Comparison of 99mTc and 123I for thyroid imaging.

Thyroid images were obtained with 99mTc and 123I, using a scintillation camera and pinhole collimator, from 85 patients selected from over 1,000 patients predisposed to the development of thyroid neoplasms by prior radiotherapy. In 66 of 85 patients 99mTc and 123I gave essentially similar information, whereas in 19 patients some thyroid-image disparity was seen. In 11 of these 19, focal areas of increased 99mTc concentration were not seen with 123I. Radioiodide images showed slightly better contrast than the 99mTc images but required a longer imaging time and usually did not provide more information; in a few cases 99mTc showed abnormalities more readily. Regardless of which radionuclide was used, oblique views were needed to define some abnormalities. Currently 123I does not provide significant advantages over 99mTc for routine thyroid imaging. However, 123I is preferred in patients with very poor thyroid function and in those with suspected retrosternal thyroid tissue. In addition, areas of increased 99mTc concentration should also be studied with 123I.     

Comparison of CVA imaging with 99mTc phosphates, 99mTc pertechnetate,and computed tomography

Summary A retrospective study was made of 111 patients who underwent computed tomography (CT) and nuclear brain scans, with both pertechnetate and phosphate bone agents (PHOS), within 7 days of each other. Specifically, 78 patients who had a recent cerebral vascular accident (CVA) were compared. There were no significant sensitivity differences between the methods. While these studies appear complementary, the most important criterion is the time after onset when the studies were performed. The axiom if the intensity of the phosphate scan exceeds that of the pertechnetate, the lesion must be a CVA is true, only if the study is performed within 4 weeks of onset. The most economical method for optimum detection of CVA, with avoidance of frequent errors, is an early CT followed by a PHOS brain scan about 14 days after ictus in those that have an initial negative CT.     

99mTc bone scanning agents--III. Preparation and gel chromatography of 99mTc(Sn)MDP complexes

The preparation of 99mTc(Sn)MDP was investigated as a function of pH, MDP concentration and Sn(II) concentration. The labeling efficiency was over 90% in the majority of the experiments and remained constant over the range pH 2-9. The MDP concentration had little effect, while the Sn(II) concentration had a significant positive influence. The complex formation appeared to be partly reversible. The formation of different complexes was investigated by means of gel chromatography under various experimental conditions. Altogether six complexes were found. At acid conditions two major complexes were found and at neutral pH one major complex. The presence or absence of a particular complex was mainly determined by the pH and by the MDP concentration. The Sn(II) concentration had very little effect. The results are compared with previous results of similar experiments with 99mTc(Sn)pyrophosphate.     

Technetium-99m (99mTc) mercaptoacetyltriglycine: update on the new 99mTc renal tubular function agent.

Technetium-99m (99mTc) mercaptoacetyltriglycine (MAG3) is a new renal radiopharmaceutical that was recently introduced as a 99mTc-labeled replacement for iodine-131 (131I) o-iodohippurate (OIH). Since its introduction, a wide variety of in vitro and in vivo studies have been performed to characterize the high-performance liquid chromatography (HPLC)-purified complex and kit formulations. [99mTc]MAG3 has a slower plasma clearance, a higher plasma protein binding, less red blood cell (RBC) penetration, a lower extraction ratio, and a smaller volume of distribution than OIH. Because of the slower plasma clearance, [99mTc] MAG3 cannot be used as a direct measurement of effective renal plasma flow. Simplified methods have been developed to calculate [99mTc]MAG3 clearances, as well as regression equations to convert these clearances to an equivalent OIH value. The image quality of [99mTc]MAG3 is superior to [131I]OIH; the renogram curves and the fraction of the dose of the two agents that appears in the urine are almost identical, even though the plasma clearance of [99mTc]MAG3 is only 50% to 65% that of OIH. [99mTc]MAG3 compares favorably with OIH in patients with a wide range of clinical problems. The radiation dose to a patient with normal renal function using standard imaging doses is higher for [99mTc]MAG3 than for [131I]OIH, but in patients with impaired renal function, the radiation dose from [131I]OIH is much higher than [99mTc]MAG3. [99mTc]MAG3 also provides superior image quality compared with [99mTc]diethylenetriaminepentaacetic acid (DTPA) in patients with impaired renal function, but it is important to note that [99mTc]MAG3 cannot be used to measure the glomerular filtration rate (GFR). [99mTc]MAG3 is the most promising 99mTc tubular function agent to date, and it has replaced OIH and [99mTc]DPTA in a number of institutions. However, there are physiologic differences between these three agents and, therefore, they should not be expected to behave identically in all clinical conditions.     

Labeling of ceftriaxone for infective inflammation imaging using 99mTc eluted from 99Mo/99mTc generator based on zirconium molybdate

Zirconium molybdate gel was prepared by mixing ⁹⁹Mo, produced from ⁹⁸Mo(n,γ) reaction and Zr solutions in nitrate media with excess H₂O₂, and used as the base material for ⁹⁹Mo/^99mTc generator. The prepared generator showed a good performance. ^99mTc eluted from the prepared generator passed the quality control tests with specifications meeting the requirements of European and US Pharmacopeias. The ^99mTc eluate was used for labeling of cephalosporin analogue, ceftriaxone, which was then assessed for infection imaging in a mouse model. ^99mTc-ceftriaxone was prepared at pH 9 with a radiochemical yield of 95±2% by adding ^99mTc to 30 mg ceftriaxone in the presence of 50 μg SnCl₂·2H₂O. Biodistribution studies in mice were carried out using experimentally induced infection in the left thigh using E. coli. Both thighs of the mice were dissected and counted to evaluate the ratio of bacterial infected thigh/contralateral thigh. ^99mTc-ceftriaxone showed high uptake in the infectious lesion (T/NT =5.6±0.6 at 4 h post injection). The abscess to normal muscle ratio indicated that ^99mTc-ceftriaxone could be used for infection imaging. Besides, in vitro studies showed that ^99mTc-ceftriaxone can differentiate between bacterial infection and sterile inflammation.     

99mTc bone scanning agents--II. Adsorption of 99mTc(Sn)pyrophosphate complexes on the mineral phase of bone

The adsorption of pyrophosphate, tin-pyrophosphate and 99mTc(Sn)pyrophosphate on Ca3(PO4)2 was investigated at pH 4.0 and pH 7.4. All components were radioactively labeled. Tin and reduced technetium were in most cases almost completely bound. The adsorption of pyrophosphate, tin(II) and technetium-99m at pH 4.0 was higher than at pH 7.4. The presence of tin gave rise to an increase of the pyrophosphate adsorption that was much larger than can be accounted for by a stoichiometric adsorption of tin-pyrophosphate. It is concluded that tin and technetium are bound as negatively charged complexes with pyrophosphate. Finally it is argued that the fraction of the bone scanning agent that reaches the bone surface is adsorbed completely by the mineral phase.     

99mTc]HYNIC-RGD for imaging integrin alphavbeta3 expression

There has been increasing interest in peptides containing the Arg-Gly-Asp (RGD) sequence for targeting of alpha(v)beta(3) integrins to image angiogenesis. [(18)F]Galacto-RGD has been successfully used for positron emission tomography applications in patients. Here we report on the preclinical characterization of a (99m)Tc-labeled derivative for single-photon emission computed tomography. c(RGDyK) was derivatized with HYNIC at the amino group of the lysine [c(RGDyK(HYNIC)) or HYNIC-RGD]. (99m)Tc labeling was performed using coligands (tricine and EDDA), as well as (99m)Tc(CO)(3)(H(2)O)(3). Radiolabeled peptides were characterized with regard to lipophilicity, protein binding and stability in buffer, serum and tissue homogenates. Integrin receptor activity was determined in internalization assays using alpha(v)beta(3)-receptor-positive M21 and alpha(v)beta(3)-receptor-negative M21L melanoma cells. Biodistribution was evaluated in normal and nude mice bearing M21, M21L and small cell lung tumors. HYNIC-RGD could be labeled at high specific activities using tricine, tricine-trisodium triphenylphosphine 3,3',3'-trisulfonate (TPPTS), tricine-nicotinic acid (NA) or EDDA as coligands. [(99m)Tc]EDDA/HYNIC-RGD, [(99m)Tc]tricine-TPPTS/HYNIC-RGD and [(99m)Tc]tricine-NA/HYNIC-RGD showed protein binding (<5%) considerably lower than [(99m)Tc](CO)(3)/HYNIC-RGD and [(99m)Tc]tricine/HYNIC-RGD. [(99m)Tc]EDDA/HYNIC-RGD revealed high in vitro stability accompanied by low lipophilicity with a log P value of -3.56, comparable to that of [(18)F]Galacto-RGD. In M21 cells for this compound, the highest level of specific and rapid cell uptake (1.25% mg protein(-1)) was determined. In vivo, rapid renal excretion, low blood retention, low liver and muscle uptakes and low intestinal excretion 4 h postinjection were observed. Tumor uptake values were 2.73% ID/g in M21 alpha(v)beta(3)-receptor-positive tumors versus 0.85% ID/g in receptor-negative tumors 1 h postinjection. Small cell lung tumors could be visualized using gamma camera imaging. [(99m)Tc]EDDA/HYNIC-RGD shows encouraging properties to target alpha(v)beta(3) receptors in vivo with high stability and favorable pharmacokinetics. Tumor uptake studies showed specific targeting of alpha(v)beta(3)-receptor-positive tumors with tumor-to-organ ratios comparable to those of [(18)F]Galacto-RGD.     

Biodistribution of lipophilic 99mTc complexes of Cyclam Derivatives

Several n-alkyl-cyclam derivatives were synthesized which form stable single component cationic chelates with ^99mTc These results suggest that the cyclam moiety in these derivatives complexes ^99mTc in the same manner as the underivatized macrocycle. Biodistribution studies in mice show that all of these chelates are cleared from circulation by both the kidneys and liver. The ratio and rates of clearance by these organ systems is related to lipid solubility. None of the lypophilic-cationic-^99mTc agents show any significant myocardial uptake. Also, these chelates show no significant ability to penetrate the blood-brain-barrier.     

A new radiopharmaceutical: 99mTc DMP for renal scanning

European Journal of Nuclear Medicine and Molecular Imaging - 99mTc-Dimercaptopropionic acid (DMP), a new renal scanning agent was synthesized, and the optimum preparative conditions and stability...     

99mTc(I) scorpionate complexes for brain imaging: synthesis, characterization and biological evaluation

The new dihydrobis(azolyl)borate ligand Na[H2B(tim(Me))(3,5-Me2pz)] (L1) was synthesized and used to prepare the complexes fac-[M(κ(3)-H(μ-H)B(tim(Me))(3,5-Me2-pz))(CO)3] (M = Re (4), 99mTc (4a)). L1 and 4 were characterized by common analytical techniques, including X-ray diffraction analysis for 4. The successful synthesis of complex 4a, obtained with high radiochemical purity, has shown for the first time that dihydrobis(azolyl)borate ligands combining 2- mercaptoimidazolyl and pyrazolyl rings are capable of stabilizing the fac-[99mTc(CO)3]+ unit. Complex 4a displays a high in vitro stability, in PBS (pH 7.4), indicating that the B-H...99mTc bond is retained even under physiological conditions. Biodistribution studies in mice have shown that 4a can cross the blood-brain barrier, emerging as a good alternative for the design of radiopharmaceuticals for brain imaging.     

Reversed-phase HPLC of [99mTc]tetraamine complexes

Radiochemical purity of a variety of cationic [^99mTc]tetraamine complexes can be conveniently determined by reversed-phase high performance liquid chromatography (HPLC) using styrene-divinylbenzene as the stationary phase. This reversed-phase HPLC system can also be used to rapidly measure the amount of unreduced [^99mTc]pertechnetate in preparations of hydrophylic anionic [^99mTc]chelates that are used in clinical nuclear medicine (e.g. [^99mTc]DTPA, and methylene diphosphonate).     

Standardization of 99mTc.

The radioactivity of 99mTc was standardized by the 4piPC-gamma coincidence method with two different modes. One is using coincidences between (119.5-142.6)keV conversion electrons and K X-rays, and the other is coincidences between the 2.13 keV conversion electrons and 140.5 keVgamma-rays. The background of the K X-ray peak and the sensitivity of the proportional counter (PC) to 140 keV gamma-rays were the main sources of uncertainties in the first case and low detection efficiency for conversion electrons in the second case. General coincidence equations were written, with specific forms, for the three measurement variants, including literature variant. Comparison with the ionization chamber calibration is reported.     

Asialoglycoprotein-receptor-targeted hepatocyte imaging using 99mTc galactosylated chitosan

This study investigated the usefulness of 99mTc hydrazinonicotinamide-galactosylated chitosan (HGC) in hepatocyte imaging. HGC was obtained by coupling the galactose moiety of both lactobionic acid and succinimidyl 6-hydrazinonicotinate hydrochloride (succinimidyl HYNIC). The coupled product was then radiolabeled with 99mTc using stannous chloride and tricine as reducing agent and coligand, respectively. Labeling efficiency was >90% both in room temperature and in serum up to 24 h after injection. The hepatic uptake properties of 99mTc HGC were studied in Balb/C mice. 99mTc HGC and 99mTc hydrazinonicotinamide chitosan (HC) were intravenously injected into mice, with receptor binding identified by coinjection with 9 and 14 mg of free galactose. Images were acquired with a gamma-camera. After injection via the tail vein of the mice, 99mTc HGC showed high selectivity for the liver, while 99mTc HC without a galactose group showed low liver uptake. In addition, the hepatic uptake of 99mTc HGC was blocked by coinjection of free galactose. Tissue distribution was determined at three different times (10, 60 and 120 min). The liver accumulated 13.16+/-2.72%, 16.11+/-5.70% and 16.55+/-2.28% of the injected dose per gram at 10, 60 and 120 min after injection, respectively. 99mTc HGC showed specific and rapid targeting of hepatocytes. It is a promising receptor-specific radiopharmaceutical with potential applications in liver imaging for the evaluation of hepatocytic function.