Evaluation of novel cationic 99mTc(I)-tricarbonyl complexes as potential radiotracers for myocardial perfusion imaging

This report describes the evaluation of three cationic ^99mTc(I)–tricarbonyl complexes — [^99mTc(CO)₃(L)]⁺ (L=N-methoxyethyl-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (ME-PNP), N-[15-crown-5)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (15C5-PNP) and N-[18-crown-6)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (18C6-PNP)) — as potential radiotracers for myocardial perfusion imaging. Biodistribution, imaging and metabolism studies were performed using Sprague–Dawley rats. It was found that bisphosphine ligands have a significant impact on the biodistribution characteristics and clearance kinetics of their cationic ^99mTc(I)–tricarbonyl complexes. Among the three radiotracers evaluated in this study, [^99mTc(CO)₃(15C5-PNP)]⁺ has a very high initial heart uptake and is retained in the rat myocardium for >2 h. It also shows rapid clearance from the liver and lungs. The heart/liver ratio of [^99mTc(CO)₃(15C5-PNP)]⁺ is 2.5 times better than that of ^99mTc-sestamibi at 30 min postinjection. [^99mTc(CO)₃(15C5-PNP)]⁺ is almost identical to ^99mTcN-DBODC5 with respect to heart uptake, heart/lung ratio and heart/liver ratio. Results from metabolism studies show that there is no significant metabolism for [^99mTc(CO)₃(15C5-PNP)]⁺ in the urine, but it does show a small metabolite peak (<10%) in the radio high-performance liquid chromatography chromatogram of the feces sample at 120 min postinjection. Results planar imaging studies demonstrate that [^99mTc(CO)₃(15C5-PNP)]⁺ has a much better liver clearance profile than ^99mTc-sestamibi and might give clinically useful images of the heart as early as 30 min postinjection. [^99mTc(CO)₃(15C5-PNP)]⁺ is a very promising candidate for more preclinical evaluations in various animal models.     

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.     

A solid-phase technique for preparation of no-carrier-added technetium-99m radiopharmaceuticals: application to the streptavidin/biotin system

A high effective specific activity (HESA) formulation of a biotin-containing ^99mTc ligand [RP488: dimethyl-Gly-Ser-Cys(Acm)-Lys(Biotin)-Gly] conveniently prepared from solid phase was compared to a typical low effective specific activity (LESA) solution formulation to demonstrate improved targeting to streptavidin in an in vitro assay and in an in vivo rat model. RP488 was coupled to a maleimide-functionalized polyethylene glycol resin via a thiol ether linkage and labeled with ^99mTc-gluconate at room temperature, followed by elution of the HESA ^99mTc-RP488 in saline (minimum specific activity 1000 TBq/mmol by amino acid analysis). Both HESA and LESA ^99mTc-RP488 labeled at > 90% purity. In vitro, HESA ^99mTc-RP488 incubated with streptavidin-agarose was bound quantitatively, but there was competition from addition of increasing amounts of cold RP488. In rats, radiotracer uptake was evident at the site of implantation of streptavidin-agarose beads for the HESA dose, less uptake of low effective specific activity (LESA) material, and no appreciable uptake in the control rats of the LESA or HESA dose. The target-to-background ratio for HESA ^99mTc-RP488 was 5.4 times that of the control. The solid-phase technology offers a convenient way to prepare high specific activity receptor-targeting ^99mTc radiopharmaceuticals.     

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.     

Calibration of a radionuclide calibrator system as a Bulgarian standard for activity

A commercially available radionuclide calibrator of the type Curiementor 3 (PTW, Freiburg, Germany) was calibrated using activity standard solutions, from the Physikalisch-Technische Bundesanstalt (PTB), of a number of photon-emitting radionuclides, in particular those used in nuclear medicine: ¹⁸F, ⁵¹Cr, ⁶⁷Ga, ^99mTc, ¹¹¹In, ¹²³I, ¹²⁵I, ¹³¹I, ¹⁸⁶Re, ²⁰¹Tl, and for beta-emitting nuclides: ³²P, ⁸⁹Sr, ⁹⁰Y, ²⁰⁴Tl. An energy-dependent efficiency curve was established to calculate efficiencies for photon-emitting radionuclides. The differences between experimental and calculated radionuclide efficiencies of the measuring system are of the order of a few percent. The performance of the system was checked for instrument stability, using a long-lived ¹³⁷Cs source, and for linearity using the decay of a ^99mTc source. The calibration measurements were carried out with 2 g of solution in standard PTB-type glass ampoules. The dependence of efficiency with varying solution mass and changing ampoule geometry is studied for some of the radionuclides. For example, geometry correction factors are determined for various solution volumes or ampoules with different wall thickness. The measuring system will enable the National Centre of Metrology (NCM) of Bulgaria to provide calibration services for activity measurements, which are traceable to PTB standards, and to organize national comparisons in order to improve the quality of measurements for nuclear medicine in Bulgarian hospitals. Furthermore, it should enable NCM to declare Calibration and Measurement Capabilities (CMCs) and to submit radioactive solutions to the International Reference System (SIR) at the BIPM in order to compare the results with Key Comparison Reference Values (KCRVs).     

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.     

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.     

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.     

Quality audit programme for Tc and I radioactivity measurements with radionuclide calibrators

The use of radiopharmaceuticals in nuclear medicine for diagnosis and therapy has increased over the years with ^99mTc and ¹³¹I being most widely used. Quality audit programmes for radioactivity measurements of ¹³¹I have been ongoing and the 12th audit was recently conducted among seventy nuclear medicine centres (NMC) in India. An audit for the activity measurements of ^99mTc was conducted for the first time among ten NMCs in Mumbai, India. These programmes for radioactivity measurements have become very important to establish traceability of measurements to national and international standards and ensure accurate calibration of radionuclide calibrators. The results of both the audits are very encouraging. Ninety-four percent of the NMCs for ¹³¹I activity measurements were within a window of ±10% and for ^99mTc one NMC was deviating more than ±10%. The methodology adopted for the audit and results are discussed in detail in this paper.     

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.     

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.     

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.     

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^®.     

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.     

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.     

Tc-99m and Re-186 complexes of tetraphosphonate ligands and their biodistribution pattern in animal models

The syntheses of four alpha-aminomethyl phosphonates and their complexation studies with (99m)Tc and (186/188)Re are reported. Complexation conditions were standardized to give maximum yields, which ranged from 90-97%. The yields of complexation were estimated by paper chromatography. The (99m)Tc complexes were stable for more than 4 h, while the (186/188)Re complexes were stable for 3-8 days when stored at 4 degrees C. Biodistribution of these complexes in Wistar rats were carried out, and the uptake in bone and other soft tissue are detailed. Bone uptake of the (99m)Tc complexes varied from 40-60% at 30 min postinjection depending on the ligands. The uptake in soft tissue was minimum with all the complexes. A comparison of the biodistribution studies of the (99m)Tc complexes with that of the well-established radiopharmaceutical (99m)Tc-MDP was carried out for the purpose of evaluating the efficacy of the radiopharmaceutical preparation with the complexes of these ligands. The bone uptake of the (186/188)Re complexes varied from 19-28% corresponding to 1.6-3% per g at 3 h postinjection. The residual activity in both (99m)Tc and (186/188)Re complexes showed renal clearance.     

Role of scintigraphy with technetium-99m depreotide in the diagnosis and management of patients with suspected lung cancer

Background: In Sweden, there are over 3000 new lung cancer cases every year. There are still numerous patients with undetermined lesions after routine diagnostic evaluation by clinical examination, chest radiography, computed tomography (CT) of the thorax, and bronchoscopy. An appropriate method for further diagnostic workup is therefore needed.

Purpose: To evaluate the diagnostic value of the somatostatin analogue depreotide in patients with suspected lung cancer, and to determine in which clinical settings it would be beneficial to use ^99mTc-depreotide scintigraphy.

Material and Methods: We included 99 consecutive patients referred to our hospital with suspected lung cancer. A clinical examination, bronchoscopy, chest radiography, CT of the thorax and upper abdomen, and scintigraphy were done. Scintigraphy was performed after injection of 740 MBq ^99mTc depreotide with tomographical imaging of the thorax and whole-body scanning. The diagnostic outcome of the scintigrams was compared to CT, using morphology or clinical outcome as the endpoint.

Results: ^99mTc-depreotide uptake was found in 62 out of 66 malignancies, including 57 of 58 primary lung cancer cases. Two cases of lung metastasis (one from a colon cancer and one from an adenoid cystic carcinoma originating in the palate) and one rib chondrosarcoma did not show depreotide uptake. There were 33 patients with benign lesions, of whom 16 displayed false-positive ^99mTc-depreotide uptake, whereof 11 were pneumonias. Tc-99m-depreotide uptake was absent in 17 patients with benign lesions, including all 10 hamartomas. The sensitivity in detecting malignancy was 94%, and in detecting lung cancer 98%. The specificity was calculated based on two sets of data. When all cases were used, the specificity was 52%. If the 12 pneumonias are excluded, the specificity was 77%.

Conclusion: ^99mTc-depreotide scintigraphy has a high sensitivity in detecting lung cancer. The method is useful in decision-making with respect to surgery.     

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.     

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.     

Experimental studies on the proton-induced activation reactions of molybdenum in the energy range 22–67 MeV

The production cross-sections of ^99,93mMo, ^96,95,95m,94Tc, ^96,95,92m,90Nb, ^89,88,86Zr and ^88,87,86Y radionuclides for proton-induced reactions on molybdenum were measured with molybdenum targets of natural isotopic composition using a stacked-foil activation technique in the energy range 22–67 MeV. The thick target integral yields were also deduced for each reaction using the measured cross-sections from the respective threshold up to 67 MeV. The results have given new data for all of the investigated radionuclides. The results of the present experiment showed excellent agreement with the earlier reported data in the lower energy region.