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

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.

We examined the role of various medical imaging modalities, particularly metaiodobenzylguanidine (MIBG) scintigraphy in the investigation of patients presenting with the opsoclonus-myoclonus syndrome (OMS) who may harbor neuroblastomas. A retrospective analysis was therefore performed of all patients presenting with OMS in a 5 1/2 year period. Between December, 1988 and May, 1994, all 13 patients (mean age 15.2 months, range 3 days-30 months) presenting with OMS were extensively studied. A wide range of medical imaging modalities including CT, MRI and [131I] or [123I]-metaiodobenzylguanidine (MIBG) scintigraphy (total of 21 scans) were examined as a means of detecting a structural brain lesion or locating a neuroblastoma, a tumor generally found in less than half of patients with OMS. As anticipated a minority of patients (4) were eventually found to harbor neuroblastomas. In these four cases, two tumors were revealed on preoperative MIBG scintigraphy, one gave a false negative study and one tumor was not studied preoperatively. Each patient was also subjected to extensive radiological investigations in addition to MIBG scintigraphy, many of which were repetitive, redundant or had low clinical yield. The relative merits of the various procedures are compared, and an algorithm incorporating MIBG scintigraphy and limited central nervous system and abdominal anatomical modalities for the investigation of opsoclonus-myoclonus is suggested.

Two anti-CEA antibodies, B2C114 and IORCEA1, were radiolabeled with 99mTc by two direct methods (mercaptoethanol and ascorbic acid reduction), and the radio-immunoimaging properties of B2C114 were assessed in mice bearing an M3-reactive tumor. The labeling efficiency was greater than 90% as measured by ITLC in saline, methylethylketone and with serum albumin impregnated sheets using ethanol: water: NH4OH (2:5:1). The label was stable to challenge with excess DTPA, and in the case of ascorbic acid reduction, serum analysis showed that 10-15% of the radioactivity was lost during incubation. In vitro studies demonstrated that the radiolabeled antibodies retained their immunoreactivity. Biodistribution studies in normal Balb/c mice showed that the pattern of uptake was quite similar for both antibodies. Biodistribution of the 99mTc-B2C114 and image studies in the animal model showed that the tumor was clearly visualized and that B2C114 labeled with 99mTc is a possible candidate for human radioimmunodetection of CEA-expressing tumors.

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.

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.

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.

The established clinical role of radionuclide imaging includes the diagnosis and monitoring of a wide range of clinical conditions. The therapeutic use of radionuclides has centred on a relatively small number of pathological conditions, particularly within the field of oncology. More recently there has been growing interest in the use of radionuclide imaging in drug evaluation and research (RIDER). Studies have been undertaken in order to increase the understanding of the in in vivo behaviour of pharmaceutical dosage forms in addition to the in vivo behaviour of molecular and cellular anti-tumour agents. The imaging facilities required for such undertakings are available in most nuclear medicine departments, although the expertise for radiolabelling and the requirements for the production of drug conjugates and pharmaceutical formulations are limited to a small number of centres. This paper discusses the application of radionuclide imaging in drug research with particular reference to the role of gamma-scintigraphy in monitoring the biodistribution and pharmacokinetics of immune mediated drug conjugates intended for the treatment of malignant disease. Examples described include the evaluation of oral and inhaled drug delivery systems and the biodistribution and in vivo kinetics of parenteral administrations.

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.

Iridium-191m (191mIr, t1/2 = 4.96 sec), an ultra-short lived tracer, has turned out to be suitable for gamma imaging. It can be obtained in high yields from an 191Os/191mIr-generator with a low 191Os breakthrough. In this study the blood flow in the carotid and kidney arteries was studied in rabbits by radionuclide arteriograms. In addition, the whole body retention and biodistribution of 191Os was studied in rats. 191mIr was obtained from an activated carbon system, in a modification of the procedure described in the literature. The kidney regions (study I) of rabbits were imaged dynamically (5 frames/second) for up to 40 seconds, and the investigations were repeated 4-7 times in the same animal. Similarly, the carotid arteries were studied (study II) and from the curves flow parameters were calculated. In order to study the 191Os breakthrough two groups of rats (n = 5) were sacrificed one day and four days after injecting five diagnostic doses into the tail vein (study III). In study III the Os-retention was highest in the kidneys and spleen, followed by the muscles and liver: 0.11-0.12% ID/g tissues were obtained at 1 day and 0.10-0.13% ID/g at 4 days, respectively. These values indicate that the breakthrough values are by no means toxic and that investigations can be repeated immediately with a negligible radiation exposure. The investigations performed with the same animals (I-II) could be easily repeated and were reproducible. All of this indicates that 191mIr is suitable for radionuclide angiography and the generator system is simple and safe to use (191Os is beta-emitter).(ABSTRACT TRUNCATED AT 250 WORDS)

beta-CIT (2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane) is a new ligand that has a high affinity to dopamine and serotonin re-uptake sites. [123I] beta-CIT was prepared by reacting the corresponding trimethylstannyl precursor with no-carrier-added 123I. Iodogen was used as an oxidizing agent. The labeling mixture was purified by filtration through a mini-column. The purity of the product was confirmed by analytical HPLC. The total radiochemical yield was 67 +/- 5%. The radiochemical purity was > 95% and the specific activity was > 107 GBq/mol (> 2900 Ci/mmol). The final product was confirmed to be free of endotoxins before intravenous administration. Two healthy male volunteers were injected iv with 120-160 MBq of [123I] beta-CIT and scanned with a 3-head gamma-camera (Siemens MultiSPECT3). Dynamic SPECT scans were performed for up to 2 hours. There was a high accumulation of radioactivity in the striatum and in the thalamus, and some in the medial prefrontal area. Thus, we have developed an easy method to prepare [123I] beta-CIT with a high specific radioactivity and in a sufficient radiochemical yield. Specific [123I] beta-CIT binding in striatal and thalamic regions was demonstrated in humans. [123I] beta-CIT is a potential marker of the dopamine and serotonin transporters and can be used to study the pathophysiology of Parkinson's disease, as well as neuropsychiatric disorders.