99mTc-amoxicillin: A novel radiopharmaceutical for infection imaging

Amoxicillin, a penicillin derivative was synthesized as ready-to-used single vial kit and radiolabeled with technetium-99m. Various trials have been carried out to optimize the concentration of stannous chloride, amoxicillin, pH and reaction time. Radiochemical purity, in vitro and in vivo stability, partition co-efficient, protein binding and biodistribution in rabbit infected with Streptococcus pneumoniae were studied. The biodistribution studies in rabbit showed that ^99mTc-amoxicillin started to accumulate in the infected area at 1-h postadministration. ^99mTc-amoxicillin may prove itself as potential novel radiopharmaceutical for imaging infections caused by many bacteria.     

A99mTc-Sn-pyrophosphate complex: A stable,lyophilized radiopharmaceutical for skeletal scanning

“Kit” composition was determined on the basis of biodynamic data obtained when the Sn/pyrophosphate ratio, pH and other parameters were varied. In vivo distribution of different^99mTc-Sn-pyrophosphate complexes permitted the selection of the most suitable complex for skeletal scanning.     

Tracers for radiopharmaceutical production facilities

Fecal radiobioassay is an essential and sensitive tool to estimate the internal intake of actinides after a radiological incident. A new fecal analysis method, based on lithium metaborate fusion of fecal ash for complete sample dissolution followed by sequential column chromatography separation of actinides, has been developed for the determination of low-level Am and Cm in a large size sample. Spiked synthetic fecal samples were analyzed to evaluate method performance against the acceptance criteria for radiobioassay as defined by ANSI N13.30; both satisfactory accuracy and repeatability were achieved. This method is a promising candidate for reliable dose assessment of low level actinide exposure to meet the regulatory requirements of routine radiobioassay for nuclear workers and the public.     

188Rhenium-EDTMP: A potential therapeutic bone agent

Bone seeking radiopharmaceuticals such as ethylenediaminetetramethylene phosphonate (EDTMP) complexes of ¹⁵³Sm and ¹⁶⁶Ho are receiving considerable attention for therapeutic treatment of bone metastases. Rhenium-188 has both beta-particle emissions for a therapeutic effect and gamma-emissions for imaging and it is available from an in-house generator system similar to the current ^99mTc generator, which makes it convenient for clinical use. The preparation of ¹⁸⁸Re-EDTMP is described using ¹⁸⁸Re, which was obtained from the alumina-based ¹⁸⁸W/¹⁸⁸Re generator. Dependence of the radiolabeling yield of ¹⁸⁸Re-EDTMP on reducing agent concentration, EDTMP concentration, incubation time, pH and addition of carrier was examined. In the case of optimum conditions, the radiolabeling yields of ¹⁸⁸Re-EDTMP were ~98% for carrier-free as well as carrier-added ¹⁸⁸Re. The addition of ascorbic acid plays an important role in the stability of carrier-free as well as carrier-added ¹⁸⁸Re-EDTMP preparations. The biodistribution of carrier-free and carrier-added ¹⁸⁸Re-EDTMP compounds in rats was also studied. The results show that ¹⁸⁸Re (carrier-added)-EDTMP is a potential bone pain palliation radiopharmaceutical due to its high skeletal uptake, rapid blood clearance and relatively low soft tissue absorption.     

A normoxic acrylic acid polymer gel for dosimetery in radiation therapy

Journal of Radioanalytical and Nuclear Chemistry - A novel low toxic normoxic polymer gel dosimeter containing acrylic acid monomer is prepared and characterized for dosimetry in radiotherapy. Gel...     

99mTc-AMD3100: A novel potential receptor-targeting radiopharmaceutical for tumor imaging

<正>The chemokine CXCR4 receptor is over-expressed in a wide variety of tumors.In this study,AMD3100,which was a prototype non-peptide antagonist of CXCR4 receptor,was labeled with ~(99m)Tc.~(99m)Tc-AMD3100 was verified by thin layer radio chromatography(TLRC).The tumor-localizing properties of ~(99m)Tc-AMD3100 were evaluated and proved in mice bearing Hep-G2 tumor xenograft.~(99m)Tc-AMD3100 was a promising,novel receptor-specific radiopharmaceutical with potential application in the imaging of human tumors.     

Cu-ATSM: a radiopharmaceutical for the PET imaging of hypoxia

Copper(II)-diacetyl-bis(N(4)-methylthiosemicarbazone), Cu-ATSM, labeled with a positron emitting isotope of copper ((60)Cu, (61)Cu, (62)Cu or (64)Cu) has been shown, in vitro and in vivo, to be selective for hypoxic tissue. In silico studies have explored the mechanism of its hypoxia selectivity, and clinical studies with this agent have shown non-invasive imaging data that is predictive of a cancer patients' response to conventional therapy. This Perspective discusses the evolution of Cu-ATSM, how its selectivity can be improved upon, and where this metal-ligand platform could be taken in the future.     

[161Tb]Tb-Thz-Phe-D-Trp-Lys-Thr-DOTA: A potential radiopharmaceutical for the treatment of neuroendocrine tumors

Thz-Phe-D-Trp-Lys-Thr-DOTA, a conjugate of the DOTA chelator and the Thz-Phe-D-Trp-Lys-Thr pentapeptide, was labeled with ¹⁵²Eu and ¹⁶¹Tb radionuclides, where ¹⁶¹Tb has decay characteristics suitable for its use in cancer therapy. For the [¹⁵²Eu]Eu-Thz-Phe-D-Trp-Lys-Thr-DOTA complex, the biodistribution in nude mice bearing IMR-32 tumors was evaluated for the first time. It was shown that the complexes of the conjugate demonstrate accumulation in the tumor at the level of DOTA-TATE, another peptide conjugate widely used in nuclear medicine for the diagnosis and therapy of neuroendocrine tumors, which allows Thz-Phe-D-Trp-Lys-Thr-DOTA to be considered as a potential biological vector for radiopharmaceuticals.     

Single vial formulation for theranostic radiopharmaceutical preparation

The present work was aimed at development of pharmaceutical grade single vial kit like formulation of somatostatin analogue, DOTA–Tyr³–Thr⁸-Octreotide (DOTATATE) suitable for radiolabeling with both diagnostic (⁶⁸Ga) and therapeutic (¹⁷⁷Lu) radioisotope. Single vial kit like formulation of DOTATATE was prepared. Radiolabeling methods with ⁶⁸Ga and ¹⁷⁷Lu were standardized. The pharmaceutical purity and stability of formulation was studied over a period of 6 months. Pharmacokinetics of radiolabeled preparations was studied in Swiss mice. DOTATATE formulation with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer was successfully prepared. Both ⁶⁸Ga–DOTATATE and ¹⁷⁷Lu–DOTATATE complexes were formed with >95 % radiochemical purity. Biodistribution studies of ⁶⁸Ga–DOTATATE and ¹⁷⁷Lu–DOTATATE complexes in Swiss mice revealed fast clearance of activity via renal route. Single vial kit like formulation suitable for easy preparation of ⁶⁸Ga–DOTATATE and ¹⁷⁷Lu–DOTATATE at hospital radiopharmacy was successfully demonstrated.     

Single vial kit formulation for preparation of PET radiopharmaceutical: 68Ga-DOTA-TOC

This paper describes the development of a lyophilized cold kit of DOTA-[Tyr³]-Octreotide (DOTA-TOC) for instant compounding of ⁶⁸Ga-DOTA-TOC, suitable for diagnosis of neuroendocrine tumors. The work involved formulation of DOTA-TOC kits, optimization of radiolabeling, quality control of ⁶⁸Ga-DOTA-TOC and animal biodistribution studies. The prepared kits enable a reliable method for preparation of ⁶⁸Ga-DOTA-TOC of high radiochemical purity and excellent stability. Availability of such kits along with ⁶⁸Ge/⁶⁸Ga generators is expected to stimulate the widespread use of ⁶⁸Ga-DOTA-TOC in nuclear medicine practice in developing countries.     

186Re/188Re labeled polypeptide microspheres as a potential radiation synovectomy agent

Polypeptide microspheres containing polycysteine crosslinked with polylysine were prepared and radiolabeled with¹⁸⁶Re and¹⁸⁸Re. High labeling yields with the microspheres with both¹⁸⁶Re and¹⁸⁸Re (97%) were obtained, and above 99% retention of radiolabels in water in 24 hours was obtained. Rhenum-186 labeled polycysteine and polylysine microspheres (11 ratio, 20 m as mean diameter) were injected intra-articularly into the rear stifes (knee joints) of normal New Zealand white rabbits. About 87% of injected dose was retained in rabbit stifles and adjacent tissues in 96 hours after injection, while most of the activity lost from the joints was excreted in the urine. Due to its simplicity of preparation and radiolabeling, versatility, and biodegradability, this type of conjugate system may become the therapeutics of choice for radiation synovectomy.     

The tungsten-188/rhenium-188 generator: Effective coordination of tungsten-188 production between the HFIR and BR2 reactors

The rapidly increasing therapeutic applications of ¹⁸⁸Re in nuclear medicine, oncology and interventional cardiology require routine production of large, multi-Curie levels of the ¹⁸⁸W parent. The capability and effective coordination of back-up production sites is important to insure that high level ¹⁸⁸W/¹⁸⁸Re generators are continually available. We have coordinated ¹⁸⁸W production at the High Flux Isotope Reactor (HFIR - Oak Ridge, US) with production at the BR2 Reactor (Mol, Belgium) characterized by peak thermal neutron fluxes of 2.51·0¹⁵ (HFIR) and 1·10¹⁵ (BR2) neutrons/cm²·sec, respectively. The long 69-day physical half-life permits receipt of ¹⁸⁸W from BR2 within 0.25 T _1/2's, even after the 12-day post irradiation cooling required for ¹⁸⁷W decay (T _1/2 = 24 hours). Since ¹⁸⁸W production by double neutron capture of enriched ¹⁸⁶W is a function of the square of the thermal neutron flux, HFIR production (4-5 Ci ¹⁸⁸W/g ¹⁸⁶W/cycle) is higher than at the BR2 (1.0-1.1 Ci/g ¹⁸⁶W/cycle). However, the specific activity (SA) of BR2-produced ¹⁸⁸W is still about 0.8-0.9 Ci/g after processing at ORNL following shipment from Belgium. This SA is sufficiently high to permit fabrication of 1 Ci generators suitable for clinical use, since simple post elution concentration of the saline bolus (30-50 ml) obtained from the generator can provide samples with high specific volume (1 ml volume). The time periods from reactor push in Mol and completion of processing, fabrication and shipment of generators from Oak Ridge have been 19-21 days. Six campaigns have been successfully completed since 1998, with processed levels of ¹⁸⁸W in Oak Ridge from 8-26 Curies/campaign. ¹⁸⁸W has been provided to MAP Medical technologies Oy (Tikkakoski, Finland) for fabrication and distribution of generators for use at IAEA-supported research projects in developing countries. We have thus established and demonstrated an effective collaboration between the Studiecentrum voor Kernenergie-Centre d'Etude de l'Energie Nucléaire (SCK·CEN) and ORNL for back-up production of ¹⁸⁸W. This collaboration continues to be especially helpful during periods when interruption of HFIR operation is necessary for maintenance and upgrades.     

Reduction of radiation dose to the worker in preparing the radiopharmaceutical solution by a simple shielding equipment

In order to reduce radiation dose to the hands of examiners who prepare and aspirate radiopharmaceuticals, we made a prototype of simplified manually-operated dispense system, which the syringe and the vial shield with lead were set in the small box made of lead and lead glass. The result showed that our dispense system allowed substantial reduction of radiation dose to the hands and rapid preparation of radiopharmaceuticals compared with the conventional lead shield syringe system, and allowed closer operation, smaller dead volume and lower cost compared with the conventional automatic system.     

An efficient one-pot method for the large-quantitative production of radiopharmaceutical ligand: diazadioximes

An efficient one-pot procedure for the preparation of diazadioxime was described. Treatment of ketooximes with alkyldiamine followed by NaBH4 in dry ethanol afforded the corresponding d,l-diazadioximes in 56--74% yield without isolation of the intermediates.     

Peptide labeling using 188Re, 188Re-MAG3 and 153Sm-H1ETA: A comparison on their in vitro lipophilicity

Lanreotide peptide was labeled with ¹⁵³Sm-H₁ETA and ¹⁸⁸Re-MAG₃ in order to evaluate whether or not their conjugation to the peptide produce significant differences of the in vitro lipophilicity with respect to the ¹⁸⁸Re-lanreotide prepared by the direct labeling method (highly lipophilic). The differences of lipophilicity between the complexes, were evaluated using a reverse phase HPLC system. The measured lipophilicity of ¹⁵³Sm-H₁ETA-lanreotide, ¹⁸⁸Re-MAG₃-lanreotide and ¹⁸⁸Re-lanreotide was taken to be the capacity factor [k" = (t _R-t ₀)/t ₀ where t _R is the retention time and t ₀ is the dead time] for each of the complexes under identical chromatography conditions. Results showed that the in vitro lipophilicity decreased in the order ¹⁸⁸Re-lanreotide (direct labeling), ¹⁸⁸Re-MAG₃-lanreotide and ¹⁵³Sm-H₁ETA-lanreotide. Since the last one has a capacity factor (k") similar to that of ¹⁸⁸Re-MAG₃, some renal elimination for ¹⁵³Sm-H₁ETA-lanreotide could be expected, which probably would reduce the unnecessary radiation dose to normal tissues.     

<Superscript>99m</Superscript>Tc-exorphin C: A new peptide radiopharmaceutical for tumor imaging

Summary The aim of this study was to label exorphin C with ^99mTc and to examine its usefulness as opioid receptor binding radiopharmaceutical in Albino Wistar rats. Exorphin C, which is a peptide with 5 aminoacids, was labeled with ^99mTc using glucoheptonate (GH) as a bifunctional chelating agent. Labeling efficiency was higher than 98%. The compound was stable for at least 5 hours at room temperature. Mammary tumor bearing Albino Wistar rats were imaged using gamma-camera. Biodistribution studies were also performed. Results demonstrated that ^99mTc-glucoheptonate-exorphin C (^99mTc-GE) analogs may be useful as a new class of receptor-binding peptides for the diagnosis and therapy of some cancer diseases related with opioid receptor-expressing tissues.     

Copper(II) cyclam-based complexes for radiopharmaceutical applications: synthesis and structural analysis

Two molecular structures of the copper(II) complex, Cu(H(2)TETA), have been determined by X-ray crystallography. The Jahn-Teller distortion differs between the two structures; occurring either along the axis of the pendant acetate arms or across the macrocyclic ring. An analysis of deposited data from over one hundred copper(II) cyclam X-ray structures in the Cambridge Structural Database (CSD) reveals that Jahn-Teller distortion across the ring is highly unusual for such compounds in the solid state. Novel chelators based on the piperazino/side-bridged cyclam have been prepared and copper(II) complexes formed. The single crystal X-ray structures of two copper(II) complexes, with either an ester or acid N-pendant arm, have been determined and in both cases the pendant arm is bound to the metal centre.     

Preparation of 188Re-labeled hydroxyapatite for radiosynovectomy

Hydroxyapatite (HA), a natural constituent of bone, was synthesized. HA particles were radiolabeled with ¹⁸⁸Re. Radiolabeling efficiency was 95%. In vitro studies showed 5% loss of activity from particles in normal saline over a period of 2 days, whereas a dissociation rate of 9% was observed in human serum albumin.