy in haemophilic patients, 1 year after the intervention. Thirty three men (36 knees) were studied, divided into two groups: 1 - treatment using 740 Mbq of (153) Sm-HA: 20 knees of 18 patients, with mean age of 21.4 ± 13.3 years (ranging from 7 to 56 years) and mean Pettersson score of 5.3; 2 - treatment using 185 Mbq of (90) Y-HA: 16 knees of 15 patients, with mean age of 26.3 ± 10.3 (ranging from 7 to 51 years) and mean Pettersson score of 6.3. The following criteria were adopted for the evaluation before and 1 year after synovectomy: reduction in haemarthrosis episodes and pain using a visual analogue scale, as well as improved joint mobility. The occurrence of adverse events in the treatment was also considered. The chi-square, Wilcoxon and Mann-Whitney tests were used with P ≤ 0.05 set as significant. The occurrence of haemarthrosis declined by 65.7% with the use of (153) Sm-HA and 82.6% for (90) Y-HA, with no statistical difference between the groups (P = 0.632); pain reduction was 42.5% in group 1 and 30.7% in group 2, once again with no statistical difference (P = 0.637). Improvement in joint mobility was not significant for both groups. Two cases of mild reactive synovitis were observed in group 1 and one in group 2, which cleared up without medical intervention. Although the beta energy from (90) Y is the gold standard for knee synovectomy, higher activities of (153) Sm may be used in places which have only production of this material.

Preparation of [In-111]-labeled-DTPA-bombesin conjugates at high specific activity and stability: evaluation of labeling parameters and potential stabilizers.

The aim of the present work was to obtain stabilized high specific activity (HSA) (111)In-labeled bombesin conjugates for preclinical evaluations. Parameters influencing the kinetics of labeling were investigated and the effect of stabilizers on HSA radiopeptides stability at room temperature were systematically categorized applying chromatography techniques. A SA of 174 GBq/µmol was achieved with high radiochemical purity, but the labeled compounds exhibited low stability. The addition of stabilizers avoided their radiolysis and significantly increased their stability.

Novel series of (177)Lu-labeled bombesin derivatives with amino acidic spacers for selective targeting of human PC-3 prostate tumor cells.

AIM: Bombesin (BBN) has demonstrated the ability to bind with high affinity and specificity to GRP receptor, overexpressed on human prostate cancer. A large number of BBN derivatives have been synthesized for this purpose but most of them exhibit high abdominal accumulation, which may represent a problem in their clinical use due to serious side effects to patients. In this study we describe the results of radiolabeling with lutetium-177, stability and in vivo studies of novel phenyl-glycine-extended bombesin derivatives. The spacers were inserted to improve bombesin in vivo properties and to reduce its target to non-tumor sites. METHODS: Preliminary studies were done to establish the ideal conditions for labeling bombesin derivatives. Chromatography systems were applied to determine free lutetium and the stability of the preparations was evaluated either after storing at 2-8 ºC or incubation in human serum at 37 ºC. In vivo experiments included biodistribution, pharmacokinetics and SPECT images and were performed in Balb-c and Nude mice bearing PC-3 xenografts. RESULTS: The derivatives were labeled with high yield and kept stable at 2-8 ºC and are metabolized by human serum enzymes. In vivo studies showed fast blood clearance of labeled peptides and rapid excretion, performed mainly by renal pathway. In addition, biodistribution and imaging studies showed low abdominal accumulation and significant and specific tumor uptake of (177)Lu-labeled derivatives. CONCLUSIONS: The derivative with longer spacer holds a higher potential as radiopharmaceutical for prostate tumor diagnosis and the derivatives with shorter spacers are potential radiopharmaceuticals for prostate tumor treatment.

In vivo comparative study of hydroxyapatite labeled with different radioisotopes: evaluation of the scintigraphic images.

Radyosinovectomy (RSV) is a radiotherapeutic modality where a beta-emitting radionuclide is administered locally by intra-articular injection on the form of a colloid or radiolabeled particulate. RSV is a well-accepted therapeutic procedure in inflammatory joint diseases and has been successfully employed for more than 50 years as a viable alternative to surgical and chemical synovectomy. The aim of this work is to compare the in vivo stability of hydroxyapatite labelled with (177)Lu, (90)Y and (153)Sm. All radionuclides were labelled with high yield and were retained in the joint for 7 days, showing stability and usefulness as tools in the RSV treatment. A similar retention of the products in the muscle was observed when the particles were administrated in the muscle. However, the pure form of the radionuclides were rapidly cleared from the blood and accumulated in the liver when injected i.v.. Although (153)Sm-HA is already available for nuclear medicine procedures and clinical studies with (90)Y-HA have been developed, (177)Lu-labeled RSV agents will be economically more viable and has not been studied yet. Its favorable characteristics contribute to follow, to predict and asses the success of RSV by bone scintigraphy studies.

Radiolabeling of substance P with lutetium-177 and biodistribution study in rat pancreatic tumor xenografted nude mice.

Pancreatic tumor (PT) is a neuroendocrine neoplasm that usually origin metastases in the respiratory and gastrointestinal tract. The presence of peptide receptors at the cell membrane of PT constitutes the basis of the clinical use of specific radiolabeled ligands for its diagnosis and targeted therapy. Substance P (SP), an 11-amino acid peptide which has an important role in modulating pain transmission trough neurokinin type 1 (NK1r) and 2 receptors (NK2r), may play a role in the pathogenesis of PT, because approximately 10% of these tumors overexpress NK1r. The aim of the present work was to produce a pure and stable SP analog (DOTA-SP) radiolabeled with lutetium-177 ((177)Lu), and to evaluate its in vivo target to AR42J pancreatic tumor cells in Nude mice, in other to verify if SP can be used in this pancreatic tumor detection and treatment. Substance P was successfully labeled with high yield (>99%) at optimized conditions and kept stable for more than 72 hours at 2-8 degrees C and 4 hours in human plasma. Biodistribution studies showed that SP excretion was mainly performed by renal pathway. In addition, (177)Lu-DOTA-SP showed higher uptake by tumor than normal pancreas, indicating the presence of NK receptors in AR42J pancreatic tumor.

Development of a new bombesin analog radiolabeled with lutetium-177: in vivo evaluation of the biological properties in Balb-C mice.

In this work we describe the first results of radiolabeling with lutetium-177 ((177)Lu) and in vivo biodistribution and pharmacokinetics studies in normal Balb-c mice of a new bombesin analog (BEFG2)--DOTA-Phe-X-BBN(6-14), where X is a spacer of two aminoacids. Bombesin (BBN) is an amphibian analog of human gastrin releasing peptide (GRP). Development of radiolabeled BBN derivatives as agents for diagnostic imaging and systemic radiotherapy has increased considerable because of the observation that GRP receptors (GRPr) are over-expressed in a variety of human tumor cells, such as prostate tumor cells. (177)Lu-labeled peptides are attractive due to the excellent radiophysical properties and commercial availability of the radiometal. BEFG2 was successfully labeled with high yield and kept stable for more than 96 hours at 2-8 degrees C and 1 hour in human plasma. Data analysis obtained from the in vivo studies showed that the amount of BEFG2 present in plasma decreased rapidly and became almost undetectable at 60 min p.i., indicating rapid peptide excretion, which is performed mainly by renal pathway. In addition, biodistribution and single photon emission tomography showed low abdominal accumulation of (177)Lu-DOTA- Phe-X-BBN(6-14), indicating that this analog is a potential candidate for tumors target therapy.

Tecnetium-99m as alternative to produce somatostatin-labeled derivatives: comparative biodistribution evaluation with 111In-DTPA-octreotide.

Synthetic somatostatin (SST) analogues have been used in the preparation of receptor-specific radiopharmaceuticals for diagnostic and therapy of neuroendocrine tumors. This work studied the labeling conditions with (99m)Tc and biological distribution in Swiss mice of two SST analogs (HYNIC-Tyr(3)-Octreotide and HYNIC-Tyr(3)-Octreotate) and compared the biodistribution pattern with (111)In-DTPA-Octreotide. Biological distribution studies were performed after injection of radiopharmaceuticals on Swiss mice. Labeling procedures resulted on high radiochemical yield for all three preparations and the labeled products presented high in vitro stability. Biological distribution studies evidenced similar general biodistribution of (99m)Tc-labeled peptides when compared with indium-labeled peptide with fast blood clearance and elimination by urinary tract. Kidneys uptake of (99m)Tc-HYNIC-TATE are similar to (111)In-DTPA-Octreotide, and both are significantly higher than (99m)Tc-HYNIC-OCT. All labeled peptides presented similar uptake on liver, but the retention in time at intestines, particularly at large intestine, was more expressive for (111)In-labeled peptide. The %ID of (99m)Tc-HYNIC-OCT and (99m)Tc-HYNIC-TATE in organs with high density of SST receptors like pancreas and adrenals were significant and similar to obtained for (111)In-DTPA-Octreotide, confirming the affinity of these radiopharmaceuticals for the receptors.

A comparative study of 131I and 177Lu labeled somatostatin analogues for therapy of neuroendocrine tumours.

This work analysed the influence of the chelating group and radioligand on somatostatin analogues in vivo and in vitro properties. The presence of DOTA in the radioiodinated peptide produced a labeled analogue with similar blood kinetics and biodistribution to (177)Lu-DOTATATE and with lower abdominal uptake than (131)I-TATE. In addition, (131)I-DOTATATE showed significative tumour uptake, despite not so persistent after 24h. (131)I-DOTATATE can represent a cost-effective alternative to lutetium labeled peptide for neuroendocrine tumours therapy.