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The protective effect of stable iodide against radiation on thyroid cells was investigated. One physiological effect of stable iodine is well-rooted: stable iodine leads to a reduced thyroid uptake of radioactive iodine. This work wants to focus on an intrinsic effect of stable iodine by which DNA-damage in cells is prevented. To investigate this intrinsic effect thyroid cells (FRTL-5) were externally irradiated by use of a linear accelerator (LINAC) applying energy doses of 0.01 Gy-400 Gy and by incubation with various activity concentrations of 131I (0.1-50 MBq/ml for 24 h). We added stable iodine (NaI) to the cells prior to external irradiation and investigated the effect of the concentration of stable iodine (1, 5, 15 µg/ml). In order to clarify whether thyroid cells have a distinctive and iodine-dependent reaction to ionizing radiation, keratinocytes (HaCaT) without NIS were exposed in the same way. As indicators for the cellular reaction, the extent of DNA fragmentation was determined (Roche, Mannheim, Germany). Both cell types showed distinct ability for apoptosis as proven with camptothecin. The addition of "cold" iodine from 1 to 15 µg/ml without irradiation ("negative control") did not change the response in both cell types. Plausibly, the radio-sensitivity of both cell types did increase markedly with increasing radiation dose but the radiation effect is diminished if iodine is added to the thyroid cells beforehand. The DNA-damage in thyroid cells after addition of cold iodine is reduced by a factor of 2-3. The skin cells did not show an significant change of radio-sensitivity depending on the presence of cold iodine. Elementary iodine possibly acts as a radical scavenger and thus markedly reduces the secondary radiation damage caused by the formation of cytotoxic radicals. This intrinsic radioprotective effect of iodine is seen only in cells with NIS.

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For planned and ongoing storage of liquid radioactive waste in a designated plant for a nuclear medicine therapy ward (decontamination system/decay system), detailed knowledge of basic parameters such as the amount of radioactivity and the necessary decay time in the plant is required. The design of the plant at the Department of Nuclear Medicine of the University of Cologne, built in 2001, was based on assumptions about the individual discharge of activity from patients, which we can now retrospectively validate. The decontamination factor of the plant is at present in the order of 10-9 for 131I. The annual discharges have been continuously reduced over the period of operation and are now in the region of a few kilobecquerels. This work emphasizes the high efficacy of the decontamination plant to reduce the amount of radioactivity released from the nuclear medicine ward into the environment to almost negligible levels.

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It is well known that a considerable amount of radioiodine is exhaled after radioiodine therapy (RIT) leading to unwanted radiation exposure through inhalation for non-involved persons. This study focuses on the amount of exhalation in the breath-out air of RIT-patients and the dosimetric consequences. Furthermore, the correlation between radioiodine uptake and exhalation was investigated. The radioiodine species were collected in a filter system and quantified over time by measurements with a scintillation counter. The dosimetric implications were then studied for different exposure scenarios. Of the activity administered to the patient, approximately 10-3% (50-110 ppm) is exhaled. The radioiodine inhalation taking place following exhalation in the vicinity yields doses of up to 500 µSv (children, staying with the patient immediately after application and for the next 8 h). Three days after administration the doses are significantly reduced. This study lays emphasis on previous assumptions that exhalation depends on thyroid storage. Regardless of the type of thyroid disease, the predominant form exhaled is organic radioiodine. The amount of exhaled radioiodine is small but from the point of view of radiation protection, by no means negligible immediately after administration. Radiation doses received by incorporation of exhaled radioiodine can easily exceed 100 µSv soon after administration of radioiodine. Three days after RIT the radioactivity can still be measured in the exhaled air but even at maximum, the annual doses lie far below 10 µSv and are thus comparatively low.

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Procedures to determine the release of hazardous gaseous substances including radioactive iodine are covered by different norms such as the European standard EN 14175 and the German national standard DIN 25466. The detection of sulphur hexafluoride (SF6) is required to comply with the prescribed methodology. The detection limit of this test is 4.5·10-7 mol/m3 in exhaust air. This detection limit would represent a very high activity in the region of 0.27 TBq/m3 leading to an unacceptable risk. We therefore developed a test using a filter system, consisting of a combination of filters capable of separating various chemical forms of airborne radioiodine. Air samples were collected directly in front of the fume hood and in the laboratory beside two different fume hoods of a similar construction with a final activated carbon filter for retention of radioiodine. Particular attention was therefore paid to air samples taken after passage over the filters. Significant differences in the degree of retention of iodine were found between the two fume hoods investigated. In one test a malfunction of the fume hood was demonstrated. In this case 0.148 × 10-3% of the total released activity per m3 air was found 1 cm in front of the hood sash. A remarkably high fraction of the activity released in the fume hood (1.3 × 10-3%/m3 air) was measured after the activated carbon filter. In the ambient air, values of up to 8.6 × 10-6% pro m3 laboratory air sampled were measured, despite a 6-8-fold air exchange. The selected procedure is a factor of 1011 (Schomäcker et al., 2001) more sensitive than the standard recommended methods (EN 14175). The standard test prescribed by the DIN/EN failed to reveal any inadequacy in the protective function of the radionuclide hood with respect to radioiodine retention.

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OBJECTIVES: Comparison of the binding affinity to a CD30-positive Hodgkin lymphoma (HL) cell line and biodistribution in HL bearing mice of new anti-CD30 radioimmunoconjugates (RICs) of varying structure and labelling nuclides. METHODS: The antibodies Ki-4 and 5F11 were radioiodinated by the chloramine T method or labelled with (111)In via p-NCS-Benzyl-DOTA. In addition, the Ki-4-dimer was investigated in the iodinated form. The RICs were analyzed for retained immunoreactivity by immunochromatography. In-vitro binding studies were performed on CD30-positive L540 cell lines. For in-vivo biodistribution studies, SCID mice bearing human HL xenografts were injected with the various radioimmunoconjugates. After 24 h, activities in the organs and tumour were measured for all 5 RICs. Tumour-free animals were studied in the same way with (131)I- Ki-4 24 h p. i. The three RICs with the highest tumour/background ratios 24 h p.i. ((131)I-Ki-4, (131)I-5F11, (111)In-bz-DOTA-Ki-4) were analysed further at 48 h and 72 h. RESULTS: All the RICs were successfully labelled with high specific activities (28-47 TBq/mmol) and sufficient radiochemical yields (>80%). Scatchard plot analysis proved high tumour affinity (KD = 20-220 nmol/l). In-vivo tumour accumulation in % of injected dose per g tissue (%ID/g) lay between 2.6 ((131)I-5F11) and 12.3 % ID/g ((131)I-Ki-4) with permanently high background in blood. Tumour/blood-ratios of all RICs were below one at all time points. CONCLUSIONS: In-vitro tumour cell affinities of all RICs were promising. However, in-vivo biokinetics tested in the mouse model did not meet expectations. This highlights the importance of developing and testing further new anti-CD30 conjugates.

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AIM: Graves' hyperthyroidism and antithyroid drugs empty the intrathyroid stores of hormones and iodine. The consequence is rapid 131I turnover and impending failure of radioiodine therapy. Can administration of additional inactive iodide improve 131I kinetics? PATIENTS, METHODS: Fifteen consecutive patients, in whom the 48 h post-therapeutically calculated thyroid dose was between 150 and 249 Gy due to an unexpectedly short half-life, received 3 x 200 microg inactive potassium-iodide (127I) daily for 3 days (Group A), while 17 consecutive patients with a thyroid dose of > or = 250 Gy (Group B) served as the non-iodide group. 48 hours after 131I administration (M1) and 4 or 5 days later (M2) the following parameters were compared: effective 131I half-life, thyroid dose, total T3, total T4, 131I-activity in the T3- and T4-RIAs. RESULTS: In Group A, the effective 131I half-life M1 before iodine (3.81 +/- 0.93 days) was significantly (p < 0.01) shorter than the effective 131I half-life M2 (4.65 +/- 0.79 days). Effective 131I half-life M1 correlated with the benefit from inactive 127I (r = -0.79): Administration of 127I was beneficial in patients with an effective 131I half-life M1 of <3 or 4 days. Patients from Group A with high initial specific 131I activity of T3 and T4 showed lower specific 131I activity after addition of inactive iodine compared with patients from the same group with a lower initial specific 131I activity of T3 and T4 and compared with the patient group B who was given no additional inactive iodide. This correlation was mathematically described and reflected in the flatter gradient in Group A (y = 0.5195x + 0.8727 for 131I T3 and y = 1.0827x - 0.4444 for 131I T4) and steeper gradient for Group B (y = 0.6998x + 0.5417 for 131I T3 and y = 1.3191x - 0.2901 for 131I T4). Radioiodine therapy was successful in all 15 patients from Group A. CONCLUSION: The administration of 600 microg inactive iodide for three days during radioiodine therapy in patients with Graves' hyperthyroidism and an unexpectedly short half-life of <3 or 4 days was a safe and effective alternative to the administration of a second radioiodine capsule.

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90Y-ibritumomab tiuxetan (Zevalin) is currently approved for radioimmunotherapy of patients with relapsed or refractory follicular non-Hodgkin's lymphoma pretreated with rituximab. Future directions are the combined use of 90Y-ibritumomab tiuxetan as part of the initial treatment and as first-line multi-agent therapy of relapsed disease. Current studies investigate patients with other than follicular indolent histologies, e. g. diffuse large cell lymphoma. Labelling of 90Y ibritumomab tiuxetan is a safe procedure, the radiochemical purity is not disturbed by a higher room temperature or by metallic impurity. Quality control is recommended by thin layer chromatography (TLC), strips >15 cm are favourable. TLC cannot distinguish between the correctly radiolabelled antibodies and radiocolloid impurity. If necessary, additional HPLC should be performed. Radiocolloid impurities are absorbed to the solid phase and do not reach the eluate. If the radiochemical purity test is insufficient (<95%), the additional cleaning using EconoPac 10 DG columns (Biorad, Hercules, CA, USA) is a reliable procedure to reduce the percentage of free radionuclide. However, this procedure is not part of the approval.

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Today, diagnostic and therapeutic strategies of Hodgkin lymphoma (HL) with positron emission tomography and radioimmunotherapy include state-of-the-art nuclear medicine which require the cooperation between oncology and nuclear medicine. The benefit of FDG-PET in HL patients with residual tumor masses consists of its high negative predictive value in the therapy control of the disease. The concept of waitful watching in patients with PET-negative residual masses after BEACOPP-chemotherapy will be evaluated in a large multicenter trial of the GHSG (German Hodgkin Study Group). Radioimmunotherapy has been performed in patients with CD20-positive Non-Hodgkin lymphoma for 10 years with promising results. HL is also an excellent target for immunotherapy due to the expression of antigens such as CD25 and CD30. Thus, a new radioimmunoconstruct consisting of the murine anti-CD30 antibody Ki-4 labeled with iodine-131 was developed for patients with relapsed or refractory HL.

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The effects of high cervical spinal cord stimulation (cSCS) on regional cerebral blood flow (rCBF) were investigated after experimentally induced subarachnoid haemorrhage (SAH) in rats by the means of (99m)Tc-HMPAO. The experiments were carried out on a total of 24 Wistar rats, divided in three groups [group I: control without SAH, group II: SAH, group III: SAH and cSCS]. (99m)Tc-HMPAO was administered intravenously (group II/group III) 48 hours after induction of SAH. In group III, (99m)Tc-HMPAO was given after 3 hours of cSCS. All animals were sacrificed 30 minutes after application on (99m)Tc-HMPAO. Radioactivities were determined in blood, cerebrum and cerebellum. The ratio cerebrum/blood and cerebellum/blood was calculated to ascertain "extraction rate" in the sample differentially. The following mean values were calculated for the cerebellum/blood ratio: Group I: 1.06, SD: 0.21; Group II: 0.66, SD: 0.21; Group III: 1.00, SD: 0.37. Comparing the mean values a highly significant difference could be found between group II and III (p = 0.007) and between group I and II (p = 0.0019), respectively. Calculations of the cerebrum/blood ratio revealed similar results. After SAH cSCS enhances cerebral and cerebellar blood flow in rats. Possibly, cSCD constitutes a new therapeutic approach in the treatment of disturbed regional cerebral blood flow after SAH.

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Clinical interest in laser-induced fluorescence (LIF) spectroscopy and photodynamic therapy (PDT) is growing rapidly and may ultimately lead to close parallel use of these techniques. However, variations in LIF due to photosensitizer retention as well as tissue damage and healing processes may interfere with autofluorescence-based diagnostic methods. We have investigated the compatibility of these two techniques by quantifying PDT-induced changes in LIF in the human esophagus. Fluorescence spectra were collected endoscopically at excitation wavelengths (lambda ex) of 337, 400 and 410 nm in 32 patients. Measurements were performed immediately before and after PDT treatment with porfimer sodium and during follow-up procedures. In the months following PDT regions of reepithelialized squamous showed reduced autofluorescence in comparison with untreated squamous regions (P = 0.0007). Photosensitizer fluorescence was undetectable with lambda ex = 337 nm during follow-up procedures, whereas for lambda ex = 400 and 410 nm porfimer sodium fluorescence was noted for nearly a year after treatment. Therefore, residual photosensitizer fluorescence is likely to affect certain LIF-based diagnostic techniques during a period when patients are at high risk for tumor recurrence. Modification of LIF systems and/or the use of alternative photosensitizers may be required to optimize the detection of lesions in the post-PDT patient. Given the potential of LIF as a method for surveillance following cancer therapy, further investigation of the compatibility of specific LIF approaches with cancer pharmaceuticals may be warranted.

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It could be demonstrated that cervical spinal cord stimulation increases cerebral blood flow. The effects of electrical stimulation of the trigeminal ganglion in the acute phase of SAH in pigs were investigated. The experiments were carried out on 11 domestic pigs divided in two groups (group I: SAH [n = 5]; group II: SAH and trigeminal stimulation [n = 6]). In all animals a native SPECT was performed. The Gasserian ganglion was exposed for inserting the stimulation electrode. SAH was induced by injecting 10 ml autologous blood through a catheter placed in the suprasellar cistern. 30 minutes after SAH-induction electrical stimulation was started for two hours in group II (2.8-4.5 V, 50 Hz, 300 microseconds). 99mTc-HMPAO (400-540 MBq) was injected intravenously 110 minutes later. In group I 99mTc-HMPAO was applied after the same time interval. 80 minutes later SPECT was performed. Data were processed to calculate the uptake of radioactivity (%/kg tissue weight). The mean values were calculated for the different groups: native animal examination (%/kg tissue weight): 0.6343; group I: 0.468; group II: 0.6533. Comparing the mean values a highly significant difference between group I and group II (p < 0.01) and between native examination and group I (p < 0.01) could be found. No statistical significance could be detected on comparing the left/right-ratio in any ROI. The electrical stimulation of the Gasserian ganglion leads to a significantly increased uptake of 99mTc-HMPAO after induced SAH. Maybe the stimulation of the Gasserian ganglion constitutes a new therapeutic modality treating disturbed rCBF after SAH.

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AIM: The change of both amount and chemical forms of radioiodine exhaled in the air of rooms with patients on the therapy ward should be investigated depending on radioactivity applied, time after application, and kind of thyroid disease. METHODS: The air of ward-rooms of 62 patients with thyroid carcinoma, Graves' Disease, and autonomy which received different therapy doses, was investigated with an portable constant air flow sampler. Different chemical iodine species (organic, elemental, aerosol bound) were collected during 8 hr in various filters until 3 days after application of the radioiodine capsule, according to their chemical form. The radioactivity in the filters was measured with a well counter on defined time points after application. RESULTS: The radioactivity exhaled was between 0.008 and 0.03% related to activity of radioiodine applied. The percentage of radioiodine exhaled related to the activity applied, differed significantly depending on disease and changed as follows: Grave's Disease > autonomy > carcinoma. The exhalation of radioiodine became stronger with increasing applied activities and showed an exponential decrease with time. The most part of radioiodine was present in organic bound form. This organic portion decreased with time in favour of the other iodine species. CONCLUSION: The degree of accumulation of radioiodine orally applied within thyroid seems to be in direct proportion to the extend of its exhalation. Further measurements directly in the breathing air of RIT-patients are necessary, in order to clarify the relationship between degree of thyroid uptake and quantity as well as chemical form of radioiodine exhaled.

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The search for new radiopharmaceuticals for tumour diagnosis usually proceeds on the basis of rational concepts drawing on the latest advances in molecular biology. Using this approach, radioactive peptide hormones, antibodies and oligonucleotides have been developed that are used increasingly in nuclear medicine for diagnostic and therapeutic purposes. This article, however, focusses on a group of radiopharmaceuticals whose use in tumour diagnosis was not the outcome of a methodical development programme but rather the result of a chance discovery. These radiopharmaceuticals, thallium-201 and technetium-99m labelled 2-methoxyisobutylisonitrile (MIBI), tetrofosmin and furifosmin, were first developed through extensive research efforts for cardiac imaging, but during their worldwide application for myocardial scintigraphy they were accidentally found to accumulate in tumours. Intensive studies were then begun on cell cultures in an attempt to discover the cause of their uptake into tumours. The aim was to compare the effectiveness of the radiopharmaceuticals for tumour diagnosis in a range of indications and to investigate the various mechanisms by which they are taken up into tumours. While the more favourable radiophysical properties of 99mTc-MIBI render it superior to 201Tl for many diagnostic purposes, neither 99mTc-tetrofosmin nor 99mTc-furifosmin has yet proved suitable for clinical routine examinations, although the former has found limited application. In the case of 99mTc complexes, the breakthrough came with the experimental finding that these substances are substrates of P-glycoprotein, a product of the human multidrug resistance gene (MDR1). The concentration of 99mTc complexes in tumour cells is a function of a passive, membrane potential-dependent influx into and a P-glycoprotein-controlled efflux out of the tumour cell. Preliminary studies suggest that in vivo detection of MDR may even be possible. There is also evidence that the P-glycoprotein-mediated transport system can be blocked competitively. However, it will be some time before a system can be developed for detection of MDR on a routine basis.

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AIM: It should be shown, that it is possible to insert radioactive isotopes of Yb and Y into some selected porphyrins. Besides, first informations about the biodistribution of Yb-169-por-phyrin-complexes should be obtained. METHODS: Carrier added radioactive isotopes were used for the synthesis of the metal porphyrin complexes. The animal experiments were done with mamma carcinoma bearing mice. The activity of the organs was determined 5 and 24 h after i.v. injection in a well counter. RESULTS: Four Yb-169-porphyrin complexes and Y-90-porphyrin complexes could be synthesized in non-carrier-free form. This was verified by absorption spectra, TLC and HPLC. Depending on the complex, the average tumour/background ratios were between 2 and 20. CONCLUSION: The synthesized radioactive metal-porphyrin complexes showed a clear tumour-affinity which could be used for tumour scintigraphy or perhaps therapy if the synthesis is improved (goal: reduction of carrier, other radionuclides).

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BACKGROUND: An accurate assessment of deep dermal burns within the first week after burn is still an unresolved clinical problem. Infrared-excited fluorescence of indocyanine green was examined as a method of early determination of burn depth. METHODS: Burns of varying depths were placed on the paraspinal region, flank, and abdomen of swine using a heated brass block. Fluorescence images of the burns were recorded 1, 24, 48, and 72 hours later. RESULTS: The ratio of fluorescence in 64 burn wounds relative to adjacent normal tissue identified wounds that healed and did not heal within 21 days with an accuracy of 100%, after accounting for the age of the burn. Higher fluorescence ratios were observed in newly placed burns relative to older burns having comparable depths. CONCLUSION: Deep partial-thickness burns were differentiated from deep dermal full-thickness burns in a porcine skin burn model independent of body location. Diagnosis was possible between 1 and 72 hours after injury.

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OBJECTIVE: To report the results of a clinical study investigating the diagnosis of malignant and dysplastic bladder lesions by protoporphyrin IX (PPIX) fluorescence and to compare them with those from earlier studies. PATIENTS AND METHODS: The study included 55 patients with suspected bladder carcinoma (at initial diagnosis or at tumour follow-up visits); 130 bladder biopsies from 49 patients were classified by pathological analysis. All patients received an intravesical instillation of 50 mL of a 3% 5-aminolaevulinic acid (ALA) solution a mean of 135 min before cystoscopy, which was then performed under white and blue light. Malignant/dysplastic lesions showing red fluorescence under blue-light excitation were noted and the increase in detection rate calculated. RESULTS: There were 63 benign and 67 malignant/dysplastic areas biopsied; 10 malignant/dysplastic lesions (four transitional cell carcinoma, two carcinoma in situ, four dysplasia) were not detected during routine white-light cystoscopy but were identified under blue light. Fluorescence cystoscopy improved the overall diagnosis of malignant/dysplastic bladder lesions by 18% over standard white-light cystoscopy. The improvement was greater for dysplastic lesions and carcinoma in situ (50%). However, the improvement over standard cystoscopy was less than that found by other groups. CONCLUSION: The ALA-based fluorescence detection system significantly enhanced the diagnosis of malignant/dysplastic bladder lesions. However, determining the optimum drug exposure time requires further investigation using well-characterized instrumentation and study protocols, which would then allow comparison of the results from different groups.

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BACKGROUND: The spectral irradiance delivered by a variety of gastrointestinal endoscopes was measured as a function of wavelength and used to estimate the amount of light delivered to the mucosal surface during routine endoscopic procedures. METHODS: Spectral irradiances from seven different endoscopes were measured using a commercial spectroradiometer calibrated against a National Institute of Standards and Technology traceable source. RESULTS: The largest maximum irradiance was 8.0 W/cm2 obtained from an endoscope used in transillumination mode. In the typical viewing mode, the largest maximum irradiance measured was 1.6 W/cm2. The majority of the light energy delivered by these gastrointestinal endoscopes was in the visible wavelength region (400 to 700 nm). DISCUSSION: The measurements revealed surprisingly high light exposures in the visible wavelength range. In fact, the estimated tissue exposures can exceed by 40-fold the standards established for skin exposure to light set forth by the American National Standards Institute. Because gastrointestinal endoscopy is widely viewed to be safe, it is probable that the gastrointestinal tract has significant tolerance to light exposure.

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BACKGROUND: Scanning, high-powered carbon dioxide laser ablation of eschar may facilitate blood conservation in patients with burns. METHODS: Twenty-one children with full-thickness burns that required serial excisions were enrolled in a Human Studies Committee approved protocol in which a full-thickness wound was ablated with a rapidly scanned continuous wave carbon dioxide laser system. A control wound was sharply excised, and both wounds were immediately autografted. End points were engraftment at 7 days and serial Vancouver scar scores. RESULTS: The children had an average age of 8.3 +/- 1.2 years, weight of 36.3 +/- 4.9 kg, and burn size of 40% +/- 5.1%. The study wounds were ablated with an average energy of 99.2 +/- 5.7 W; there was no bleeding from 19 successfully ablated wounds. Initial engraftment averaged 94.7% +/- 3.5% in the control sites and 94.7% +/- 3.3% in the study sites (P = 1.0). There was no significant difference in Vancouver scar scores at an average follow-up of 32.0 +/- 5.2 weeks. CONCLUSIONS: This pilot study follows a successful trial of this concept in a porcine model and demonstrates the technical feasibility of laser vaporization of burn eschar in humans with immediate autografting. Further refinement of the technique is required before it can be generally recommended.

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The effect of fluence rate and light fractionation on phototoxicity was investigated in vivo in an orthotopic rat bladder tumor model. Two photosensitizers, benzoporphyrin derivative monoacid ring A and 5-aminolevulinic acid-induced protoporphyrin IX, were studied. For a given cumulative light dose of 30 J/cm2, enhanced tumor destruction was observed from both photosensitizers when using either lower fluence rates or fractionated light delivery. Photobleaching experiments in vivo demonstrated that the photobleaching rate, however, was not fluence rate dependent. The fluence rate and light fractionation effects on tumor phototoxicity lead to rapid local depletion in oxygen concentration that inhibited subsequent photochemical reactions necessary for efficient photodestruction of tumor cells. Nicotinamide did not enhance photodynamic therapy efficacy, suggesting that the added increase of oxygen within the tumor was not sufficient to enhance photodestruction of hypoxic cell fractions. The independence of the photobleaching rate with fluence rate suggests distinct mechanisms, at least in part, of photodestruction of the tumor and the photosensitizer and that the rate of photosensitizer photo-bleaching may not always be an appropriate monitor for singlet oxygen availability and photodynamic therapy dosimetry.

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