Journal of nuclear biology and medicine (Turin, Italy: 1991) (J Nucl Biol Med )

Publisher: Società italiana di biologia e medicina nucleare


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    Journal of nuclear biology and medicine
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    Journal / Magazine / Newspaper

Publications in this journal

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    ABSTRACT: Radiolabelled amino acids combined with Positron Emission Tomography (PET) may be useful for delineation of the extent of viable tumour and may also provide a rapid and sensitive indicator of response to therapy. Promising early clinical reports led us to investigate the potential use of the amino acid analogue L-3-iodo-alpha-methyl tyrosine (IMT), which may be radioiodinated with isotopes suitable for PET or conventional single photon imaging. We have studied the biodistribution and kinetics of [125I]IMT using two transplantable tumour systems in hooded rats, and have compared the findings with those using the natural amino acid L-tyrosine (TYR) radiolabelled with tritium. Similar levels of IMT and TYR uptake were found in HSN and OES.HR1 tumours during tumour growth. Following arrest of OES.HR1 tumour growth by oestrogen ablation, reduced IMT and TYR uptake was found to be closely matched by a fall in tumour blood flow. Unlike IMT, a substantial proportion of TYR uptake in tumours was found to be protein incorporated, even following tumour growth arrest. Quantitative autoradiography revealed sharp delineation of tumour boundary using either radiotracer. We conclude that IMT and TYR kinetics are strongly influenced by blood flow and diffusion, and that tumour growth status may not be closely associated with amino acid uptake.
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):92-5.
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    ABSTRACT: In order to assess the practical reliability of glomerular filtration rate (GFR) determination with 99mTc-DTPA and plasma sampling, the authors compared the results obtained with 51Cr-EDTA and 99mTc-DTPA in 50 patients using five easily applied methods (two double-plasma-sample methods and three single-plasma-sample methods), and two kits with different compositions. It was observed that: 1) there is no difference between the results obtained with the two different kits. 2) Compared with 51Cr-EDTA the 99mTc-DTPA overestimates the result by about 2 mL/min: precision is slightly lower with 99mTc-DTPA than with 51Cr-EDTA but is sufficient for practical use. 3) The method recommended by the authors on the basis of this experience is the Russell's method with two samples. 4) The simplified methods with one sample give comparable results to the Russell's method for GFR levels between 50 and 115 mL/min, while the results are unsatisfactory below 50 mL/min. 5) Among the single-sample methods, the authors suggest that of Christensen and Groth. 6) A preliminary estimate of GFR (from the serum creatinine level, for instance) is useful for the choice between double-plasma-sample methods and simplified methods. In conclusion, the authors consider that the estimation of GFR with 99mTc-DTPA can be performed efficiently in clinical practice even when operating in absolutely routine conditions.
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4):556-65.
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    ABSTRACT: 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)
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):135-9.
  • Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):22-32.
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    ABSTRACT: Dynamic cardiomyoplasty improves ventricular function by increasing pump function and by limiting cardiac dilatation. The aim of this study was to assess long-term myocardial performance by radionuclide ventriculography on dilated cardiomyopathy patients subjected to cardiomyoplasty. Thirteen survivors were included. Radionuclide ventriculography was performed one week before surgery and one year later. Five patients were also studied two years following surgery. The left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and ventricular amplitude ratio (VAR) to assess mitral regurgitation were measured. Every case after one year showed a non-significant increase in LVEF. However, the decrease in EDV and in VAR was significant (p < 0.01). No significant difference in these values was found after two years. We conclude that the effects of cardiomyoplasty--reduction of cardiac dilatation, wall stress and mitral regurgitation--are more evident during the first year after surgery. Thereafter, a certain stabilization is observed.
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4):535-9.
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    ABSTRACT: Thirty-five patients with painful bone metastases arising from a variety of tumor types underwent a clinical trial in which 153Sm-EDTMP was injected as a single intravenous dose. The injection ranged in amount from 330 MBq to 1110 MBq of 153Sm-EDTMP. Pain relief usually occurred within one week after administration. The duration of pain relief lasted from 2 to 17 weeks. A detectable degree of pain palliation was experienced by 80% of the treated patients; 54% reported substantial or complete pain relief. Due to the small number of patients, no clear-cut dose-related response was detectable. Moderate myelosuppression was observed in one patient (WHO grade III). The metastatic lesion-to-normal bone ratios remained constant (varying from 1.5 to 4.8) for at least 5 days post-injection. 153Sm cleared very rapidly from the blood. Less than 1% of the injected dose remained in circulation at 4 hours post-injection. No local accumulation of the tracer could be detected outside the skeleton. Urinary excretion was quite complete at 6 hours post-injection. The biodistributions of 153Sm-EDTMP and 99mTc-DPD are very similar in metastatic and normal bone; thus, bone scanning can be used for patient selection and followup. According to our results, it seems that higher doses of 153Sm-EDTMP can be given safely and without any irreversible myelosuppression.
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):123-7.
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    ABSTRACT: A stable 99mTc-labelled compound that is easy to prepare and that is retained for a long period of time in the blood would constitute an ideal replacement for 99mTc-HSA (limited by its rapid diffusion) and 99mTc-erythrocytes (lengthy and risky in vitro labelling) as tracer agent for ventriculography. We investigated whether 99mTc-labelled polymers would be suitable for this purpose. Four types of poly-L-lysine (PL) (Mw 41,000 to 377,000) were used either in underivatized form labelled at pH 12, or derivatized with a varying number of mercaptoacetyl (MA) substituents by reaction with N-hydroxysuccinimidyl-S-acetylmercaptoacetate followed by deprotection with hydroxylamine and labelling at pH 7.5. A high labelling yield was obtained in all cases. HPLC-purified 99mTc-PLs and 99mTc-MA-PLs were evaluated in mice, with 125I-HSA as an internal biological standard. The retention in the blood at 10 minutes and 60 minutes p.i. was not higher than about 30% for any of the tested compounds versus 84% for 125I-HSA, and was only 10% for the smallest 99mTc-labelled PL and MA-PL. Liver uptake was high for the 99mTc-PLs, whereas the 99mTc-MA-PL's were excreted in significant amounts to the urine. It is concluded that 99mTc-labelled poly-L-lysines or polymercaptoacetyl-poly-L-lysines are not suitable as blood pool tracer agents.
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):75-8.
  • Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):3-14.
  • Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4):573-5.
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    ABSTRACT: With a view to evaluating the role of PET imaging in early clinical studies of new anticancer drugs, we are investigating the recently developed antiestrogen compound pyrrolidino-4-iodo-tamoxifen (idoxifene). Preliminary experimental studies have been undertaken using [125,131I]idoxifene, following synthesis of a tributyl-stannyl-idoxifene precursor to facilitate radioiodination. We have investigated the tissue biodistribution and kinetics of [125I]idoxifene following i.v. infusion in hooded rats bearing the hormone-dependent transplantable mammary tumour OES.HR1. Clearance of idoxifene from the circulation is accompanied by an increase in uptake by tumour and uterus, to peak levels after 24 hours (0.33 +/- 0.037% dose/g (mean +/- 1 SD) and 0.40 +/- 0.033% dose/g, respectively). Highest uptake of idoxifene was found in the liver (11.0 +/- 0.8% dose/g), with a progressive fall after 24 hours consistent with hepatobiliary excretion of the radiotracer. No evidence of idoxifene metabolism was found in tissue extracts taken up to 48 hours. Whole body clearance of [131I]idoxifene was characterised by a single exponential decay (t1/2 = 140 hours) up to 350 hours post administration. We conclude that 124I-labelled idoxifene combined with PET imaging would facilitate human in vivo pharmacokinetic studies of this new anticancer drug and provide an opportunity to investigate relationships between drug uptake and tumour response.
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):96-8.
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    ABSTRACT: 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.
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4):579-85.
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    ABSTRACT: In 28 blood samples from 21 patients undergoing 131I treatment after surgical thyroidectomy for cancer, the micronucleus (MN) frequency observed in peripheral blood lymphocytes (MN-test on binucleated cells) had a weighted mean of 0.044 +/- 0.006 (SEM), which was significantly different (p < 0.001) from that observed in 93 healthy individuals (0.025 +/- 0.001). The MN frequency (F(MN)) of the patients correlated fairly well (R = 0.736) with the modified activity (Amod) calculated by the following equation: [formula: see text] where Ai is the 131I activity on a determined day, e the logarithm base, di the number of days that have passed between the determined day and the day when the blood was drawn, and k is a day coefficient, defined in this context as the "daily attenuation factor". The use of the value of 0.0003 for k allowed the following equation to be obtained: F(MN) = 7.9 x 10(-5) (+/- 1.4 x 10(-5)).Amod + 0.014 (R = 0.736) The MN frequency was used to estimate, by our DOSIME program, the dose (Gy) received at the individual level in the 131I treatment. In these subjects the calculated dose was well correlated with Amod by the relationship: DBio = 0.0009 (+/- 0.0002).Amod + 0.0675 (R = 0.755) 3-aminobenzamide (3AB), an inhibitor of the poly(ADP-ribose)polymerase enzyme involved in DNA repair, induced and increase in X-ray cytogenetic damage (MN yields), evaluated at the individual level using the 3AB-index (I-3AB). The index was obtained from the MN-yield count after x-irradiation with (MN + 3AB) and without (MN - 3AB) 3AB, using the following formula: I = 1-(MN - 3AB/MN + 3AB).(ABSTRACT TRUNCATED AT 250 WORDS)
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4):586-93.
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    ABSTRACT: Oxamniquine (OXY), a tetrahydroquinoline derivative, is used as an antischistosomal drug and generally has been labeled with carbon-14 and tritium. We decided instead to label it with technetium-99 (99mTc). In order to determine the optimal conditions, different concentrations of this drug were incubated with various stannous chloride solutions. We then added 99mTc, and chromatography was performed using 0.9% NaCl solution, acetone and 1.2N HCl as the mobile phase. Using a solution of 1.0 mg/mL stannous chloride and 0.5 mg/mL oxamniquine, over 94% of the radioactivity bound to oxamniquine (99mTc-OXY). In the biodistribution study, 99mTc-OXY was administered in mice intramuscularly, orally and intravenously. When the intramuscular route was used, the main uptake (after 30 minutes) of the labeled drug was in the kidneys, liver and intestines; after 240 minutes the labeled drug was still found in the liver and kidneys, but at increased levels in the intestines. It was also present in the faeces. When the oral route was employed, labeled OXY was mainly found in the stomach after 30 minutes, but there was a decrease after 240 minutes. During this period radioactivity increased in the intestines. When the intravenous route was employed the labeled OXY was found in the liver and spleen. The radioactivity decreased with time in these organs. Using infected animals, radioactivity was found in isolated worms.
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):109-12.
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    ABSTRACT: 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.
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):43-53.
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    ABSTRACT: A case of a patient with small cell lung cancer and right submandibular node enlargement due to granulomatous lymphadenitis is presented. Diagnostic procedures included: biopsy of the cervical node, transmission computed tomography of the chest, bronchoscopic examination and biopsy of the pulmonary lesion. The patient underwent 111In-octreotide scintigraphy (whole body and single photon emission tomography) which revealed both lesions. We conclude that granulomatous lesions are to be considered as a possible cause of false positive results, when octreotide scintigraphy is used to evaluate distant metastases in patients with known cancer.
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4):576-8.
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    ABSTRACT: Cysteinyltriglycine (CYSG3) is a derivative of MAG3 in which the mercaptoacetyl group is replaced by a cysteinyl moiety. This implies the presence of a primary amino group on the ligand, as in case of p-amino-hippuric acid, the compound with the highest renal tubular secretion known. The present study was undertaken to investigate the influence of this amino group on the biological behaviour of complexes of 99mTc with MAG3-like molecules. The L- and D-isomers of cysteinyltriglycine were synthesized as S-benzyl N1-CBO protected precursors. After removal of the protective groups with Na/NH3, the isomers were labelled with 99mTc. This resulted in the formation of two diastereomeric complexes (A and B in the order of HPLC-elution) for each of them. The biodistribution of the four HPLC-purified isomers was tested in mice. Isomers DA and LB showed slightly superior or similar renal excretion characteristics compared to 99mTc-MAG3, whereas the two other isomers were cleared at a lower rate by the kidneys and more through the liver and the intestines. The results indicate that substitution of 99mTc-MAG3 with an amino function may somewhat improve the rate of renal excretion, but the configuration of the 99mTc-labelled complexes appears to be more important to its biological behaviour.
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):69-74.
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    ABSTRACT: The monoclonal antibody (MoAb) 174H.64 (Truscint SQ, Biomira Inc.) is a murine-derived MoAb reacting with an extracellular surface component of the cytoskeletal matrix ectopically expressed on squamous-cell carcinoma cell-surface membranes. A chimeric form of this MoAb has also been produced by genetically modifying the Fc portion of the MoAb by the insertion of a human Fc fragment. During this process the isotype was altered from an IgG1 (murine) to an IgG3 (chimeric). Pilot and phase I/II clinical trials of the murine and chimeric 99mTc-labelled 174H.64 MoAbs have been undertaken at selected European and North American sites. As part of this evaluation serum, urine and image data were collected at specific time intervals and used to obtain a kinetic model to describe the in vivo distribution of the MoAbs. A two-compartment model of the form: C(t) = C1 e-lambda 1t + Cz e-lambda zt was found to best describe the serum distribution of radioactivity of both the murine and chimeric MoAbs. The initial distribution half-lives were 2.9 +/- 0.7 hours and 2.7 +/- 0.2 hours, and the terminal elimination half-lives were 17.6 +/- 3.8 hours and 22.5 +/- 1.3 hours for the murine and chimeric MoAbs, respectively. No significant difference was found between the kinetic model parameters of two MoAbs at the 95% level. Assuming a similar clinical efficacy, these MoAbs could then be used interchangeably, with the chimeric MoAb offering potential advantages in reducing HAMA response.
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):140-4.
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    ABSTRACT: 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.
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):54-8.
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    ABSTRACT: There are various approaches for improving endoradiotherapy and diagnosis with monoclonal antibodies in nuclear medicine. The known methods of site-specific labelling of biomolecules based either on reactions with sulfhydryl groups or on reactions with aldehyde groups of the oligosaccharide chains effect unwanted alterations of the biomolecules. We present a new method to introduce radioactive halogens into the oligosaccharide chains of an antibody, based on the enzymatic transfer of the labelled synthetic sialic acid derivative CMP-9-deoxy-9-salizoyl-NeuAc. It was first labelled by the iodogen-method (iodine) in yields of more than 90%. Under selected conditions it was possible to obtain di- and trihalogenated products. Then the radioactive sialic acid derivatives were transferred during 90 minutes at room temperature with 2.6-sialyltransferase from rat liver into the oligosaccharide chains of antibodies. It is necessary to use neuraminidase pretreated antibodies with an increased number of binding sites for sialic acid derivatives. Yields of about 55% were obtained for the monoiodinated sialic acid derivative. With this method we present a reasonable alternative reaction of labelled compounds with biomolecules. Studies of the immunoreactivity are now in progress.
    Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):15-7.
  • Journal of nuclear biology and medicine (Turin, Italy: 1991) 01/1995; 38(4 Suppl 1):119-22.

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