Journal of nuclear biology and medicine (Turin, Italy : 1991)最新文献

Gentamicin is an aminoglycoside antibiotic used to treat a wide variety of infections caused by gram-negative organisms, but it is potentially toxic to the kidneys. Due to its nephrotoxicity, gentamicin may cause abnormal renal uptake to be seen on 99mTc-MDP bone scintigraphy. The presence of the radiopharmaceutical in the kidneys, along with an increase in renal retention, tend to produce scintigraphic results that falsely identify characteristics related to diseases such as renal vascular, or urinary tract obstruction, and even renal cancer. An altered biodistribution may provide misleading information that can either mask or mimic certain disease symptoms. A method to maximize the therapeutic benefit of gentamicin while minimizing the risk of nephrotoxicity and the appearance of a hot kidney on scintigraphy is desirable. Serial pharmacokinetic dosing has been proposed as a method to accomplish this goal. Therapeutic drug monitoring (TDM) of gentamicin therapy, and bone scintigraphy employing 99mTc-MDP as the radiopharmaceutical was carried out in 22 patients. The data presented here demonstrate that with serial pharmacokinetic dosing of gentamicin, the iatrogenic alteration caused by gentamicin therapy can be avoided.

Bleomycin (BLM) is a well known natural antibiotic. It is toxic to dividing cells and has been used for the treatment of several forms of cancer. BLM has been labeled with various cations, but most of them have turned out be unstable in in-vivo experiments. In-BLM demonstrated high bone marrow uptake, but using 111In-bleomycin complex (BLMC) formed at low pH, the low in vivo stability and high bone marrow seeking behavior of the molecule could be avoided. The idea of using BLMC in combined radiotherapy and chemotherapy is intriguing. In this study we examined the effects of 111In-A'2a-c-BLMC in the treatment of 31 head and neck cancer patients. Findings were compared with those of surgery, and pre-operative radiology. The injected activity was 85-110 MBq, and the specific activity was approximately 100 MBq/mg. The half-life of 111In activity in serum varied from 1.5 to 3.1 hours. Maximum activity in the urine was achieved in all patients within 3 hours, and the average half-life in urine was 2 hours. In most patients 50% was excreted within 3 hours, in some 70%; in all patients > 95% of the activity was excreted within 22 hours. In surgical samples from 24 patients the best tumor-to-tissue ratios were: fat 60:1, bone 17:1, muscle 12:1, blood 3.6:1. All patients were examined on the injection day with ultrasonography of the neck. Using 111In-BLMC we missed a few small lymph nodes in 2 patients, but there were no false positive findings.(ABSTRACT TRUNCATED AT 250 WORDS)

The possibility of using 99mTc-labelled nucleotides as tumour seeking agents has been proposed by different research groups. We have recently reported the preparation of a 99mTc-ADP complex with a high radiochemical purity (> 95%), good in vitro and in vivo stability and promising biodistribution results when injected in mice bearing spontaneous mammary adenocarcinomas. Here we report the results of further investigations in animals with spontaneous neoplastic processes, including whole-body autoradiography in mice (20 minutes and 60 minutes post injection) and gamma-camera imaging studies in Wistar rats. Dynamic studies (up to 45 minutes) and static images (up to 18 hours) were acquired to determine the pharmacokinetics of 99mTc-ADP and the tumour/muscle and tumour/blood ratios. Blood-pool studies were also performed as a control. Tumours were visualized by autoradiography as was to be expected from the biodistribution studies. Dynamic studies showed a rapid blood clearance and a behaviour that fitted to a tricompartimental model. Radioactivity was rapidly taken up by the kidneys and excreted in the urine. No evidence of in vivo instability of the complex was observed. Tumour uptake reached the maximum values after 20 minutes post-injection. Tumour/blood and tumour/muscle ratios improved over time, enhancing tumour visualization. The best images were obtained after 3 hours post injection. In summary, our studies suggest that 99mTc-ADP is a promising radiopharmaceutical for tumour diagnosis.

The Fab fragment of a mouse monoclonal antibody AM(3-48) that recognizes alpha and beta-heavy chains of human atrial and ventricular myosin and beta-heavy chain of human slow skeletal muscle myosin [CardioVisionTM] was labeled with 99mTc using stannous reductant in a simple, instant kit method. The infarcted heart uptake in dogs of 99mTc-AM(3-48)Fab' was compared with that of established radiopharmaceuticals routinely used for cardiac imaging in humans. The dog infarct was induced by bringing a catheter from the femoral artery to the coronary artery where an artificial blood clot was generated. The 99mTc-AM(3-48)Fab' preparation was selectively taken up by infarcted myocardium, resulting in diagnostic quality images of the infarcted area as early as 6 hour post-injection, rendering CardioVisionTM particularly useful for SPECT imaging. Good agreement was found between the images obtained with 99mTc-Pyrophosphate and those obtained with 99mTc-AM(3-48)Fab', while the infarcted area was clearly delineated as a cold spot with 99mTc-MIBI or 201 Tl-thallous chloride. The biodistribution of 99mTc-AM(3-48)Fab' was also studied in healthy and isoproterenol-infarcted rats, from which dosimetry values in man were extrapolated. The data indicate that the kidneys will receive the highest radiation dose and that they will be the main contributors to the total radiation burden, which was estimated at 0.005 rad/mCi.

The anti-colon carcinoma MoAb35 and its F(ab')2 fragment were labelled with 131I or 67Cu and their biodistributions compared in nude mice bearing human tumour xenografts. Two-fold higher levels of 67Cu were found in the xenografts than 131I, with no significant difference in whole-body distribution. For the F(ab')2 fragment tumour levels were not significantly different between 131I and 67Cu. A very high accumulation of 67Cu was found in the kidney (36.7% ID/g). Whether deiodination in the kidney could account for the difference in nuclide accumulation was checked by repeating the study with 131I, linked to the F(ab')2 by a method known to resist deiodination. The results showed a slight increase in tumour accumulation of 131I but kidney levels remained low at 3.1% ID/g 24 hours post-injection compared to 42.4% ID/g for 67Cu, suggesting that deiodination does not play a role in the observed low levels of 131I in the kidney. Ongoing studies on the distribution and processing of radioimmunoconjugates will hopefully assist in their application in clinical studies.

A system aimed at the management and fusion of multimodal biomedical images, including X-ray computed tomography, magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography, has been implemented for neurological applications. This bioimaging integration system (BIS) consists of a network for image transmission from acquisition machines to dedicated image processing workstations, a software library for image standardization, and an image registration technique to project multimodal volumetric images into a common reference space. The registration procedure was evaluated in MRI/PET correlation studies, in which misalignment errors of 2.6 mm in the xy transaxial plane and 3.4 mm along the z axis were found. BIS has been validated for the anatomical-functional correlation analysis of MRI and PET images in neurological research protocols and clinical studies.

The hydrophilic penta-anionic complex [Technetium (Carboxymethylisocyanide)6]-5, [Tc(CNCH2COO-)6]-5 (Tc-CAMI) was synthesized to evaluate its potential as a renal function imaging agent. The compound contains six distally arranged carboxyl groups that can act as substrates for the organic acid receptor of the renal cell to effect tubular secretion of this agent. Dynamic gamma-camera imaging of 99mTc-CAMI was performed in normal dogs to compare its bio-distribution and pharmacokinetics with those of proven tubular secretion (99mTc-MAG3) and globular filtration (99mTc-DTPA) agents. The relative difference between the observed mean renal transit times (MRTT) of 99mTc-CAMI and 99mTc-MAG3 was 0.15 compared with 1.24 for 99mTc-CAMI and 99mTc-DTPA. Pathological models of obstructive uropathy, renal arterial stenosis and renal denervation were produced in the same animals to demonstrate the diagnostic potential of the agent. These experiments and data showing that probenecid competes with 99mTc-CAMI for renal transport indicate that this compound functions as a tubular secretion agent and may be useful for monitoring renal function in various disease states.

Copper (II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) (Cu-PTSM) labelled with 62Cu or 64Cu is currently under investigation as a radiotracer for imaging the distribution of blood flow with positron emission tomography (PET). The application of a simple trapped tracer model in conjunction with tissue uptake and continuous arterial sampling to estimate blood flow has been compared with the 57Co-microsphere method in the rat. After intraventricular injection the cumulative arterial function for 64Cu increased progressively due to the presence of circulating non lipophilic complexes. The cumulative function for lipophilic 64Cu-PTSM extracted in n-octanol plateaued at levels corresponding to those reached by 57Co-microspheres. No consistent disagreement was found between cardiac output and blood flow estimated by 64Cu-PTSM and 57Co-microspheres in low to moderate flow tissues: muscle (0.08, 0.07 mL/min/g; 64Cu mean, 57Co mean), brain (0.52, 0.43 mL/min/g) and kidney (2.29, 2.45 mL/min/g). However, 64Cu-PTSM underestimated blood flow measured by 57Co-microspheres in myocardium (4.09, 6.55 mL/min/g). A simple tissue trapping model may therefore be suitable for the derivation of blood flow estimates in low to moderate flow tissues using 62,64Cu-PTSM, PET imaging and continuous arterial sampling with n-octanol extraction.