A CD(4)/T(4) receptor peptide ligand labeled with technetium-99m: synthesis and biological activity

The octapeptide D-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-NH₂ ([D-Ala¹]TNH₂), an analog of peptide T (H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH) associated with CD₄/T₄ receptors involved in human immunodeficiency virus infection, was combined with the chelating polyazamacrocycle 1,4,8,11-tetraazacyclotetradecane (cyclam) to afford the bifunctional ligand cyc-[D-Ala¹]TNH₂. This was then reacted with [^99mTcO₄]⁻ and Sn²⁺ to yield the monocationic complex [^99mTc(O)₂(cyc-[D-Ala¹]TNH₂)]⁺. Biological activity of both the cyclam-peptide conjugate and the resulting Tc-99m complex were evaluated by measuring their chemotactic indexes. Results showed that N-cyclam acylation and subsequent labeling with Tc-99m of [D-Ala¹]TNH₂ were tolerated, and both cyc-[D-Ala¹]TNH₂ and [^99mTc(O)₂(cyc-[D-Ala¹]TNH₂)]⁺ retained the high chemotactic capacity of the original octapeptide. Biodistribution of the Tc-99m complex was carried out in rats. Fast blood clearance and no accumulation in organs of interest were observed.     

Synthesis and biodistribution of Tc-carbonyltechnetium-labeled fatty acids

In order to image myocardial metabolism, ^99mTc(CO)₃⁺ complexes containing fatty acids were evaluated. At first, 11-(1-imidazolyl)-undecanoic acid (IUA) and 11-(2-(4-bromo-phenylazo)-1-imidazolyl)-undecanoic acid (BPIUA) were synthesized and the corresponding carbonyltechnetium-labeled complexes were prepared. However, unfortunately similar to those of other technetium-labeled fatty acid analogs, the biodistribution studies of ^99mTc(CO)₃–IUA and ^99mTc(CO)₃–BPIUA in mice demonstrated poor heart-to-blood ratios, thus these complexes cannot be used as heart-imaging reagents. In addition, Tween-80 can improve the biodistribution of the complexes for myocardial imaging.     

Tc-2GAM: A tracer for renal imaging

We propose a renal imaging agent, the ^99mTc complex of the bidentate-N,S chelate N-(mercaptoacetyl) glycine (^99mTc-2GAM), with the imaging characteristics of ^99mTc-DMSA but a faster kidney uptake; chemical evidence supports the formulation of ^99mTc-2GAM as [Tc^V(O)(GAM)₂]⁻. After biodistribution and toxicity studies in animals, ^99mTc-2GAM was evaluated in five normal volunteers. ^99mTc-2GAM is rapidly cleared from the blood ( ) and 50% of the ID is excreted in the urine in the first 2 h. Dynamic data show a rapid renal uptake that increases up to 1 h with no significant wash-out between 1 and 8 h. The uptake in each kidney ranges from 11.3% to 20.7% ID. Low, stable liver uptake is observed. No significant activity is detected in other organs. We showed no differences between ^99mTc-2GAM and ^99mTc-DMSA compared in three patients with unilateral kidney disease. We conclude that ^99mTc-2GAM has good practical and dosimetric features for renal imaging.     

Molecular recognition and stability of Tc-UBI 29–41 based on experimental and semiempirical results

^99mTc-UBI 29–41 is an antimicrobial peptide fragment that directly radiolabeled with ^99mTc shows high in vitro and in vivo stability, rapid background clearance, minimal accumulation in non-target tissues and rapid detection of infection sites. Molecular mechanics (MM) calculation has been an essential tool in explaining experimental results associated with molecular recognition and stability. This work is an attempt to explain the ^99mTc-UBI 29–41 specificity for bacteria and to understand from a structural point of view, the experimental results indicative of a molecular recognition and stability not well favored for two other cationic peptides (^99mTc-Tat-1-Scr and ^99mTc-Tat-2-Scr ) used as control. Structures of ^99mTc-UBI, ^99mTc-Tat-1-Scr, ^99mTc-Tat-2-Scr and of the corresponding free cationic peptides were built and the optimized structures, in the best stable configurations, were calculated by a MM procedure. In order to correlate the calculated and experimental results, in vitro stability tests with cysteine challenge and stability to dilution in human serum and in saline solution, were performed for the three labeled cationic peptides. The three complexes can be represented by the general formula [Tc(V)(O)(H₂O)₂(Lys_n=1,2-Arg_n=0,1-peptide)]^10+,11+. The potential energies were 104.5, 95.6 and 90.8 kcal/mol for ^99mTc-Tat-1-Scr, ^99mTc-Tat-2-Scr and ^99mTc-UBI 29–41, respectively. Experimental and calculated results were in good agreement. It is thus possible to predict and explain that in similar solution media ^99mTc-Tat-2-Scr would be more stable than ^99mTc-Tat-1-Scr and why ^99mTc-UBI shows the highest stability. In conclusion, the in vitro specific binding to bacteria and the accumulation at infection sites in humans of ^99mTc-labeled UBI could be the result of its high thermodynamic stability, selectivity and stereospecificity.     

Evaluation of Tc-labeled modified serum albumin for tumor detection

Serum albumin (SA) modified and labeled with ¹³¹l-tyramine N-1′-desoxysorbitol (¹³¹I-TDS) has been shown to localize in tumors [Sinn et al., (1990) Nucl. Med. Biol. Part B 17, 819–827]. We prepared similar TDS complexes labeled with ^99mTc and evaluated their potential for tumor imaging. Derivatization of SA with TDS was optimized using cyanuric chloride or 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDAC) as coupling agents. A high TDS loading yield of 38 mol/mol SA was obtained with the latter reagent. Modified SA (8 and 38 mol TDS/mol SA) were labeled with ^99mTc via the stannous reduction method and injected i.v. into EMT-6 tumor bearing mice. ¹²⁵I-TDS-SA (8 mol ¹²⁵I-TDS/mol SA) revealed a high tumor uptake of 10% ID/g at 3 h post-injection. The ^99mTc-labeled SA and TDS-SA complexes lacked tumor specificity, instead TDS loading of SA resulted in increased liver/spleen uptake, suggesting colloid formation. This study confirms the potential of modified SA for tumor imaging but highlights the importance of choice of radioisotope, as well as site of attachment of the radiolabel to the modified SA for optimal tumor localization.     

Rhenium-188 and technetium-99m nitridobis(N-ethoxy-N-ethyldithiocarbamate) leucocyte labelling radiopharmaceuticals: [ReN(NOET)2] and [TcN(NOET)2], NOET = Et(EtO)NCS2: Their in vitro localization and chemical behaviour

In this study, we have investigated the preparation of rhenium-188 nitridobis(N-ethoxy-N-ethyldithiocarbamate) [¹⁸⁸ReN(NOET)₂] (NOET = Et(EtO)NCS₂), analogous to the known technetium-99m radiopharmaceutical. The new ¹⁸⁸Re complex was synthesized in good yield with a satisfactory radiochemical purity, using a kit method. The subcellular localization of both radiopharmaceuticals in granulocytes was observed by microautoradiography. The uptake was independent of the radionuclide and predominantly nuclear. Furthermore, HPLC was used to characterize the ^99mTc complex before and after blood cell labelling and revealed that the intact radiopharmaceutical was involved.     

Synthesis and biodistribution of a new Tc nitrido complex as a potential myocardial and cerebral imaging agent

The bis(N-methyl, N-cyclohexyl dithiocarbamato) nitrido technetium-99m complex [^99mTcN(MECHDTC)₂] (MECHDTC: N-methyl, N-cyclohexyl dithiocarbamato) has been synthesized through a ligand-exchange reaction. The two-step procedure consisted of an initial reaction of ^99mTcO₄⁻ with succinic dihydrazide in the presence of stannous chloride as reducing agent and propylenediamine tetraacetic acid as complexant, and successive addition of sodium salt of N-methyl, N-cyclohexyl dithiocarbamate. The radiochemical purity of the complex was over 90%, as measured by thin layer chromatography. No decomposition of the complex at room temperature was observed over a period of 6 h. Its partition coefficient indicated that it was a lipophilic complex. The electrophoresis results showed that the complex was neutral. Biodistribution in mice showed that the complex accumulated in the heart and brain with high uptake. The heart/blood, heart/lung and brain/blood ratios were 5.55, 2.11 and 1.10, respectively, at 30 min post-injection, suggesting that this compound is a potential myocardial and cerebral imaging agent.     

Ester-modified TcO[SN(R)S/S] mixed ligand complexes: synthesis and preliminary evaluation

Two novel ^99mTc-(SNS/S) complexes: a mono-ester compound carrying an ethyl ester group on the tridentate ligand, ^99mTcO[C₂H₅OOCCH₂N(CH₂CH₂S)₂][SC₆H₄CH₃], 3, and a diester compound, carrying a second ethyl ester group on the monodentate ligand, ^99mTcO[C₂H₅OOCCH₂N(CH₂CH₂S)₂][SC₆H₄COOC₂H₅], 4, were synthesized. The corresponding oxorhenium(V) complexes, 1 and 2 were also synthesized. Enzymatic hydrolysis demonstrated that 3 remains intact after 10 min incubation while 4 is totally converted to an unidentified hydrophilic complex. Tissue distribution data in mice revealed that both complexes, 3 and 4, exhibit significant initial brain uptake (1.42 and 1.01% of injected dose at 5 minutes post injection respectively) and fast blood clearance.     

Dependency of the [18F]fluoromisonidazole uptake on oxygen delivery and tissue oxygenation in the porcine liver

We have previously shown that the accumulation of fluorine-18-labeled fluoromisonidazole ([¹⁸F]FMISO) is inversely correlated to tissue oxygenation, allowing the quantification of porcine liver tissue hypoxia in vivo. We determined the activity from administered [¹⁸F]FMISO in relation to the hepatic oxygen availability and the partial pressure of oxygen in tissue (tPO₂) to define a critical oxygen delivery on a regional basis. [¹⁸F]FMISO was injected 2 h after onset of regional liver hypoxia due to arterial occlusion of branches of the hepatic artery in 10 domestic pigs. During the experimental procedure the fractional concentration of inspired oxygen (FiO₂) was set to 0.67 in group A ( N=5) and to 0.21 in group B ( N=5) animals. Immediately before sacrifice, the tPO₂ was determined in normal flow and flow-impaired liver segments. The standardized uptake values (SUV) for [¹⁸F]FMISO was calculated from 659 single tissue samples obtained 3 h after injection of approximately 10 MBq/kg body weight [¹⁸F]FMISO and was compared with the regional total hepatic oxygen delivery (DO₂) calculated from the regional arterial and portal venous flow (based on ¹⁴¹Ce- and ^99mTc-microspheres measurements) and the oxygen content of the arterial and portal venous blood. In 121 tPO₂-measured liver tissue samples, the mean DO₂ was significantly decreased in occluded liver tissue samples [group A: 0.063 (0.044–0.089); group B: 0.046 (0.032–0.066)] compared to normal flow segments [group A: 0.177 (0.124–0.252); group B: 0.179 (0.128–0.25) mL·min⁻¹·g⁻¹; geometric mean (95% confidence limits); p < 0.01 in group A and p < 0.001 in group B]. The tPO₂ of occluded segments [group A: 5.1 (3.2–8.1); group B: 3.9 (2.4–6.2) mm Hg] was significantly decreased compared to normal flow segments [group A: 20.2 (12.6–32.5); group B: 22.4 (14.3–35.2) mm Hg; p < 0.01 in group A and p < 0.001 in group B]. Three hours after [¹⁸F]FMISO administration, the mean [¹⁸F]FMISO SUV determined in tPO₂-measured occluded segments was significantly higher [group A: 4.08 (3.12–5.34), group B: 5.43 (4.14–7.13)] compared to normal liver tissue [group A: 1.57 (1.2–2.06), group B: 1.5 (1.16–1.93); p < 0.001 for both groups]. The [¹⁸F]FMISO SUV allowed prediction of the tPO₂ with satisfying accuracy in hypoxic regions using the exponential regression curve { [¹⁸F]FMISO=1.05+6.7^{(−0.117 tPO₂}); r²=0.75;p < 0.001}. In addition, regardless of ventilation conditions, a significant exponential relationship between the DO₂ and the [¹⁸F]FMISO SUV was found ( r²=0.39,p < 0.001). Our results suggest that the reduction of the oxygen delivery below the critical range of 0.1–0.11 mL·min⁻¹·g⁻¹ regularly causes liver tissue hypoxia. The severity of hypoxia is reflected by the [¹⁸F]FMISO accumulation and allows the in vivo estimation of the tPO₂ in hypoxic regions.     

New renal function imaging agents. I. Synthesis and biological characterization of a [Tc]diaminomercapto(thio)ether (DAMTE)

The present study describes the synthesis of a [^99mTc]diaminomercapto(thio)ether (DAMTE-derivative) as a first compound of a new class of ^99mTc-complexes which is tubular excreted.

10-Benzoyl-8-keto-7-aza-2-amino-4,10-dithia-decanoic acid (CO₂-DAMTE 3) was synthesized by the reaction of succinimidyl-S-benzoyl-thioglycolate and (S)-2-aminoethyl- -cysteine. The respective technetium complex, ^99mTc---CO₂---DAMTE was obtained in radiochemical yields of about 70% using stannous chloride as reducing agent. Hydrolysis of the protecting group was performed either prior to the complexation of pertechnetate (“cold kit”) or during the labelling reaction (“hot kit”). Organ distribution was determined in Wistar rats. Within 24 h 40% of the activity were excreted into the feces and 43% into the urine, whereas 10% were retained in the kidneys. In contrast, a first human study showed a very fast renal elimination of ^99mTc---CO₂---DAMTE, a low liver uptake (< 10%) and no retention in the kidneys. The renal clearance of approx. 240 mL/min/1.73 m² in addition to the protein binding of > 95% suggests an effective tubular excretion of the compound.     

Facile synthesis of bis(hydroxamamide)-based tetradentate ligands for Tc-radiopharmaceutical

A facile, two-step synthesis of the bis(hydroxamamide)-based tetradentate ligands for ^99mTc-radiopharmaceuticals is described. Firstly, the hydroxamamide was converted to hydroximic acid chloride by reaction with sodium nitrite in hydrochloric acid at 0 °C. Secondly, treating the halide with the ethylenediamine or 1,3-propylenediamine in absolute ethanol formed the desired products, N,N′-ethylene bis(1-(4-nitroimidazole-1-yl)–propan-hydroxyiminoamide) (I) and N,N′-propylene bis(1-(4-nitroimidazole-1-yl)-propanhydroxyiminoamide) (II). The corresponding ^99mTc complexes showed high yields and were found by paper electrophoresis to be electrically neutral under physiological conditions. The partition coefficients indicated a distinct difference between the two complexes.     

The integrity of the disulfide bond in a cyclic somatostatin analog during tc complexation reactions

Recent development of a variety of thiol-free chelating agents has facilitated the design of ^99mTc-labeled somatostatin analogs suitable for receptor imaging of somatostatin-positive tumors. However, it remains ambiguous whether the disulfide bonds in cyclic peptides are stable during ^99mTc complexation reactions, and contradictory results have been reported regarding the integrity of disulfide bonds in cyclic somatostatin analogs. To estimate the stability of the disulfide bond in a synthetic somatostatin analog at low peptide concentrations, [¹²⁵I]I-RC-160, in which radioiodine was incorporated into the 3-Tyr residue, was synthesized and the integrity of the disulfide bond of the peptide was investigated in the presence of reducing agents such as ascorbic acid, dithionite, and stannous ions. The disulfide bond in [¹²⁵I]I-RC-160 remained stable in the presence of ascorbic acid in boiling water. The disulfide bond was also stable when treated with stannous ions at concentrations sufficient to reduce ^99mTc for complexation with a thiol-free chelating agent, bis(hydroxamamide) analog when the ^99mTc complexation reaction was performed at room temperature. However, the disulfide bond of [¹²⁵I]I-RC-160 was slightly cleaved in the presence of a small amount of stannous ions when the reaction was performed in boiling water. Treatment of [¹²⁵I]I-RC-160 with dithionite in boiling water markedly reduced the disulfide bond of the parental peptide. These findings indicated that synthetic somatostatin analogs may be labeled with ^99mTc with stannous ions as the reducing agent without impairing their structure after conjugation of thiol-free chelating agents that provide ^99mTc chelates under mild reaction conditions.     

The effect of cyclosporine-a on labeling blood cells with radiopharmaceuticals

The effect of cyclosporine-A (CsA) on the labeling efficiencies of red blood cells with reduced ^99mTcO₄⁻; leukocytes and platelets with ¹¹¹In oxine was studied. Blood was used from rats treated with CsA (30 mg/kg body weight) for 28 consecutive days and from control rats. For ^99mTc labeling of RBCs, blood was obtained from individual rats and in vitro labeling technique was used. For leukocyte and platelet labeling, blood was pooled from 5 rats either treated with CsA or control. Leukocytes/platelets were labeled with ¹¹¹In oxine using routine techniques. The labeling efficiency for ^99mTc RBCs was 83.42 ± 0.83% (CsA treated) and 84.85 ± 0.62% (control); ¹¹¹In-oxine leukocytes was 38.5 ± 1.75% (CsA treated) and 42.5 ± 3.53% (control); and for ¹¹¹In-oxine platelets, it was 74.0 ± 2.5% (CsA treated) and 78.0 ± 1.41% (control). Comparison of the results indicate that there is no difference between the percent labeling efficiencies of ^99mTc RBCs, ¹¹¹In-oxine leukocytes, and ¹¹¹In-oxine platelets for CsA-treated and control rats. Hence, CsA does not interfere with the labeling process of blood cells with radiopharmaceuticals.     

Lowering of pI by acylation improves the renal uptake of Tc-labeled anti-Tac dsFv: effect of different acylating reagents

Anti-Tac disulfide-stabilized variable region fragment (dsFv) was labeled with ^99mTc by a preformed chelate approach using ^99mTc-MAG3-trifluorophenyl (TFP) ester. Simultaneously it was acylated with TFP-lactate or succinic anhydride to decrease the isoelectric point of dsFv (pI 10). Acylation of dsFv (0.04 mM) with the lactate at a 73 times molar excess reduced the pI to 5.0–6.7, whereas acylation with succinic anhydride at a 30 times molar excess reduced the pI to 4.9–8.7. Comparative biodistribution studies performed in mice (n = 5) showed the reduced renal accumulation of the ^99mTc proportional to the pI reduction. The effect of the pI on the reduced renal uptake was especially pronounced at 15 min postinjection. The reduced renal uptake was also reflected in the reduced whole-body retention, indicating that lowering the pI inhibited the tubular reabsorption of the labeled dsFv.     

The labelling of Nanocoll with [In] for dual-isotope scanning

Visualization and biopsy of sentinel lymph nodes play an important role in planning and controlling the therapy of breast cancer. Hitherto two methods—scintigraphy or gamma probe detection after injection of [^99mTc]-nanocolloids and visual detection after injection of patent blue dye—are used routinely. There are no conclusive publications elucidating such important parameters as injection site, injection method and colloidal parameters. The present work aims to label Nanocoll^® with [¹¹¹In] to provide an alternative method, a simultanous one-compound dual-isotope application.

Methods: [¹¹¹In]-Indiumchloride was buffered with acetate and transferred to the nanocolloid. The colloid labelling reaction was complete after 30 min and filtrated through 100 nm Nuclepore^® filters.

Results: Incorporation yield of [¹¹¹In]-Indium into the nanocolloid was nearly quantitative, the step associated with the major loss of activity was the particle sizing with a mean yield of 55%.

Conclusion: The presented method allows for the routine supply of [¹¹¹In]-nanocolloids. Size-filtered [¹¹¹In]-Nanocoll^® shows the same particle size range as [^99mTc]-Nanocoll^®.     

Synthesis of a F-18 labeled analog of antitumor prostaglandin Δ-pGA1 methyl ester using p-[F]Fluorobenzylamine

A fluorine-18 labeled analog of an antitumor prostaglandin Δ⁷-PGA₁ methyl ester, 15-deoxy-13,14-dihydro-Δ⁷-PGA₁ 4-[¹⁸F]fluorobenzyl amide ([¹⁸F]3), was synthesized as a tracer candidate for detecting tumors with positron emission tomography. p-[¹⁸F]Fluorobenzylamine (p-[¹⁸F]FBnA) used as a labeled precursor for the synthesis of [¹⁸F]3 was prepared by fluorination of a 4-N, N, N-trimethylammoniumbenzonitrile triflate with [¹⁸F]fluoride and subsequent reduction with borane-dimethylsulfide. Radiochemical yield and purity of p-[¹⁸F]FBnA obtained were 39–49% (decay uncorrected) and 91–96%, respectively, after C18 Sep-Pak purification. Treatment of p-[¹⁸F]FBnA with a 15-deoxy-13,14-dihydro-Δ⁷-PGA₁ N-succinimidyl ester in acetonitrile and subsequent HPLC purification gave radiochemically pure (>99%) [¹⁸F]3 with a 58% decay uncorrected yield. The total synthesis time was 70 min from the start of the radiosynthesis of p-[¹⁸F]FBnA.     

Biodistribution studies of Tc-labeled myoblasts in a murine model of muscular dystrophy

The purpose of this study was twofold: first, to evaluate the myoblast labeling of various ^99mTc complexes and to select the complex that best accomplishes this labeling, and second to evaluate the biodistribution of myoblasts labeled with this complex using mice with MDX muscular dystrophy (the murine homologue of Duchenne’s muscular dystrophy). The following ligands were used to prepare the corresponding ^99mTc complexes: hexakis-methoxy-isobutyl-isonitrile (MIBI), bis(2-ethoxyethyl)diphosphinoethane (Tf), (RR,SS)-4,8-diaza-3,6,6,9-tetramethyl-undecane-2,10-dione-bisoxime (HM-PAO), bis(N-ethyl)dithiocarbamate (NEt), and bis(N-ethoxy, N-ethyl)dithiocarbamate (NOEt).

One million murine myoblasts were incubated for 30–60 minutes with 5 mCi of each of the 99mTc complexes prepared from the above ligands. Viability was assessed by microscopic counting after trypan blue staining, and the radioactivity absorbed in the cells was measured after centrifugation. The compound with the highest uptake in cellular pellets was [^99mTc]N-NOEt. The biodistribution of myoblasts labeled with this complex was evaluated after intraaortic injection in dystrophic mice. Such an approach has the potential of effecting widespread gene transfer through the bloodstream to muscles lacking dystrophin.     

Dose-dependent biodistribution of [(99m)Tc]DTPA-mannosyl-dextran for breast cancer sentinel lymph node mapping

[^99mTc]DTPA-mannosyl-dextran is a receptor-binding radiopharmaceutical specifically designed for sentinel lymph node mapping. The purpose of this study was to test the biodistribution and safety of [^99mTc]DTPA-mannosyl-Dextran at different molar doses. Twenty-four female breast cancer patients participated in this study. Four groups of 6 patients received an injection of 0.2, 1.0, or 5.0 nmol of [^99mTc]DTPA-mannosyl-Dextran or filtered [^99mTc]sulfur colloid. The injection site clearance was monitored by dynamic imaging for three hours. Whole body scans were acquired at 2.5 and 12, and lymph nodes were assayed for radioactivity after gamma-guided sentinel lymph node biopsy. Injection site clearance of [^99mTc]DTPA-mannosyl-Dextran was not statistically different in a dose-dependent manner. Dose-dependent sentinel node uptake was observed (p = 0.03). There were no clinically significant alterations in laboratory parameters among all dose levels at 4 h or 24 h post injection compared to preoperative levels. Radiation absorbed doses did not differ among the three dose levels, but were lower than filtered [^99mTc]sulfur colloid.     

Use of 99mTc-mononuclear leukocyte scintigraphy in nosocomial fever

Purpose: To determine the overall diagnostic accuracy of mononuclear leukocyte- ^99mTc scintigraphy in the routine detection of infectious lesions and fever of unknown origin (FUO) in inpatients.

Material and Methods: The use of mononuclear leukocyte ^99mTc scintigraphy is presented in 87 patients who fulfilled the Durack and Street diagnostic criteria of nosocomial FUO; 66 patients were suspected of having infectious lesions (myocarditis, endocarditis, infected catheters, diabetic foot, and osteomyelitis) and 21 patients presented with unknown causes of FUO. Scans were carried out 1, 3, and 24 h after injection of labeled leukocytes.

Results: In three cases (3/27) where scintigraphs were negative, biopsies were positive. There were two (2/87) false-positive scintigrams. We found a 95.8% sensitivity and 92.3% specificity. PPV was 93.8%, PPN 94.7%, and accuracy 94.2%.

Conclusion: Mononuclear leukocyte ^99mTc scintigraphy showed high sensitivity, specificity, positive and negative predictive values in patients with nosocomial FUO. These results suggest an important role for nuclear medicine in the management of patients with infection/inflammation.     

Uptake of Tc tetrofosmin in lymphoma cell lines: a comparative study with Tc sestamibi

Technetium-99m (^99mTc) tetrofosmin has been used as a tumor-seeking agent. However, its role in detecting lymphomas has not been widely investigated. The aim of the present study was to determine the uptake and clearance characteristics of ^99mTc tetrofosmin in lymphoma cell lines. ^99mTc sestamibi was also evaluated for comparison. Three lymphoma cell lines (U-937: monocyte-like, histiocytic lymphoma, human; RAMOS: B-lymphoma cell line, American Burkitt lymphoma, lymphoblastoid, human; Hs445: Hodgkin's disease, lymphoid, human) were studied. After incubation of radiotracers ^99mTc tetrofosmin and ^99mTc sestamibi in medium for 0, 10, 20, 30, 60, 120 and 180 min, the uptake and clearance of each radiotracer were measured in the three lymphoma cell lines. The uptake of ^99mTc tetrofosmin was lower than that of ^99mTc sestamibi in these lymphoma cell lines. Among the three cell lines, Hs445 showed the greatest ^99mTc tetrofosmin uptake capacity. RAMOS and U-937 showed similar ^99mTc tetrofosmin uptake capacities. ^99mTc tetrofosmin accumulated in the three tested lymphoma cell lines, especially in the Hodgkin's disease cell line. However, in comparison with ^99mTc sestamibi, ^99mTc tetrofosmin may not be the best radiotracer for detection of lymphoma.