J. J. P. de Lima

Structural and in vivo studies of metal chelates of Ga(III) relevant to biomedical imaging.

The solution chemistry and structure of the complex of the triazamacrocyclic ligand NOTP (1,4,7-triazacyclononane-1,4,7-tris(methylenephosphonate)) with Ga3+ in D2O have been investigated by 1H, 71Ga and 31P NMR spectroscopy. These NMR results show the presence of a 1:1 Ga(NOTP)3- complex, with a highly symmetrical, pseudo-octahedral geometry, possibly with a C3 axis. The 1H spectrum shows that the triazamacrocyclic chelate ring is very rigid, with all the ring protons non-equivalent. The complex is stable in aqueous solution in a wide pH range. Its high thermodynamic stability agrees well with previous results from biodistribution and gamma imaging studies in Wistar rats with 67Ga3+ chelates of triaza macrocyclic ligands, which showed that the neutral chelates 67Ga(NOTA) (where NOTA is 1,4,7-triazacyclononane-1,4,7-triacetate) and 67Ga(NOTPME) (where NOTPME is 1,4,7-triazacyclononane-1,4,7-tris(methylenephosphonate monoethylester)) have similar in vivo behaviour, with high stability and rapid renal excretion, but the high negatively charged 67Ga(NOTP)3- has a considerably slower kidney uptake and elimination.

Cardiac lymphatic dynamics after ischemia and reperfusion—experimental model

ABSTRACT. The aim of the present study was to investigate the lymphatic cardiac circulation in an experimental model of ischemia plus reperfusion in mongrel dogs (Canis familiaris L). As radiotracer we used 0.2-0.25 ml (111 MBq) of 99mTc-Re2S7 colloid (+/-10 microm), injected subcapsullary below the second diagonal of the descending anterior ligated coronary artery with a special needle. A gamma-camera/Starport + DecStation were used for data acquisition. Four experimental groups with five animals each were established: G I = controls; G II = immediately after acute myocardial infarction (AMI); G III = late infarction (5 days after AMI); G IV = ischemia (90 min) + reperfusion. Four regions of interest (ROIs) were chosen: injection area (ZA), above (ZB), near right (ZD), and far right (ZC) from ZA. Mean disappearance times in ZA and dynamic parameters in the other ROIs were determined from activity/time curves drawn in each area, using homemade software. The results obtained seem to indicate that the methodology is appropriate to a detailed study of lymphatic drainage in pathological situations in animal models.

153Sm3+ and 111In3+ DTPA derivatives with high hepatic specificity: in vivo and in vitro studies

Abstract Two DTPA derivatives, a mono-amide derivative containing an iodinated synthon, DTPA-IOPsp (L 1 ) and the ligand DTPA(BOM) 3 (BOM=benzyloxymethyl) (L 2 ), radiolabelled with 153 Sm 3+ and 111 In 3+ , were studied as potential hepatospecific gamma scintigraphic agents. In vivo studies with Wistar rats show that the main excretory pathway for all the chelates studied is the hepatobiliary system. The complexes of L 2 show even greater hepatobiliary specificity than L 1 , perhaps as a consequence of longer blood circulation times due to their strong affinity towards HSA. The 153 Sm 3+ chelates are also more hepatospecific than the corresponding 111 In 3+ chelates. The La 3+ and In 3+ chelates of L 1 and L 2 show some structural and dynamic differences in aqueous solution, as studied by 1 H NMR spectroscopy. While only two nona-coordinated isomers were observed for the La 3+ complexes with both ligands, its number is much larger in the In 3+ complexes, with both octa- and hepta-coordinated species (with unbound side arms), as well as structural isomers for each coordination number.

Characterization of 111In3+ complexes of DTPA amide derivatives: biodistribution and clearance studied by gamma imaging

A large series of structurally related diethylenetriaminepentaacetic acid amide derivatives with different structures and lipophilic properties were synthesized and radiolabeled with (111)In(3+). Two of the more hydrophobic compounds studied ([(111)In]L(9) and [(111)In]L(10)) showed high affinity for human serum albumin (HSA). The biodistribution and clearance properties shown by all complexes upon injection in Wistar rats were followed by gamma imaging. The blood retention time of the chelates correlates better with their binding to HSA than with their hydrophilic/lipophilic ratio. Hydrophilic and negatively charged complexes undergo renal retention, while the majority of the lipophilic complexes are retained in the blood for a longer period of time and are cleared through the liver.

Ventilation and perfusion display in a single image

A new method of ventilation and perfusion display onto a single image is presented. From the data on regions of interest of the lungs, three-dimensional histograms are created, containing as parameters X and Y for the position of the pixels, Z for the perfusion and colour for local ventilation. The perfusion value is supplied by sets of curves having Z proportional to the local perfusion count rate. Ventilation modulates colour. Four perspective views of the histogram are simultaneously displayed to allow visualization of the entire organ. Information about the normal ranges for both ventilation and perfusion is also provided in the histograms.

Dependence of an individual renogram on the other kidney through the blood activity, shown by convolution

In the renal studies with 131I-Hippuran the blood concentration of the radiocompound is the input for both of the kidneys. A renogram is the response of a kidney to such an input. Since the blood activity depends on the total clearance of 1311-Hippuran f rom the blood, the input function to each kidney depends on the functional state of its pair. Consequently each individual renogram is expected to be influenced by the other kidney through the blood activity. Deconvolution methods applied to the renogram curves and to the blood activity [1, 2, 3, 4] have shown typical retention functions, which are the response functions to instantaneous injections in the renal artery, for both normal and abnormal kidneys. A retention function is specific for a kidney for a particular hydration state of the patient and it is not dependent on the functional state of the second kidney. Deconvolution gives the retention functions, characteristic of the kidneys whatever the input functions, even in situations of poor injection [1]. Although having some advantages the deconvoluted curves are not widely used in renal studies. The renogram curves with the advantage of being directly obtained are generally prefered. Perhaps the interest of the deconvoluted curves is emphasized if one shows how noticeable the differences in the renogram curves of a particular kidney can be for different blood activity input functions resulting f rom different functional states of the second kidney. Let us compare two situations in which two kidneys with the same functional state are the pairs of kidneys with very different functional behaviours. These could be the cases of two patients, the first one supposed to have the right kidney with an abnormal retention function R and the left kidney with a normal retention function L1; the second patient LI

Renal gammagraphy with 99mTc-phosphomycin

Abstract99mTc-Phosphomycin, a new radiopharmaceutical for kidney visualization, was used for animal experiments and tests of 171 patients. The results confirmed the usefulness of this product. The ease and yield of the labelling procedure, the low cost of the product, the excellent quality of the images and the functional information obtained showed that the use of 99mTc-phosphomycin as a radiopharmaceutical for kidney visualization has many advantages.

Visualização da Rede Linfática Pulmonar Profunda usando Radioliposomas

Deep lymphatic drainage plays an important role in the lung, as it removes foreign materials laying on the airways surface, such as pathogenic microorganisms. This drainage is also associated with lung tumour dissemination route. Liposomes with a specially tailored membrane were used as foreign particles to be removed by the lung lymphatics. We aim to obtain images of deep lung lymphatics in baboons using liposomes encapsulating (99m)Tc-HMPAO, as aerosols. Axillary lymph nodes were visualized 30 min post-inhalation, becoming more evident 1 hour after, when abdominal aortic and inguinal lymph nodes were also observed. Late images added no additional information. ROIs and their time-activity curves were drawn to obtain biokinetic information. In conclusion, we can say that the proposed technique enables visualization of the deep lymphatic lung network and lymph nodes. This methodology may be an important tool for targeted lung delivery of cytotoxic drugs.

First pass evaluation of blood velocity in the pulmonary artery

Studying the kinetics of blood flow in the pulmonary artery using non-invasive techniques may be an important tool in assessing the prognosis of lung diseases. The aim of this study was to ascertain dynamic parameters of pulmonary blood flow, particularly the velocity of a small bolus of a radioactive tracer after intravenous injection. Since the shape and distribution pattern of the bolus changes substantially from frame to frame, common image processing techniques for motion detection or other techniques, such as accumulation of subtracted images, segmentation and spectral analysis with temporal/spatial filtering, are unable to properly evaluate the motion of the bolus. However, the passage of the bolus from the arm to the lungs was visualized with good contrast through acquisition of a first pass sequence of scintigraphic images. The wave form of the bolus becomes increasingly complex as it progresses towards the pulmonary artery. In the proposed method the time-activity curves for each pixel are displayed. It is assumed that the peaks of the maximum counts in these curves correlate with the time after injection that the bolus takes to cross each pixel (bolus head). The bolus head contains information on time, space and activity, and allows the velocity of the studied fluid to be calculated. We demonstrated a mean velocity through the pulmonary artery trunk in resting patients of approximately 11 cm/s, with a mean residence time of 0.5 s.

Visualization of deep lung lymphatic network using radioliposomes

Abstract Deep lymphatic drainage plays an important role in the lung, as it removes foreign materials laying on the airways surface, such as pathogenic microorganisms. This drainage is also associated with lung tumour dissemination route. Liposomes with a specially tailored membrane were used as foreign particles to be removed by the lung lymphatics. We aim to obtain images of deep lung lymphatics in baboons using liposomes encapsulating 99mTc-HMPAO, as aerosols. Axillary lymph nodes were visualized 30 min post-inhalation, becoming more evident 1 hour after, when abdominal aortic and inguinal lymph nodes were also observed. Late images added no additional information. ROIs and their time-activity curves were drawn to obtain biokinetic information. In conclusion, we can say that the proposed technique enables visualization of the deep lymphatic lung network and lymph nodes. This methodology may be an important tool for targeted lung delivery of cytotoxic drugs.