Bernard Bok

Reversibility of thyroid dysfunction induced by recombinant alpha interferon in chronic hepatitis C.

OBJECTIVE Thyroid dysfunction has been reported as a complication of interferon therapy. The aim of our study was to assess the risk factors and reversibility of thyroid disorders induced by interferon therapy.

Sustained hypothyroidism induced by recombinant alpha interferon in patients with chronic hepatitis C.

Thyroid dysfunction has been reported in patients with malignant disease treated with recombinant alpha interferon. Two cases of hypothyroidism in patients with chronic hepatitis C treated with recombinant alpha interferon are reported. In one patient, interferon induced hypothyroidism in the absence of pre-existing thyroid dysfunction and in the other it aggravated a pre-existing thyroid dysfunction. Both patients developed a severe, sustained hypothyroidism requiring thyroxine treatment for one year or more after stopping alpha interferon. Diagnosis of hypothyroidism during treatment can be difficult because of the common side effects of alpha interferon. Thyroid function should be assessed before and during alpha interferon therapy in patients with chronic hepatitis C.

Incidence of Dysthyroidism during Interferon Therapy in Chronic Hepatitis C

Seventy-nine patients (40 males, 39 females) were enrolled in a prospective study of lymphoblastoid interferon-alpha (IFN), 3-5 MU three times weekly. They were randomly assigned to receive either 12 months of IFN therapy, or to 6 months of observation followed by 6 months of IFN therapy. The thyroid functional and immunological status was checked every other month during and after treatment. Before treatment, antithyroid antibodies were found in 6 patients (7.5%). Two were hypothyroid and were excluded from the study before starting IFN therapy. Seventy-seven patients received IFN therapy. Of these, thyroid abnormalities appeared in 6 (7.5%). Hyperthyroidism was observed in 3 patients. Two recovered within a few months, but 1 developed subsequent hypothyroidism. Hypothyroidism was observed in 2 patients. TSH blood values were persistently abnormal, but thyroid antibody levels remained increased and fluctuating. Thyroid function usually recovered within a few months; but 2 patients required hormonal therapy and 1 was treated with carbimazole. In 1 patient, a small thyroid papillary carcinoma was observed, but no evidence of relationship with the liver disease or with IFN therapy was found. In a patient with chronic hepatitis C, systematic thyroid assessment should be performed before initiating IFN therapy, including clinical examination, and measurement of TSH and anti-thyroperoxidase antibodies (TPO Ab). During treatment, a TSH assay every other month appears to be necessary and sufficient.

Contribution of Single-Photon Emission Computed Tomography in the Diagnosis and Follow-Up of CNS Toxicity of a Cytarabine-Containing Regimen in Pediatric Leukemia

PURPOSE Cytarabine (ara-C) is one of the most effective chemotherapeutic agents in patients with acute leukemia (AL), with a clear dose effect. Use of high-dose ara-C is hampered, however, by a noticeable toxicity, particularly to the CNS. We investigated the usefulness of CNS perfusion imaging with technetium-99m ((99m)Tc)-hexamethyl-propylene-amine oxime (HMPAO) single-photon emission computed tomography (SPECT) concurrent to magnetic resonance imaging (MRI) to specifically assess the effects of standard- and high-dose ara-C in children with AL. PATIENTS AND METHODS Twenty-six perfusion studies using (99m)Tc-HMPAO SPECT were performed in 12 children (age range, 4 to 15 years) with AL after induction therapy, which consisted of a standard-dose ara-C, immediately after consolidation with high-dose ara-C, and later during follow-up (range, 6 to 44 months). The chemotherapy-related adverse events were monitored and correlated to SPECT and MRI. RESULTS After the induction phase, all children were neurologically normal on MRI. On SPECT imaging, four children displayed a slightly heterogeneous perfusion. After high-dose ara-C (4 to 36 g/m(2)), five children had regressive neurologic signs of potential toxic origin. Of these five children, only one had an abnormal MRI scan, whereas all patients showed evidence of diffuse cerebral and/or cerebellar heterogeneous perfusion on SPECT. The seven other patients without any neurologic symptoms had normal MRI scans; SPECT was normal for three patients and abnormal for four patients. On follow-up, for four children who had presented with clinical neurologic toxicity, SPECT improved in three patients and remained unchanged in one patients. In two of these four children, delayed abnormalities (T2 white matter hypersignal and cerebellar atrophy) appeared on MRI scans. CONCLUSION In our series, diffuse heterogeneous brain hypoperfusion is often the sole early objective imaging feature identified by SPECT of high-dose ara-C neurotoxicity, where MRI still demonstrates normal pictures.

Comparison of cellular and conventional dosimetry in assessing self-dose and cross-dose delivered to the cell nucleus by electron emissions of 99mTC, 123I, 111In, 67Ga and 201Tl

Abstract. The radionuclides used in nuclear medicine imaging emit numerous mono-energetic electrons responsible for dose heterogeneity at the cellular level. Sself, the self-dose per unit cumulated activity (which results from the radionuclide located in the target cell), and Scross, the cross-dose per unit cumulated activity (which comes from the surrounding cells) delivered to a target cell nucleus by electron emissions of technetium-99m, iodine-123, indium-111, gallium-67 and thallium-201 were computed at the cellular level. An unbounded close-packed hexagonal cell arrangement was assumed, with the same amount of radioactivity per cell. Various cell sizes and subcellular distributions of radioactivity (nucleus, cytoplasm and cell membrane) were simulated. The results were compared with those obtained using conventional dosimetry. Sself and Scross values depended closely on cell dimensions. While the self-dose depended on the tracer distribution, the latter affected the cross-dose by less than 5%. When the tracer was on the cell membrane, the self-dose was particularly low compared to the cross-dose, as the self-dose to cross-dose ratio was always less than 11%. In the case of cytoplasmic or cell membrane distribution of radioactivity, conventional electron dosimetry slightly overestimated the dose absorbed by the target cell nucleus (by 1.08- to 1.7-fold). In contrast, conventional dosimetry strongly underestimated the absorbed dose (1.1- to 75-fold) when the radioactivity was located in the nucleus. The discrepancies between conventional and cellular dosimetry call for calculations at the cellular level for a better understanding of the biological effects of radionuclides used in diagnostic imaging.

Non-medical exposure to radioiodines and thyroid cancer

Abstract. The Chernobyl accident, which occurred 32 years after the accidental exposure of Marshall islanders, resulted in the exposure of neighbouring populations to a mixture of iodine isotopes and in an increased incidence of thyroid cancer. The highest thyroid doses were received by the youngest age groups. This review describes the existing evidence, and examines factors that may have increased the risk. It also stresses problems with contemporary thyroid measurements, and the lack of information on the sensitivity of the thyroid to short-lived iodine isotopes and iodine-131. Practical considerations for nuclear physicians, epidemiologists and thyroidologists are discussed in the light of this major accident.

Auxiliary liver transplantation in patients with fulminant hepatic failure: Hepatobiliary scintigraphic follow-up

Auxiliary liver transplantation (ALT), retaining in place the liver of the recipient, has been proposed as an alternative to liver replacement in patients with fulminant hepatic failure (FHF). Hepatobiliary scintigraphy (HS) has proved a unique tool for the separate assessment of graft and native liver function. Forty-eight HS scans were performed, following the injection of technetium-99m trimethyl-bromo-imino-diacetic acid, in six patients who underwent ALT for FHF. Quantitative parameters were derived from the time-activity curves of both the graft and the native liver. The function of the graft remained normal as long as the patients remained under immunosuppressive therapy (IST). The function of the native liver was almost completely absent in the 1st month in five patients, but it improved gradually in four of them. IST was then decreased in four patients and finally withdrawn in three. Spontaneous graft atrophy occurred in two patients and the graft was removed in two. All of the patients in whom IST was reduced had a normal global hepatic function and selective uptake (RU) >30% at that time. In ALT patients with FHF, HS can distinguish non-invasively the functional performance of both the donor and the recipient liver and its evolution with time.

Cell Irradiation caused by diagnostic nuclear medicine procedures: dose heterogeneity and biological consequences

Abstract. Most radionuclides used for diagnostic imaging emit Auger electrons (technetium-99m, iodine-123, indium-111, gallium-67 and thallium-201). Their very short range in biological tissues may lead to dose heterogeneity at the cellular level with radiobiological consequences. This report describes the dosimetric models used to calculate the mean dose absorbed by the cell nucleus from Auger radionuclides. The techniques used to determine the biodistribution of radiopharmaceuticals at the subcellular level are also described and compared. Published examples of cellular dosimetry computations performed with radiotracers are reviewed in various clinical settings.Finally, the biological implications of the subcellular localization of Auger emitters are examined. While a number of efforts have been made to obtain dosimetric models and to estimate subcellular distribution of radioactivity, little is known of the cellular dosimetry of most radiopharmaceuticals used in diagnostic imaging. However, biological examples of selective radiotracer uptake have been shown, leading to extremely strong cell-cell dose heterogeneity. Furthermore, radiobiological experiments show that the biological effects of Auger emitters incorporated into DNA can be severe, with relative biological effectiveness greater than 1 compared with external X-rays. These findings clearly show that the assessment of biological risks associated with internal administration of diagnostic radiopharmaceuticals must focus not only on target organs as a whole, but also on the cellular level. This review proposes the most appropriate model for dosimetric computations (cellular or conventional) according to the subcellular distribution of radiotracers. The radionuclide of choice and the general strategy used to design new diagnostic radiopharmaceuticals are also discussed.

Proportional anatomical stereotactic atlas for visual interpretation of brain SPET perfusion images

A semi-automatic method was developed to determine the anterior (AC) and posterior (PC) commissures on brain single-photon emission tomographic (SPET) perfusion images, and then to draw the proportional anatomical Talairachs grid on each axial SPET image. First, the AC-PC line was defined on SPET images from the linear regression of four internal landmarks (frontal pole of the brain, inferior limit of the anterior corpus callosum, sub-thalamic point and occipital pole). Second, the SPET position of AC and PC points on the AC-PC line was automatically determined from measurements made on hard copies of magnetic resonance (MR) images of the patients. Finally, a proportional Talairachs grid was automatically drawn on each axial SPET image. To assess the accuracy of localization of AC and PC points, co-registered technetium-99m hexamethylpropylene amine oxime SPET and MR images from 11 subjects were used. The mean displacements between estimated points on SPET and true points on MRI (Δx=sagittal, Δy=frontal and Δz=axial displacement) were calculated. The mean displacements (in mm) were Δx=−1.4±1.8, Δy=−1.7±3.3 and Δz=−1.1±2.5 for AC, and Δx=−1.8±1.8, Δy=0.3±3.2 and Δ=−1.3±2.7 for PC. These displacements represented an error of less than 5 mm at the anterior or posterior pole of the brain or at the vertex. Intra- and inter-observer comparisons did not reveal significant differences in mean displacements. Thus, this semi-automatic method results in reproducible and accurate stereotactic localization of SPET perfusion abnormalities. This method can be used routinely for repeat follow-up studies in the same subject as well as in different individuals without requiring SPET MRI co-registration.

Advantage of fan beam collimators for contrast recovery of hyperfixation in clinical SPECT

The influence of the collimator on the contrast recovery of hyperfixation was studied using a dual-headed single photon emission computed tomography (SPECT) system with standard clinical acquisition parameters. Three parallel collimator sets and two fan beam collimator sets were tested with a Jaszczak phantom. The six spheres of the phantom were filled with /sup 99m/Tc, and four background levels were progressively obtained by adding radioactivity to the cylinder of the phantom, providing four hyperfixation levels. The effects of angular sampling and reconstruction filters have been tested. The statistical analysis was performed with analysis of variance (ANOVA). This study demonstrates the advantage of ultra-high resolution fan beam collimators for contrast recovery of hyperfixation with SPECT when using 64 projections over 360/spl deg/, in particular when the contrast is low. The authors also demonstrate that fan beam collimators permit smaller size hyperfixation detection.