[Hybrid imaging in diagnostics and therapy of chronic myocardial ischemia. Clinical value]. / Hybridbildgebung in Diagnostik und Therapie der chronischen Myokardischämie. Klinischer Stellenwert.

Clinical studies have consistently shown that there is only a very weak correlation between the angiographically determined severity of coronary artery disease (CAD) and disturbance of regional coronary perfusion. On the other hand, the results of randomized trials with a fractional flow reserve (FFR)-guided coronary intervention (DEFER, FAME I, FAME II) showed that it is not the angiographically determined morphological severity of coronary artery disease but the functional severity determined by FFR that is critical for prognosis and the indications for revascularization. A non-invasive method combining the morphological image of the coronary anatomy with functional imaging of myocardial ischemia is therefore particularly desirable. An obvious solution is the combination of coronary computed tomography angiography (CCTA) with a functional procedure, such as perfusion positron emission tomography (PET), perfusion single photon emission computed tomography (SPECT) or perfusion magnetic resonance imaging (MRI). This can be performed with fusion imaging or with hybrid imaging using PET-CT or SPECT-CT. First trial results with PET CCTA and SPECT CCTA carried out as cardiac hybrid imaging on a 64 slice CT showed a major effect to be a decrease in the number of false positive results, significantly increasing the specificity of CCTA and SPECT. Although the results are promising, due to the previously high costs, low availability and the additional radiation exposure, current data is not yet sufficient to give clear recommendations for the use of hybrid imaging in patients with a low to intermediate risk of CAD. Ongoing prospective studies such as the SPARC or EVINCI trials will bring further clarification here.

[Therapy of malignant ascites in vivo by 211At-labelled microspheres]. / Therapie maligner Asziteszellen in vivo mit 211At-markierten Mikrosphären.

AIM: Determination of the biological effect of the alpha emitter (211)At on cellular level as well as the assessment of dosimetric data in a tumour model in vivo. METHODS: Transplantation of malignant ascitic cells in mice intraperitoneally and estimation of tumour characteristics (doubling time of the cells, mean survival of the animals following an i.p. application of a defined tumour cell number). (211)At labelled human serum albumin microspheres B-20 (MSP) of varying activity were injected into tumour bearing mice intraperitoneally. The effectiveness of the therapy was evaluated by means of determination of the duration of cell cycle arrest as well as the microscopic analysis of the rate of abnormal mitotic cells due to radiation induced damage. Furthermore, dose dependence of survival was evaluated. RESULTS: Three days following the intraperitoneally application of 8 x 10(6) tumour cells, 50-600 kBq (211)At-MSP were applied into the abdominal cavity. Considering the volume of ascites at this time and the administered activity, dose calculations were performed. An activity of 50 kBq caused a dose of 0.84 Gy. The increase of radiation induced effect on ascitic tumour cells was correlated with the dose. Between the duration of the cell cycle arrest and the administered activity, a directly proportional correlation was found. The mean survival of non-treated animals was 16.9 +/- 3.7 days. The prolongation of the survival was proportional to the activity administered. Using a dosage of 10 Gy, five animals out of 16 survived. CONCLUSION: Therapy of malignant ascitic cells using (211)At-MSP was effective in vivo. For tumour therapy, the (211)At represents a highly effective alternative to usually applied beta emitters.

Persistent vegetative state: evaluation of brain metabolism and brain perfusion with PET and SPECT.

Patients in persistent vegetative state (PVS) after severe head trauma were investigated with 99mTc-ECD SPECT and 18F-FDG PET to further characterize the degree of brain damage and to obtain insight into changes of brain perfusion and glucose metabolism. 18F-FDG PET and 99mTc-ECD SPECT were performed in 16 patients in PVS. Quantitative PET data were compared with that obtained from seven normal controls. After spatial normalization into Talairach space, global grey matter values and regional data using predefined ROI sets were derived. For comparison of PET and SPECT, regional data were normalized to their individual mean grey matter values. Patients in PVS showed significantly lower values of cerebral glucose metabolism than did the controls. The mean reduction of grey matter values in cortical and subcortical structures was 58%, except in the vermis cerebelli, where only a reduction of 16% was found compared to the controls. Comparing the glucose metabolism and perfusion within the patient group, the pattern of both modalities was similar in the neocortex and internal ganglia. In the cerebellar hemispheres a relatively higher perfusion than glucose metabolism was found. The overall reduction of 58% of glucose metabolism in grey matter structures is in accordance with other PET studies investigating PVS patients with different disease histories. The relative preserved activity of vermis cerebelli seems to be an uncommon finding not described by other authors up to now.

3-O-methyl-6-[18F]fluoro-L-DOPA and its evaluation in brain tumour imaging.

3-O-Methyl-6-[(18)F]fluoro-L-DOPA (OMFD) is a major metabolite of 6-[(18)F]fluoro-L-DOPA. Although synthesis of OFMD was primarily established to study the dopaminergic system, as it is an amino acid analogue, uptake in experimental tumours has been found. The aim of this study was to evaluate the applicability of OMFD for brain tumour imaging and to obtain initial estimates of whole-body biodistribution and radiation dosimetry in humans. Nineteen patients with suspected or confirmed brain tumours were investigated with OMFD and dynamic brain PET, complemented by whole-body PET in seven patients. Tracer kinetics were compared for normal brain and intracerebral lesions. Tissue accumulation was quantified with standardised uptake values (SUVs). Whole-body distribution in combination with tracer kinetics from animal experiments was used for the calculation of radiation dosimetry data. On the basis of OMFD PET, viable brain tumour was suspected in 16 patients with SUVs of 3.0+/-0.8 and a tumour to non-tumour ratio of 1.9+/-0.5. Highest tumour and normal brain uptake occurred between 15 and 30 min, with a subsequent slow decrease. Late whole-body tracer distribution was uniform without specific organ accumulation. Elimination occurred via urine. The mean radiation dose to the whole body was estimated at 0.016 mSv/MBq, with the kidneys as dose-critical organ (0.033 mGy/MBq). In conclusion, OMFD enables the visualisation of brain tumours with SUVs similar to other fluorinated amino acids. The whole-body radiation exposure from OMFD is comparable to that from FDG imaging.

[Predictive value of thyrotropin receptor antibodies using the second generation TRAb human assay after radioiodine treatment in Graves' disease]. / Prädiktiver Wert der Thyreotropinrezeptor-Antikörper bei Bestimmung im TRAK-human-Assay der zweiten Generation nach Radioiodtherapie des Morbus Basedow.

UNLABELLED: The detection of TSH-receptor antibodies (TRAb) in patients with Graves' disease is routinely used in nuclear medicine laboratories. This determination has been possible for approximately 3 years with a second generation human TRAb assay. Studies showed that this TRAb determination is diagnostically more sensitive compared to established, porcine TRAb assays. OBJECTIVE: The aim of our study was to investigate, based on a ROC analysis, whether TRAb determination with the new, second generation assay allows a dependable statement about probability of occurrence of relapse after radioiodine therapy in patient suffering from Graves' disease. METHODS: 57 patients were examined with the DYNOtest TRAKhuman (BRAHMS Diagnostica AG, Hennigsdorf) directly before and six months after therapy with radioiodine (dose: 150 Gy). A ROC-analysis was performed to determine positive/negative predictive values depending on different cut-off values. RESULTS: Whereas 21/57 patients became eu- or hypothyroid after six months, 36/57 patients relapsed. Non-relapsed patients showed a significant lower median TRAb titer (4.2 IU/l vs. 19.2 IU/l; p <0.05) compared to relapsed patients. But the positive predictive value conducted 63 and 66, 62 and 66 as well as 63 and 69% (before and after therapy) linked with the cut-offs 1.0, 1.5, and 2.0 IU/l. So it was in areas also achieved by the first generation porcine radio receptor assay. CONCLUSION: An increased sensitivity is achieved undoubtedly with the new DYNOtest TRAKhuman in the diagnostic of Graves' disease. It is not held over the established radio receptor assay concerning the positive predictive value for relapsing patients.

Renaissance of 224 Ra for the treatment of ankylosing spondylitis: clinical experiences.

Radium (224Ra) is commercially available again for the treatment of ankylosing spondylitis. Twenty patients suffering from ankylosing spondylitis were treated with weekly intravenous (i.v.) injections of 1 MBq 224Ra for 10 weeks. Therapeutic effect was measured by C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and full blood count, as well as a completion of the Bath ankylosing spondylitis functional index (BASFI) questionnaire. Follow-up was done after three and six months. At the end of the treatment course pain and movement restrictions had improved subjectively in 12 out of 20 patients. These patients were also able to discontinue or reduce their analgesic or anti-inflammatory medications. Subjective improvement was well correlated with a reduction of CRP by 45% and BASFI by 73%. At the six-month follow-up, ten patients reported a lasting improvement, whereas two had suffered a relapse. A late therapeutic response after three months was seen in a single patient only. Patients who did not respond to radium had lower initial levels of acute-phase reactants and peripheral joint involvement. Only mild side-effects, e.g. temporary worsening of pain, were observed. Leukocytes and platelets reversibly decreased by 25%, respectively. It is concluded that 224Ra is an effective and safe treatment for ankylosing spondylitis.

[Recovery test or immunoradiometric measurement of anti-thyroglobulin autoantibodies for interpretation of thyroglobulin determination in the follow-up of different thyroid carcinoma]. / Wiederfindungstest oder immunradiometrische Bestimmung der Autoantikörper gegen Thyreoglobulin zur Interpretation der Thyreoglobulinbestimmung in der Nachsorge des differenzierten Schilddrüsenkarzinoms.

UNLABELLED: The determination of thyroglobulin (Tg) in the follow-up of differentiated thyroid carcinomas (DTC), is routinely used in nuclear medicine, although some problems, like a disturbed recovery-test (RT) or autoantibodies to thyroglobulin (TgAb), are well known. But it is a controversial issue in literature, whether the determination of TgAb should be performed beside or instead of the RT. OBJECTIVE: The study compares the clinical value of the determination of both TgAb and RT with sensitive assays. METHODS: 356 patients (pts) were investigated. The results were compared to the concentration of Tg in the sera of the pts. 288 pts stayed tumor-free, the remaining 68 pts showed a recurrence (local and/or metastatic) of their DTC. We measured Tg (with RT) using an immunoradiometric assay (Tg-IRMA; SELco Tg; Fa. Medipan Diagnostica GmbH) and TgAb using a direct assay (CentAK anti-Tg; also from Fa. Medipan). RESULTS: The prevalence of TgAb, and of disturbed RT respectively, in the whole population of DTC-pts was 7.6%, in the subgroup of tumor-free pts 6.6%, and in the remaining pts with tumor-recurrence 11.8%, respectively 2.0%, 1.7% and 2.9%. In a significantly higher percentage of pts with local/metastatic recurrence, both a positive TgAb (p < 0.001) and a disturbed RT (p < 0.05) were found. 7/68 pts with tumor-recurrence but Tg < 1 ng/ml showed positive TgAb, only 2/7 had a disturbed RT. In this group, no patient with Tg > 1 ng/ml demonstrated either positive TgAb or disturbed RT (p < 0.001 and p < 0.05). CONCLUSION: The determination of TgAb in the follow-up of DTC is necessary, because it supports a suspicion to tumor-recurrence in pts with negative Tg. Also the RT is of great value because of a possibly High dose hook-effect.

A high-sensitivity enzyme-linked immunosorbent assay for serum thyroglobulin.

A sensitive enzyme-linked immunosorbent assay (ELISA) for measuring serum thyroglobulin (Tg) is described. The assay has a functional sensitivity of 0.03 ng/mL and values obtained in sera from patients with treated differentiated thyroid cancer (DTC; n = 24, 17 of whom showed some evidence of recurrence) and from healthy blood donors (n = 48) were in agreement with those obtained by Tg immunoradiometric assay (IRMA) (functional sensitivity = 0.6 ng/ml) (r = 0.99 and 0.98 for the two groups, respectively). The Tg levels measured by ELISA in 47 of the healthy blood donor sera ranged from 2.3 to 139 ng/ml with 1 serum giving a value of 0.03 ng/mL. The mean +/- standard deviation (SD) Tg concentration for the healthy blood donors was 20.3+/-23 ng/mL. Studies with a recovery test suggest that Tg measurements by ELISA were not always reliable when Tg autoantibodies were present. Analysis of samples from 167 patients treated successfully for DTC (papillary carcinoma, 94; follicular carcinoma, 73) showed that 139 were negative for Tg autoantibodies and of these 106 (76%) had Tg levels measurable by ELISA (0.03 ng/mL or greater). In contrast, only 7 (5%) of these 139 sera had Tg levels measurable by IRMA (0.6 ng/mL or greater). It is possible that this ability to measure Tg simply and easily in most treated DTC patients will have significant advantages for patient care. In particular, the Tg level after initial ablative treatment will usually be measurable rather than undetectable. Furthermore, any increases in serum Tg levels which may herald relapse will be detectable earlier.

Accuracy of the intra-operative radioguided localization of the sentinel lymph node (SLN) 24 hours after lymphoscintigraphy in patients with malignant melanoma.

AIM: For optimized logistics for the sentinel lymphadenectomy (SL) it might be helpful for the clinics involved if a longer time period between the lymphoscintigraphy (LS) and surgery is possible. Therefore, we investigated if a precise localization of the sentinel lymph node is possible 24 hours after LS. METHODS: 78 patients with primary malignant melanoma (MM; n = 44) or with MM pre-operated by excisional biopsy (n = 34) were investigated. In 40 cases the tumor was localized on the trunk and in 38 cases on the extremities. Mean MM thickness was 2.68 mm (range: 0.29 to 12 mm). In all patients a lymphoscintigraphy (LS) with an average of 85 MBq of Tc-99m nanocolloid was performed one day prior to surgery. Immediately after tracer application dynamic data acquisition was started at a LFOV gamma camera followed by a whole body scan. With a hand-held gamma detector (C-Trak) 2, 4, 6, 8, and 24 hours after tracer administration the SLN was identified and the counts registered. RESULTS: 94 SLNs were identified in 87 lymphatic basins from which 86 could be resected. Nine MM showed two draining channels. After 24 hours 15.5% (as an average) of the initial counts could be measured in the SLN. The uptake in the SLN in pre-operated versus patients with primary tumor was statistically not significant (p = 0.4). In 16 cases (20.5%) the SLN was tumor positive. Four of those patients developed distant metastases and two died within the first year. None of the patients with negative SLN developed distant metastases or died. CONCLUSION: The remaining activity in the SLN up to 24 hours after administration is sufficient for their intra operative localization. The method of lymphoscintigraphy and localization of the SLN by a hand-held gamma detector optimizes the intra operative identification of the SLN in patients with malignant melanoma.

[Prevalence of goiter and iodine deficiency in Saxony is less than previously assumed. A study 6 years after discontinuation of general iodization of table salt]. / Strumaprävalenz und Joddefizit in Sachsen geringer als bisher angenommen. Eine Untersuchung sechs Jahre nach Abschaffung der generellen Speisesalzjodierung.

BACKGROUND: Germany is a known area of goitre endemicity. In East Germany (former German Democratic Republic), iodization of pre-packed table salt was introduced in 1985 and was only abolished after German reunification in 1990. Public awareness campaigns have concentrated on the use of iodized salt in the products of bakers and butchers as well as canned and frozen food since. Reports in the literature give figures of goitre prevalence (13 to 69%) inconsistent with each other and with our own clinical experience (about 30%). METHOD: We undertook a prospective cross-sectional study with a non randomly selected population (craftsmen and -women) covering Saxony in 1996, 1,129 and 1,594 adults were examined in 1996 and 1997, respectively, using a questionnaire, ultrasound, and measurement of urinary iodine excretion (1996 only). RESULTS: We found the following (mean) results in men/women in 1996: thyroid volume 23.0 +/- 1.3/17.1 +/- 1.5 ml, prevalence of goitre 32.1/31.3%, prevalence of thyroid nodules 21.1/23.0%, urinary iodine excretion (per creatinine) 86.4 +/- 1.3/104 +/- 24.1 nmol/mmol (97.1 +/- 1.4/117 +/- 27.1 micrograms/g). In 1997 the results were as follows: thyroid volume 20.9 +/- 1.2/15.7 +/- 2.1 ml, prevalence of goitre 25.6/23.6%, prevalence of thyroid nodules 16.4/19.8%. CONCLUSION: Whilst goitre and iodine deficiency are still endemic in Saxony, both have been improving despite the abolition of general table salt iodization.

Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin's disease and non-Hodgkin's lymphoma.

The prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the assessment of post-treatment residual masses in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphomas (NHL) was evaluated. We prospectively studied 58 patients with HD (n = 43) or NHL (n = 15) who had post-therapeutic complete remission with residual masses (CRu) indicated by computerized tomography. Analysis of 62 residual locations by FDG-PET was performed separately for HD and NHL. Patients with a PET-positive residual mass [standardized uptake value (SUV) > 3] had a recurrence rate of 62.5% (5/8 patients), whereas patients with PET-negative residual mass (SUV < or =3.0) showed a recurrence rate of 4% (2/50 patients, P = 0.004). A positive FDG-PET study correlated with a significantly poorer progression-free survival (P < 0.00001). No recurrence occurred in any of the 39 HD patients with a negative PET scan (negative predictive value, 100%). Four out of four NHL patients with a positive PET study relapsed (positive predictive value, 100%). In conclusion, FDG-PET is a suitable non-invasive method with a high degree of accuracy in the prediction of early recurrence in lymphoma patients with CRu.

18F-FDG for the staging of patients with differentiated thyroid cancer: comparison of a dual-head coincidence gamma camera with dedicated PET.

Coincidence imaging with a dual-head gamma camera may offer a cost-effective alternative to dedicated PET. The aim of this study was to compare the diagnostic accuracy of coincidence imaging and PET in patients with differentiated thyroid cancer. Thirty-one patients were studied after thyroidectomy and radioiodine ablation. They were injected with a single dose of 300 MBq 18F-FDG. Scanning was performed on a dedicated PET system after 1 hr, and on a coincidence gamma camera after 4 hrs. Based on a lesion-by-lesion comparison, coincidence imaging and PET concurred in 69% of 118 lesions. Based on lesion size, concurrence was 96% in lesions larger than 1.5 cm, and 62% in those between 1 and 1.5 cm. Lesions smaller than 1 cm could not be identified with coincidence imaging. Identical staging was obtained with coincidence imaging and PET in 26/31 patients (84%). In four patients FDG accumulating lesions were shown by both the coincidence camera and the dedicated scanner, but not detectable with any other imaging means and were confirmed histologically on surgery. Although a coincidence camera is technically inferior to a dedicated PET scanner, it may provide clinically useful results in situations were a lesion of sufficient size and FDG uptake is to be expected, e.g. when evaluating a known lesion for malignancy.

[Comparison of rhenium-188, rhenium-186-HEDP and strontium-89 in palliation of painful bone metastases]. / Vergleich von Rhenium-188-HEDP, Rhenium-186-HEDP und Strontium-89 für die palliative Schmerztherapie von Skelettmetastasen.

AIM: Several radiopharmaceuticals were compared previously with regard to the efficiency in pain palliation of bone metastases. Furthermore, first results were reported on the suitability for such kind of therapy of the generator produced radionuclide rhenium-188. METHOD: Influence of Rhenium-188-HEDP (Re-188), Rhenium-186-HEDP (Re-186) and Strontium-89 (Sr-89) on pain symptoms and bone marrow function were obtained in 44 patients (pts). These were 16 pts. with Re-188 (2943 +/- 609 MBq), 13 pts. with Re-186 (1341 +/- 161 MBq) and 15 pts. with Sr-89 (152 +/- 18 MBq) (6 woman with breast cancer and 38 men with prostata cancer). RESULTS: 81 of pts. after Re-188, 77% after Re-186 and 80% after Sr-89 reported relief of pain. The Karnofsky-Index established by pts. increased from 74 +/- 9% to 85 +/- 11% after Re-188, from 70 +/- 11% to 76 +/- 11% after Re-186 and from 62 +/- 10% to 69 +/- 10% after Sr-89. However, the difference between the pre- and the post-therapeutic value is only statistically significant in the case of Re-188 therapy (p = 0.001). A decrease of platelets of 30 +/- 14% after 2.8 +/- 0.7 for pts. treated with Re-188, of 39 +/- 20% after 3.7 +/- 1.0 weeks for pts. treated with Re-186 and of 34 +/- 26% after 4.4 +/- 1.0 weeks for pts. treated with Sr-89 compared to the value before therapy was observed. The difference was not significant between the 3 groups of pts. (p = 0.125 to 0.862). CONCLUSION: All tried radiopharmaceuticals were effective in pain palliation. The various radionuclides had no significant difference in the pain relief or the bone marrow impairment. If only the Karnofsky-Index after Re-188 HEDP seems to be a little more increase.

Significant reduction of the mass of bone metastasis 1 year after rhenium-186 HEDP pain palliation therapy.

A 59-year-old man with prostate cancer and pain from multiple bone metastases was treated with 1,424 MBq (38.5 mCi) rhenium-186 hydroxyethylidene diphosphonate (Re-186 HEDP). In addition, he had nonsteroidal antiandrogen, progestagen, and an analog-luteinizing hormone. Neither chemotherapy nor external-beam radiotherapy was administered. Bisphosponate therapy was stopped 4 weeks before the administration of Re-186 HEDP. The Tc-99m HMDP whole-body scan obtained 6 weeks after therapy showed the same results as before therapy. However, 1 year after therapy, a significant reduction of the mass of the metastases was visible on bone scan. The bone scan index decreased from 34 before therapy to 10 after 1 year. The patient described significant pain relief and stopped his analgesic intake 3 weeks after therapy.

[Measurement of thyrotropin receptor antibodies (TRAK) with a second generation assay in patients with Graves' disease]. / Die Bestimmung von Thyreotropin-Rezeptor-Antikörpern (TRAK) mit einem Assay der zweiten Generation bei Patienten mit Morbus Basedow.

AIM: The detection of TSH-receptor-antibodies (TRAb) in patients (pts) with Graves' disease (GD) is routinely used in nuclear medicine laboratories. It is performed by commercial, porcine radioreceptorassays (RRA) measuring TSH binding inhibitory activity. A second generation assay using the human, recombinant TSH-receptor was developed during the last years. The manufacturer composed this new assay as a coated tube RRA (CT RRA) and claimed a higher sensitivity for GD. METHODS: TRAb was measured in 207 pts with various thyroid disorders and 205 healthy controls using the new coated tube RRA (Fa. B.R.A.H.M.S. Diagnostica GmbH, Berlin, Germany) as well as a conventional RRA (Fa. Medipan Diagnostica GmbH, Selchow, Germany): 60 pts suffering from GD showing a relapse after antithyroid drug treatment and before radioiodine therapy, 109 pts with disseminated autonomia (DA) and 38 pts suffering from Hashimoto's thyroiditis. A ROC-analysis was performed to find the optimal decision threshold level for positivity. RESULTS: We found 42/60 TRAb-positive pts with GD in the established RRA (threshold 6 U/L) and 52/60 in the CT RRA, respectively. The sensitivity increased from 70% (RRA) to 86.7% (CT RRA). The CT RRA found 2 false positives (one Hashimoto's and one healthy control) and the RRA detected 3 Hashimoto's and 2 healthy controls as false positive. CONCLUSION: The increased sensitivity of CT RRA for GD provides an advantage compared to conventional RRA, especially in GD-patients relapsing after antithyroid drug treatment. Functional sensitivity and Interassay-variation of CT RRA are very precisely compared to conventional RRA. Handling of the new assay is also improved.

Rhenium-188-HEDP in the palliative treatment of bone metastases.

INTRODUCTION: Rhenium-188-HEDP (188Re-HEDP) is a new and attractive radiopharmaceutical for the treatment of bone pain due to metastases. As a product of a 188W/188Re generator it is convenient for clinical use. With a short physical half life of 16.9 hours and a maximal beta-energy of 2.1 MeV, it is suitable for therapy. METHODS: We investigated the influence of 188Re-HEDP on pain relief, analgesic intake and impairment of bone marrow function in 15 patients. All patients were interviewed using standardized questions before, and 1, 2, 3, 4, 8, and 12 weeks after therapy. Blood samples were drawn weekly for 12 weeks, and a blood count was performed. Patients underwent gamma camera imaging to determine the radionuclide accumulation 4, 20, and 28 hours after therapy. The patients were treated with 1600 to 3459 MBq of 188Re-HEDP. RESULTS: Patients showed an improvement of the Karnofsky performance index from 74 +/- 8% to 84 +/- 11% 12 weeks after therapy. This improvement was statistically significant (p = 0.001). Eighty percent of the patients described pain relief and reduction of analgesics. Twenty percent of the patients could discontinue their analgesics. Mean platelet count decreased from (284 +/- 84)*10(3)/microliter to (205 +/- 62)*10(3)/microliter, and mean leukocyte count from (7.5 +/- 1.5)*10(3)/microliter to (5.9 +/- 2.1)*10(3)/microliter after therapy. The maximal differences between the values of platelets and leukocytes before and after therapy were not statistically significant (p = 0.021 and p = 0.094). Prostate specific antigen decreased from 95 +/- 83 ng/ml to 41 +/- 21 ng/ml, the difference was not statistically significant (p = 0.443). The bone accumulation 4, 20, and 28 hours after therapy was 1.3 +/- 0.5%, 0.6 +/- 0.3%, and 0.45 +/- 0.2% of the injected dose of a single metastasis, and 57 +/- 17%, 15.5 +/- 2% and 11 +/- 3% in the whole body, respectively. The effective half-life of 188Re-HEDP was 15.3 +/- 3.0 hours in the bone metastases, and 11.4 +/- 2.8 hours in the whole body. This corresponds to a residence time of 0.22 +/- 0.25 hours in the bone metastases, and of 10.54 +/- 2.59 hours in the whole body. CONCLUSION: In a small patient population, 188Re-HEDP therapy for bone pain palliation was effective and was associated with minimal toxicity.