We studied the decay of 189W as produced via the 192Os[n,alpha]189W reaction on a 99.9% isotopically enriched 192Os target. The irradiations were performed at the intense neutron beam facility at Cyclotron Research Center, Université Catholique Louvain-la-Neuve (CRC-UCL) (Belgium), where fast neutrons [En approximately 20 MeV, phi(n) = (4.8 +/- 0.3)10(11) ns(-1) cm(-2)] were generated by stopping 50 MeV deuterons on a thick Be target. The half-life of 189W was determined to be 9.3 +/- 0.3min, compared to 10.8 +/- 0.2min obtained from the 188W[n,gamma]189W reaction. The energies of the two predominant gamma-rays of 189W, 260.4 +/- 1.3 and 421.7 +/- 1.4 keV were in good agreement with that from the [n,gamma] reaction, however, the relative intensities of the two gamma-rays were not consistent. From the [n,gamma] reaction, the relative intensities of the 260 and 421 keV gamma-rays were 97 to 100, whereas from the [n,alpha] reaction the relative intensities were 100 to 77, respectively. Assuming a cross-section ratio of 20 +/- 5 for [n,p3n] to [n,alpha] reactions, a cross-section of 0.5 +/- 0.2 mb was suggested for the 192Os[n,alpha]189W reaction, and the absolute intensity of the 260 keV gamma-ray was estimated to be approximately 50%.

Institute of Nuclear Technology, P-2686–953 Sacavem, Portugal and National Center for Scientific Research ‘Demokritos’, Athens, Greece

PET is potentially very useful for the accurate in vivo quantitation of time-varying biological distributions of radiolabeled antibodies over several days. The short half-lives of most commonly used positron-emitting nuclides make them unsuitable for this purpose. Iodine-124 is a positron emitter with a half-life of 4.2 days and appropriate chemical properties. It has not been widely used because of a complex decay scheme including several high energy gamma rays. However, measurements made under realistic conditions on several different PET scanners have shown that satisfactory imaging and quantitation can be achieved. Methods: Whole-body and head-optimized scanners with different detectors (discrete BGO, block BGO and BaF2 time-of-flight), different septa and different correction schemes were used. Measurements of resolution, quantitative linearity and the ability to quantitatively image spheres of different sizes and activities in different background activities were made using phantoms. Results: Compared with conventional PET nuclides, resolution and quantitation were only slightly degraded. Sphere detectability was also only slightly worse if imaging time was increased to compensate for the lower positron abundance. Conclusion: Quantitative imaging with I-124 appears to be possible under realistic conditions with various PET scanners.

Gel generators based on Zn, Co, Ni, Mn and Pb tungstates were prepared as potential supports for the development of Re-188 radiopharmaceuticals. Factors which affected either the elution efficiency of Re-188 or the breakthrough of W-188 were examined. Re-188 was produced as perrenate when the generators were eluted with saline (0.15M NaCl) and different organic solvents. The elution yield of Re-188 decreased for the various gel supports as: Zn (75%), Co (60%), Ni (37%), Mn (24%), Pb (15%). When a "tandem" system comprised of a chromatographic alumina column was utilized in combination with the gel generator the W-188 breakthrough was controlled to of the order of 10(-6)%.

Gel generators based on Zn, Co, Ni, Mn and Pb tungstates were prepared as potential supports for the development of188Re radiopharmaceuticals. Factors which affected either the elution efficiency of188Re or the breakthrough of188W were examined.188Re was produced as perrenate when the generators were eluted with saline (0.15M NaCl) and different organic solvents. The elution yield of188Re decreased for the various gel supports as: Zn (75%), Co (60%), Ni (37%), Mn (24%), Pb (15%). When a “tandem” system comprised of a chromatographic alumina column was utilized in combination with the gel generator the188W breakthrough was controlled to of the order of 10−6%.

An improved188W-188Re gel generator based on Zr tungstate is described. The influence of synthesis parameters and pre-treatment conditions on188Re elution yields and the188W breakthrough was studied with 0.15M aqueous solution of NaCl at pH 5.3 to 7.3 as well as with some organic solvents. An elution efficiency of 80% was achieved during 3 month of explotation with 0.15M NaCl at pH=6.3. The188W breakthrough was 10−4 to 10−3%. The188W breakthrough may be decreased to 10−6% when converted into tandem generator with an alumina column. However,188Re yields are reduced by 8–12% with a tandem generator.

Liver metastases cause the majority of deaths from colorectal cancer and response to chemotherapy is poor. Intrahepatic arterial 90Y-microspheres may induce tumour regression but the β-radiation dose is variable and cannot be determined in patients. The 81 keV γ emission of holmium-166 (166Ho) was used to determine, by single photon emission computed tomographic (SPECT) imaging, the β-radiation absorbed dose to normal liver in pigs following intrahepatic arterial administration of 166Ho-microspheres. The SPECT system was calibrated with anthropomorphic liver phantoms containing known activity concentrations of 166Ho-chloride. The relationship of SPECT counts to phantom activity concentration was linear with a correlation coefficient of r = 0.996. The SPECT pattern of liver distribution following successive administrations of tracer activities of 166Ho-microspheres was similar. The ratio of initial to total SPECT estimates of mean activity concentration in regions of interest, from which anatomically matched biopsy samples were later obtained and counted in an ionization chamber, showed good correlation (r = 0.924). Prospective SPECT dosimetry performed on a tracer activity of 166Ho-microspheres predicted the total administered activity required to deliver a prescribed radiation absorbed dose of 25 Gy to the liver within an error of ± 8%. This study demonstrates the feasibility of prospective control of the absorbed radiation dose to the critical normal organ by SPECT dosimetry on a tracer dose of 166Ho-microspheres prior to administration of a therapy dose.

Liver metastases cause the majority of deaths from colorectal cancer and response to chemotherapy is poor. Intrahepatic arterial Y-90-microspheres may induce tumour regression but the beta-radiation dose is variable and cannot be determined in patients. The 81 keV gamma emission of holmium-166 (Ho-166) was used to determine, by single photon emission computed tomographic (SPECT) imaging, the beta-radiation absorbed dose to normal liver in pigs following intrahepatic arterial administration of Ho-166-microspheres. The SPECT system was calibrated with anthropomorphic liver phantoms containing known activity concentrations of Ho-166-chloride. The relationship of SPECT counts to phantom activity concentration was linear with a correlation coefficient of r = 0.996. The SPECT pattern of liver distribution following successive administrations of tracer activities of Ho-166-microspheres was similar. The ratio of initial to total SPECT estimates of mean activity concentration in regions of interest, from which anatomically matched biopsy samples were later obtained and counted in an ionization chamber, showed good correlation (r = 0.924). Prospective SPECT dosimetry performed on a tracer activity of Ho-166-microspheres predicted the total administered activity required to deliver a prescribed radiation absorbed dose of 25 Gy to the liver within an error of +/- 8%. This study demonstrates the feasibility of prospective control of the absorbed radiation dose to the critical normal organ by SPECT dosimetry on a tracer dose of Ho-166-microspheres prior to administration of a therapy dose.

The advantages of radiation synovectomy, using preparations containing dysprosium-165 (Dy-165), over conventional materials based on yttrium-90 (Y-90) include a more ideal spectrum of decay energies, and a much shorter half-life permitting quicker and more efficient treatment. A new therapeutic agent, Dy-165 hydroxide macroaggregates, has been developed for the treatment of arthritis making use of these advantages. As part of a clinical trial of this material 42 patients were examined for micronucleus frequency in their peripheral blood lymphocytes prior to, and 2 weeks after, radiation synovectomy using Dy-165 hydroxide macroaggregates or Y-90 silicate. In the majority of patients from each treatment group no significant increase in micronucleus frequency was observed. This indicates that in these cases leakage of material from the site of treatment was not resulting in detectable irradiation of circulating cells irrespective of the choice of radiopharmaceutical. The maximum increase in micronucleus frequency observed corresponded to a radiation dose to circulating cells of approximately 0.3 Gray.

PET has inherently high resolution and excellent contrast imaging and accurately measures radioactivity concentrations in vivo. When combined with specific immunological targeting it might provide a highly specific and sensitive radioimmunoscintigraphic tool. To investigate this we injected 124 I-labeled MAb MX35 or MAb MH99 monoclonal antibodies (doses 200-400 μCi) intravenously into nude rats bearing subcutaneous human ovarian cancer xenografts (SK-OV-7 and SK-OV-3 cell lines). A melanoma cell line (SK-MEL-30) was used as a control tumor. These murine monoclonal antibodies react with cell-surface antigens expressed by most ovarian cancer cells, including the ovarian cell lines used. Imaging was performed at 1-6 days using a high-resolution positron emission tomograph (PCR-I) with a spatial resolution of 4.5 mm. The slice thicknesses were 0.5 and 1.0 cm. Forty to seventy thousand coincident pulses were obtained per frame. The PET results were compared with those of autopsy and histology. Samples of blood, tumor, and normal tissues were obtained at various time points. PET calculation of isotope uptake ratios demonstrated specific localization of the antibodies in tumor, with ratios of tumor to normal tissue uptake as high as 6:1. Subcutaneous ovarian cancer nodules as small as 7 mm were identified with PET imaging. The results corresponded well with tissue sampling. Our findings suggest that PET imaging of tumors with 124I-labeled monoclonal antibodies may be useful in human diagnostic and therapeutic applications in ovarian cancer as well as other diseases.

A patient with advanced neuroblastoma who had failed chemotherapy presented with a large abdominal mass and virtually total bone marrow replacement by tumor on repeated marrow biopsies. She was considered a candidate for a Phase I 131I-3F8 radioimmunotherapy trial, (MSKCC 89-141A). As a potential aid to treatment planning, a test dose of 124I-3F8 was injected and the patient was imaged over the 72 hr postinjection using two BGO based PET scanners of different designs. Time activity curves were obtained, and the cumulated activity concentration of radiolabeled 3F8 in tumor was determined. Based on MIRD, an estimated radiation absorbed dose for 131I-3F8 was 7.55 rad/mCi, in the most antibody avid lesions. Because of low uptake and unfavorable dosimetry in some bulky tumor sites, it was decided not to treat the patient with radiolabeled antibody. Positron emission tomography of 124I-labeled antibodies can be used to measure cumulated activity or residence time in tumor for more accurate estimates of radiation absorbed tumor dose from radioiodinated antibodies and can help guide management decisions in patients who are candidates for radioimmunotherapy.

Positron emission tomography (PET) is potentially useful for the quantitative imaging of radiolabeled antibodies, leading in turn to improved dosimetry in radioimmunotherapy. Iodine-124 is a positron-emitting nuclide with appropriate chemical properties and half-life (4.2 days) for such studies since the radiolabeling of antibodies with iodine is well understood and the half-life permits measurements over several days. Unfortunately, I-124 has a complex decay scheme with many high-energy gamma rays and a positron abundance of only 25%. It has therefore been largely ignored as a PET-imaging nuclide. However, measurements made with phantoms and animals under realistic conditions using a BGO-based PET scanner have shown that satisfactory imaging and quantitation can be achieved. Investigations of spatial resolution, the linearity of regional observed count rate versus activity in the presence of other activity, and the visualization and quantitation of activity in spheres with different surrounding background activities were carried out with phantoms up to 22 cm in diameter. Compared with F-18, spatial resolution was only slightly degraded (13.5 mm FWHM vs 12 mm FWHM) while linearity was the same over a 10:1 activity range (0.015 to 0.15 MBq/ml for I-124). The visualization and quantitation of spheres was also slightly degraded when using similar imaging times. Increasing the imaging time for I-124 reduced the difference. To verify that the technique would work in vivo, measurements were made of human neuroblastoma tumors in rats which had been injected with I-124 labeled 3F8 antibody. Although the number of samples was small, good agreement was achieved between image-based measurements and direct measurements of excised 4-g tumors. Thus quantitative imaging of I-124 labeled antibodies appears to be possible under realistic conditions.

The radiochemical synthesis of 2−[11C]cyano-isonicotinic acid hydrazide was accomplished. Carbon-11 labelled cyano-group was introduced at the 2-position of the pyridine ring of 1-methoxy-4-methoxycarbonyl pyridinium methyl sulfate via a Reissert-Kaufmann type reaction. The reaction was performed on a solid support (silica gel) to yield no-carrier-added methyl 2−[11C]cyano-isonicotinate in (32.4 ± 12%) (EOB) yield. This method is unique for the incorporation of [11C]HCN to base sensitive substrates. The carbon-11 labelled methyl ester was treated with hydrazine hydrate to obtain 2−[11C]cyano-isonicotinic acid hydrazide. The final radiochemical yield was 10% (EOB) and the synthesis time was approximately 35 min.

The radiochemical syntheses of methyl 2-[123I]-iodoisonicotinate, 2-[123I]-iodoisonicotinic acid hydrazide and 2-[124I]-iodoisonicotinic acid hydrazide was accomplished. Iodine-123 was incorporated in the methyl ester molecule by an exchange reaction in glacial acetic acid. The average efficiency of iodine exchange reaction was (92.6 ± 4.5)%. This radiotracer was extracted with ether and the solvent was evaporated. The residue was re-dissolved in anhydrous ethanol and treated with hydrazine under anhydrous conditions to obtain 2-[123I]-iodoisonicotinic acid hydrazide. The overall radiochemical yield was 69%. Biodistribution data of both radio-tracers in male Sprague-Dawley rats were collected. This is the first report of SPECT radiopharmaceuticals which may be useful for differential diagnosis of intracranial masses (tuberculoma vs glioma), and CNS tuberculosis in immunosuppressed subjects.

A convenient technique is described for removal of sodium and other metal ion interference from sodium iodide-123 and sodium iodide-124 solutions used to label antibodies. Distillation methods have disadvantages compared to column purification techniques used to remove salt impurities that interfere in radioiodination reactions.

L'agence internationale sur l'energie atomique a organise une reunion consultative pour definir les criteres de base du controle de qualite des radiomedicaments produits par cyclotron et pour etablir les principes de leur manipulation. Ce controle de qualite est rendu necessaire pour assurer l'efficacite et l'inocuite des preparations juste avant leur administration

The radiopharmaceutical 6β-[124I]iodomethyl-19-norcholest-5(10)-en-3β-ol (NCL-6-124I) was synthesized. The product was less sensitive to autoradiolytic decomposition in chloroform, than when stored as an injectable solution at 5°C.

A silica gel solid-state support was used to trap [11C]-HCN for the synthesis of 11C-labelled compounds including base sensitive compounds; examples of the Reissert–Kaufmann type reaction and Michael addition are given.