Thyroid remnant dose: 124I-PET/CT dosimetric comparison of rhTSH versus thyroid hormone withholding before radioiodine remnant ablation in differentiated thyroid cancer.

AIM: Recombinant human thyroid-stimulating hormone (rhTSH) recently was approved as an alternative to thyroid hormone withholding (THW) to elevate TSH for thyroid remnant ablation in differentiated thyroid carcinoma patients. High ablation success rates are reported with diverse rhTSH-aided (131)I activities. Improved renal function causes approximately 50% faster radioiodine clearance under euthyroidism versus hypothyroidism. Knowledge of comparative remnant radioiodine kinetics, particularly the remnant radiation dose in Gy/GBq of administered (131)I activity (RDpA), could assist in choosing rhTSH-aided ablative activities. MATERIAL AND METHODS: To compare the RDpA, determined through (124)I-positron emission tomography/computed tomography (PET/CT), under the two stimulation methods, we retrospectively divided into two groups 55 consecutive totally-thyroidectomized, radioiodine-naïve patients. The rhTSH group (n=16) received (124)I on thyroid hormone, 24 h after two consecutive daily intramuscular injections of rhTSH, 0.9 mg. The THW group (n=39) received (124)I after weeks-long THW, when serum TSH first measured > or = 25 mIU/L. We performed PET investigations 4 h, 24 h, 48 h, 72 h and 96 h and PET/CT 25 h after (124)I administration. RESULTS: Median stimulated serum thyroglobulin was 15 times higher (p=0.023) and M1 disease almost twice as prevalent (p=0.05) in rhTSH versus THW patients. Mean+/-standard deviation RDpA was statistically equivalent between the groups: rhTSH, 461+/-600 Gy/GBq, THW, 302+/-329 Gy/GBq, two-sided p=0.258. CONCLUSIONS: rhTSH or THW deliver statistically equivalent radiation doses to thyroid remnant and may be chosen based on safety, quality-of-life, convenience and pharmacoeconomic factors. Institutional fixed radioiodine activities formulated for use with THW need not be adjusted for rhTSH-aided ablation.

Value of (124)I-PET/CT in staging of patients with differentiated thyroid cancer.

The aim of this study is to evaluate the clinical significance of (124)I positron emission tomography (PET) using a combined PET/CT tomograph in patients with differentiated thyroid carcinoma and to compare the PET/CT results with (131)I whole-body scintigraphy (WBS), dedicated PET and CT alone. Twelve thyroid cancer patients were referred for diagnostic workup and entered complete clinical evaluation, including histology, cytology, thyroglobulin level, ultrasonography, fluorine-18 fluorodeoxyglucose (FDG)-PET, FDG-PET/CT and CT. Lesion-based evaluation showed a lesion delectability of 56, 87 and 100% for CT, (124)I-PET, and combined (124)I-PET/CT imaging, respectively. Lesion delectability of (131)I-WBS was 83%. We conclude that (124)I-PET/CT imaging is a promising technique to improve treatment planning in thyroid cancer. It is particularly valuable in patients suffering from advanced differentiated thyroid cancer prior to radio-iodine therapy and in patients with suspected recurrence and potential metastatic disease.

Combined PET/CT with iodine-124 in diagnosis of spread metastatic thyroid carcinoma: a case report.

Iodine-124 positron emission tomography (PET) is a useful 3D imaging technique for diagnosis and management of thyroid diseases. The difficulty in interpretation of the PET scans with highly selective tracers, such as iodine-124, is the lack of identifiable anatomical structures, so an accurate anatomical localization of foci presenting abnormal uptake is problematic. Consequently, a combined PET/CT scanner can resolve these difficulties by co-registering PET and CT data in a single session allowing a correlation of functional and morphologic imaging. A case is presented where iodine-124 produced by a clinical cyclotron and FDG were used to acquire images with a combined PET/CT scanner for clinical staging. On the basis of the PET/CT exams the treatment of the patient was modified.

Quantitative kinetics of [124I]FIAU in cat and man.

UNLABELLED: For the assessment of the efficacy of clinical gene therapy trials, different imaging modalities have been developed that enable a noninvasive assessment of location, magnitude, and duration of transduced gene expression in vivo. These imaging methods rely on a combination of an appropriate marker gene and a radiolabeled or paramagnetic marker substrate that can be detected by PET or MRI. Here, we assess whether the nucleoside analog 2'-fluoro-2'-deoxy-1beta-D-arabinofuranosyl-5-iodouracil (FIAU), a specific marker substrate for herpes simplex virus type 1 thymidine kinase (HSV-1-tk) gene expression, penetrates the blood-brain barrier (BBB) as an essential prerequisite for a noninvasive assessment of HSV-1-tk gene expression in gliomas. METHODS: No-carrier-added [(124)I]FIAU was synthesized by reacting the precursor 2'-fluoro-2'-deoxy-1beta-D-arabinofuranosyluracil (FAU) with carrier-free [(124)I]NaI. The course of biodistribution of [(124)I]FIAU was investigated in anesthetized cats (n = 3; organs) and in one patient with a recurrent glioblastoma (plasma and brain) by PET imaging over several hours (cats, 1-22 h) to several days (patient, 1-68 h). FIAU PET was performed in conjunction with multitracer PET imaging (cerebral blood flow and cerebral metabolic rate of O(2) in cats only; cerebral metabolic rate of glucose and [(11)C]methionine in all subjects). A region-of-interest analysis was performed on the basis of coregistered high-resolution MR images. The average radioactivity concentration was determined, decay corrected, and recalculated as percentage injected dose per gram of tissue (%ID/g) or as standardized uptake values (SUVs). RESULTS: The average chemical yield of [(124)I]FIAU synthesis was 54.6% +/- 6.8%. The chemical and radiochemical purities of [(124)I]FIAU were found to be >98% and >95%, respectively. In cats, the kinetic analysis of [(124)I]FIAU-derived radioactivity showed an early peak (1-2 min after injection) in heart and kidneys (0.20 %ID/g; SUV, 4.0) followed by a second peak (10-20 min after injection) in liver and spleen (0.16 %ID/g; SUV, 3.2) with subsequent clearance from tissues and a late peak in the bladder (10-15 h after injection). In the unlesioned cat brain, no substantial [(124)I]FIAU uptake occurred throughout the measurement (<0.02 %ID/g; SUV, <0.4). In the patient, [(124)I]FIAU uptake in normal brain was also very low (<0.0002 %ID/g; SUV, <0.16). In contrast, the recurrent glioblastoma revealed relatively high levels of [(124)I]FIAU-derived radioactivity (5-10 min after injection; 0.001 %ID/g; SUV, 0.8), which cleared slowly over the 68-h imaging period. CONCLUSION: The PET marker substrate FIAU does not penetrate the intact BBB significantly and, hence, is not the marker substrate of choice for the noninvasive localization of HSV-1-tk gene expression in the central nervous system under conditions in which the BBB is likely to be intact. However, substantial levels of [(124)I]FIAU-derived radioactivity may occur within areas of BBB disruption (e.g., glioblastoma), which is an essential prerequisite for imaging clinically relevant levels of HSV-1-tk gene expression in brain tumors after gene therapy by FIAU PET. For this purpose, washout of nonspecific radioactivity should be allowed for several days.

In vitro studies on the cellular uptake of melanoma imaging aminoalkyl-iodobenzamide derivatives (ABA).

The cellular uptake of 11 radioiodinated aminoalkyl-iodobenzamides (ABA) was studied using cultivated murine melanoma cells (B16/C3). All derivatives showed a high uptake (up to about 80%) of radioactivity in melanotic melanoma cells; hence, accumulation of all compounds radioiodinated in the ortho position was reduced by approximately 30%. Using the compound para-[131I]iododiethyl-aminoethylbenzamide (p-131I-ABA-2-2) a close correlation of the cellular melanin content with the tracer uptake (R2 = 0.95) was verified. The presence of extracellular melanin, however, had no effect on the cellular tracer uptake. Because the accumulation was independent of the specific activity of p-131I-ABA-2-2, a significant contribution to the uptake process by binding to receptor sites could be excluded.

123I-MSP and F[11C]MSP: new selective 5-HT2A receptor radiopharmaceuticals for in vivo studies of neuronal 5-HT2 serotonin receptors. Synthesis, in vitro binding study with unlabelled analogues and preliminary in vivo evaluation in mice.

In vitro binding study on bovine brain membranes using [3H]SCH23390, [3H]spiperone, [3H]prazosin and [3H]RP62203 as radioligands (for D1, D2, alpha1 and 5-HT2A receptors respectively) indicate that the new butyrophenones 8-[3-(4-fluorobenzoyl)propyl]-1-methyl-1,3,8-triazaspiro[4,5]de can-4-one (FMSP) and 8-[3-(4-iodobenzoyl)propyl]-1-methyl-1,3,8-triazaspiro[4,5]deca n-4-one (IMSP) exhibit a significantly higher selectivity for the 5-HT2A over D1, D2 and alpha1 receptors. Consequently, the radiolabelled analogues F[11C]MSP and 123I-MSP were prepared in attempt to obtain potential radiopharmaceuticals for in vivo imaging of neuronal 5-HT2A receptors with positron emission tomography (PET) and single photon emission tomography (SPET). F[11C]MSP was synthesized by reaction of [11C]CH3I with 8-[3-(4-fluorobenzoyl)propyl]-1,3,8-triazaspiro[4,5]decan-4- one (DMSP) in 12 +/- 3% radiochemical yield, whereas 123I-MSP was obtained in 82 +/- 8% radiochemical yield by a no-carrier-added Cu(I)-assisted [123I]iododebromination of 8-[3-(4-bromo-benzoyl)propyl]-1-methyl-1,3,8-triazaspiro[4,5]de can-4-ene (BrMSP). In vivo pharmacokinetic and brain binding characterization of 123I-MSP assessed in mice following intravenous injection, showed a fast clearance of 123I-MSP from blood and relatively high initial uptakes in the liver, kidneys and in the lung. Significant uptake and long retention were observed in the brain (up to 1.64% i.d., 60 min p.i.), with a regional accumulation of radioactivity consistent with the reported 5-HT2A receptors distribution in the brain. Frontal cortex to cerebellum ratio of 3.5 was calculated at 60 min p.i. Furthermore, the initial brain uptake was significantly reduced after pretreatment of the animals with ritanserin, a selective 5-HT2 antagonist, and by preinjection of the non-radiolabelled analog IMSP, thus indicating the specificity of the brain uptake. These data suggest that 123I-MSP may be a promising compound for studying the serotoninergic 5-HT2 receptors with SPET. Due to the low specific activity of F[11C]MSP currently obtained by the [11C]methylation reaction, systematic in vivo investigation of F[11C]MSP are as yet not feasable.

Diagnosis of recurrent glioma with SPECT and iodine-123-alpha-methyl tyrosine.

UNLABELLED: Iodine-123-alpha-methyl tyrosine (IMT) allows the investigation of amino acid transport rate in brain neoplasms. It was the aim of this study to evaluate the potential of IMT-SPECT to diagnose the recurrence of gliomas after primary therapy. METHODS: Using a triple-headed SPECT camera, the cerebral uptake of IMT was determined in 27 patients 22 mo, on average, after surgical removal of a primary brain tumor. Eighteen patients had suffered from high-grade gliomas, and nine had suffered from low-grade tumors. Four patients were examined before and after surgical revision of a presumed tumor recurrence. A total of 31 studies were evaluated. The final diagnosis was based on prospective clinicopathological follow-up. Recurrence was diagnosed in 23 cases, with marked clinical deterioration occurring 3.1 mo, on average, after SPECT, and was confirmed by histopathology in 14 instances. Eight cases were free of recurrence, as evidenced by inconspicuous clinical follow-up, ranging from 6 mo to 17 mo after SPECT in seven cases, and by clinical course and histopathology in the remaining subject. RESULTS: Patients with recurrence had significantly higher ratios of IMT uptake in the tumor area to that in a background region than did patients without recurrence (2.27 +/- 0.59 compared to 1.47 +/- 0.29; p < 0.002). The best cutoff level of the IMT uptake ratio in the differentiation between recurrence and benign posttherapeutic lesion was 1.8. Using this study-specific discrimination threshold, the sensitivity and specificity of IMT-SPECT for detecting glioma recurrence were 18 of 23 (78%) and 8 of 8 (100%), respectively. The area under the binormal receiver operating characteristic curve, fitted to the data, was 0.90 +/- 0.06. CONCLUSION: Iodine-123-alpha-methyl tyrosine-SPECT is a promising new tool in the follow-up of patients with gliomas after primary therapy.

Preparation of 8-[3-(4-fluorobenzoyl)-propyl]-1-(4-[123I] iodobenzoyl)-1,3,8-triazaspiro[4,5]decan-4-one: a novel selective serotonin 5-HT2 receptor agent.

In our attempt to develop radioiodinated serotonin 5-HT2 receptor imaging agents for routine clinical application with single photon emission computed tomography (SPECT), the [123I]iodinated compound 8-[3-(4-fluorobenzoyl)-propyl]1-(4-[123I]iodobenzoyl)- 1,3,8-triazaspiro[4,5]decan-4-one [123I]IBSP was prepared via no-carrier-added Cu(I)-assisted radio-iododebromination in acetic acid, followed by purification by means of reversed-phase HPLC in 70-90% radiochemical yield and high specific activities at a total synthesis time of 50 min. Moreover, [123I]-IBSP is stable up to 48 h in aqueous solution at room temperature and revealed appropriate lipophilicity (logP = 2.8) for good diffusion through the blood-brain-barrier. Competitive binding studies on rat brain membranes using [3H]ketanserin, [3H]SCH23390, and [3H]spiperone as radioligands (for 5-HT2, D1 and D2 receptors, respectively) indicated that IBSP has high affinity and selectivity for the serotonin 5-HT2 receptor (Ki = 7.0 nM) over the dopamine D2 (Ki = 153 nM) and D1 receptors (Ki = 265 nM). These data suggest that [123I]-IBSP may be a promising compound for studying 5-HT2 receptors with SPECT.

Non-invasive grading of primary brain tumours: results of a comparative study between SPET with 123I-alpha-methyl tyrosine and PET with 18F-deoxyglucose.

Use of iodine-123-alpha-methyl tyrosine (123I-IMT) allows investigation of the amino acid transport rate in gliomas. It was the aim of this study to compare the value of measurement of glucose metabolism with that of measurement of 123I-IMT uptake for the non-invasive grading of brain tumours. The study population comprised 23 patients with histopathologically proven primary brain tumours; 14 had high-grade gliomas, and nine low-grade brain neoplasms. Glucose metabolism was studied using an ECAT EXACT 47 positron emission tomography (PET) camera and fluorine-18 fluorodeoxyglucose (18F-FDG); 123I-IMT uptake was measured with the triple-headed single-photon emission tomography (SPET) camera, MULTISPECT 3. 18F-FDG and 123I-IMT uptake was quantified as ratios between the uptake by the tumour and contralateral regions of reference. Glucose metabolism and amino acid uptake of the brain tumours correlated significantly (r=0.71, P <0.001). Assuming discrimination thresholds between high-grade and low-grade tumours of 0.8 for 18F-FDG uptake and 1.8 for 123I-IMT uptake, the accuracy values of 18F-FDG PET and 123I-IMT SPET for differentiating between high-grade and low-grade tumours were 21/23 (91%) and 19/23 (83%), respectively. The difference in diagnostic performance was not significant on receiver operating characteristic analysis (P >0.4). It is concluded that there is no major difference between the PET investigation of glucose metabolism and the less expensive SPET measurement of amino acid uptake in terms of their accuracy in evaluating the malignancy grade of primary brain tumours. This encourages the performance of further studies to analyse the potential impact of 123I-IMT SPET on the therapeutic management of patients with brain tumours.

Impact of free prostate-specific antigen on discordant measurement results of assays for total prostate-specific antigen.

OBJECTIVES: To determine why various assays for total PSA (t-PSA) produce discordant results in identical serum samples. METHODS: A total of 84 sera from 40 patients with histologically confirmed benign prostatic hyperplasia and from 44 patients with untreated prostate cancer were analyzed with seven assays for t-PSA and the Hybritech research assay for free prostate-specific antigen (f-PSA). Comparison between assays was performed by linear regression of the t-PSA concentrations as well as between the t-PSA concentrations and the f/t-PSA ratios. RESULTS: The coefficients of correlation for the investigated assays versus Hybritech Tandem-E range from 0.96 to 0.99. Nevertheless average PSA concentrations differed significantly from the Tandem-E assay in all assays. Despite a good correlation, some assays showed a regression line with a slope notably different from 1. In these assays, elevated concentrations were observed in sera with a high proportion of f-PSA. CONCLUSIONS: The study illustrates a significant and clinically relevant discordance between reported t-PSA concentrations for identical samples, depending on the assay used and on the contents of f-PSA in the sample. The interpretation of t-PSA concentrations requires awareness of the applied assay as well as the establishment of an assay-specific reference range in order to avoid inappropriate clinical consequences, such as unnecessary biopsies. Respective details must be contained in the laboratory reports. A change of assays without specifically reassessing previously valid reference ranges or the uncritical use of a customarily applied limit of < 4 ng/mL will otherwise be harmful to the patient.

Simultaneous evaluation of fatty acid metabolism and myocardial flow in an explanted heart.

UNLABELLED: The biodistribution of the fatty acid analog [131I]PHIPA 3-10, was compared to the flow tracer 99mTc-sestamibi by quantitative analysis in a dual-isotope study performed during a heart transplantation. METHODS: Iodine-131-PHIPA 3-10 and 99mTc-sestamibi were injected simultaneously approximately 20 min prior to the start of surgical procedure. Scintigraphic images of the sliced explanted heart were compared to the preoperative in vivo scans using [123I]PHIPA 3-10, 201TI and 99mTc-sestamibi. In 14 tissue samples of the explanted heart, the radioactive contents from [131I]PHIPA 3-10 and 99mTc-sestamibi were calculated as %ID/g-values and correlated with the corresponding histology. RESULTS: In the preoperative scans, a mismatch of fatty acid uptake and perfusion ([123I]PHIPA 3-10 > flow) was observed which indicated residual viable myocardium, while a matched defect was associated with scar. In viable myocardium, there was a significantly higher accumulation of [131I]PHIPA 3-10 compared to 99mTc-sestamibi (mean 5.9 x 10(-3) versus 2.7 x 10(-3)%ID/g),whereas in scars the uptake of both tracers was comparable (1.2 x 10(-3) versus 1.4 x 10(-3)%ID/g). CONCLUSION: Myocardial viability can be defined more accurately with radioiodinated PHIPA 3-10 than with 99mTc-sestamibi. The differences of biodistribution in viable myocardium and scars indicate that not only perfusion but also the metabolic state of the myocardium can be evaluated with radioiodinated PHIPA 3-10.

Structure distribution relationship of iodine-123-iodobenzamides as tracers for the detection of melanotic melanoma.

UNLABELLED: The influence of systematic structure variations on the biodistribution of positional isomers of N-(N'-dialkylaminoethylene)-[123I]iodobenzamide (ABA) derivatives in melanoma-bearing animals was investigated. METHODS: Radioiodination of six bromo benzamide precursors was achieved by Cu(1)-assisted nonisotopic halogen exchange. Organ distribution, scintigraphic and metabolic studies were performed in nude mice bearing a human melanotic MM (SK-MEL 25). A patient suffering from melanotic melanoma underwent scintigraphy with a [123I]iodobenzamide. RESULTS: High radiochemical yields of 80%-95% and specific activities of > 5 TBq/ mumole were obtained. Animal studies revealed specific tumor uptake of all compounds with longest retention of the most lipophilic derivative p-[123I]ABA 2-2. At shorter times, however, o-[123I]ABA 2-2 exhibited the highest tumor uptake (8.9% ID/g, 1 hr p.i., 10.9% ID/g, 4 hr p.i.). Metabolization of o-[123I]ABA 2-2, mainly to o-[123I]iodohippuric acid (OIH), followed by fast renal excretion of the metabolites lead to tumor/nontumor ratios (T/NT) of > 400 for tumor/blood, and > 70 for tumor/liver at 48 h p.i. Unknown metastases could be localized in a patient using o-[123I]ABA 2-2. CONCLUSION: The effects of the structure variation of iodobenzamides on their lipophilicity, metabolism and thus pharmacokinetics lead to the suggestion of o-[123I]ABA 2-2 as a favorable melanoma imaging agent.

Synthesis, characterization and biodistribution of neutral and lipid-soluble 99mTc-bisaminoethanethiol spiperone derivatives: possible ligands for receptor imaging with SPECT.

Using parts of the molecular structure of spiperone, two new ligand systems for complexation with [99mTc]technetium were prepared in order to develop potential receptor imaging agents for single photon emission computer tomography (SPECT). The bis-aminoethanethiols (BAT): 1-benzyl-4-(2-mercapto-2-methyl-4-aza-pentyl)-4-(2-mercapto-2-methyl- propylamino)-piperidine (benzylpiperidyl-BAT, BP-BAT) and 1-[3-(4-fluorobenzoyl)-propyl]-4-(2-mercapto-2-methyl-4-aza-pentyl)-4- (2-mercapto-2-methyl-propyl-amino)-piperidine (butyrophenoylpiperidyl-BAT, BUP-BAT) form stable, neutral and lipid soluble complexes with [99mTc]technetium at pH > or = 11 using SnCl2 as reducing agent in nearly quantitative radiochemical yields. Biodistribution of 99mTc-BP-BAT and 99mTc-BUP-BAT in rats showed a moderate clearance from blood and low uptake and retention in the liver, whereas brain uptake was moderate, however with prolonged brain retention. On the other hand, significant accumulations and retentions were observed in heart, kidney and lung with increasing oxygen/blood ratios up to 24 h. Within 24 h p.i. 22 and 29% of the injected dose (i.d.) of 99mTc-BP-BAT and 99mTc-BUP-BAT were eliminated by hepatobiliary excretion whereas 22% i.d. of both 99mTc-BAT complexes were excreted into the urine. Although first biodistribution studies of 99mTc-BP-BAT and 99mTc-BUP-BAT in rats showed relatively low brain uptake, the high uptake in peripheral, receptor rich organs indicates that compounds of this type may be used as a basis for further structural modification to develop agents with optimal properties for cerebral or peripheral receptor imaging with SPECT.

New renal function imaging agents. I. Synthesis and biological characterization of a [99mTc]diaminomercapto(thio)ether (DAMTE).

The present study describes the synthesis of a [99mTc]diaminomercapto(thio)ether (DAMTE-derivative) as a first compound of a new class of 99mTc-complexes which is tubular excreted. 10-Benzoyl-8-keto-7-aza-2-amino-4,10-dithia-decanoic acid (CO2-DAMTE 3) was synthesized by the reaction of succinimidyl-S-benzoyl-thioglycolate and (S)-2-aminoethyl-L-cysteine. The respective technetium complex, 99mTc-CO2-DAMTE was obtained in radiochemical yields of about 70% using stannous chloride as reducing agent. Hydrolysis of the protecting group was performed either prior to the complexation of pertechnetate ("cold kit") or during the labelling reaction ("hot kit"). Organ distribution was determined in Wistar rats. Within 24 h 40% of the activity were excreted into the feces and 43% into the urine, whereas 10% were retained in the kidneys. In contrast, a first human study showed a very fast renal elimination of 99mTc-CO2-DAMTE, a low liver uptake (< 10%) and no retention in the kidneys. The renal clearance of approx. 240 mL/min/1.73 m2 in addition to the protein binding of > 95% suggests an effective tubular excretion of the compound.

[Guidelines for radiation protection in medicine--radiopharmaceutical quality control. German Society of Nuclear Medicine]. / Richtlinie Strahlenschutz in der Medizin--Radiopharmazeutische Qualitätskontrolle.

For the first time the revision of the "Guideline for radiation protection in medicine" defines extensive quality control procedures for radiopharmaceuticals. The principles of the 99Mo/99mTc-generator, the preparation of 99mTc-radiopharmaceuticals and the origin of the most frequent radiochemical impurities are illustrated. An introduction into the theory of thin layer chromatography is combined with a listing of radiochromatographic systems. This enables the determination of the radiochemical purity of the most important radiopharmaceuticals in clinical routine.

N-(2-diethylaminoethyl)-4-[123I]iodobenzamide as a tracer for the detection of malignant melanoma: simple synthesis, improved labelling technique and first clinical results.

In order to evaluate the behaviour of N-(2-diethylaminoethyl)-4-[123I]iodobenzamide in malignant melanotic disease, we synthesized the bromo compound in a simple one-step reaction. Labelling was performed by non-isotopic bromine-iodine-123 exchange in radiochemical yields up to 60%. By means of isocratic high-performance liquid chromatography, the iodinated product could be isolated with high apparent specific activity. First clinical studies in patients with malignant melanoma using N-(2-diethylaminoethyl)-4-[123I]iodobenzamide showed moderate uptake of the tracer in the tumour and the suspected metastases in all patients. Most of the lesions were detectable with technetium-99m-diethylene triamine penta-acetic acid (DTPA) scintigraphy too, but we were able to detect additional, previously unidentified metastases with benzamide scintigraphy. This changed the therapeutic procedure in two of the five cases investigated so far.

Determination of cerebral perfusion by means of planar brain scintigraphy and 99mTc-HMPAO in brain death, persistent vegetative state and severe coma.

A total of 24 patients with clinical evidence of brain death (n = 17), severe coma (n = 2; GCS approximately 3) and apallic syndrome (n = 4) underwent a comparative investigation with 99mTc-HMPAO brain scintigraphy, EEG, auditory and somatosensory evoked potentials. Accompanied by EEG and evoked potentials, brain scintigraphy enabled confirmation of cerebral death in 15/17 patients. In one case clinical examination and evoked potentials suggest brain death, but cerebral perfusion and EEG were normal ("brain stem death"). One patient with evidence of cerebral death in clinical examination, brain scintigraphy and evoked potentials, showed questionable focal EEG activity; however, autopsy revealed intravital autolysis of the entire brain. All patients with apallic syndrome and deep coma showed a distinct cerebral perfusion, but gross EEG abnormalities; evoked potentials were delayed or absent. Planar scintigraphy with 99mTc-HMPAO appears to be superior to neurophysiological techniques discriminating patients with agonal cerebral dysfunction from those with brain death.

Comparison of technetium 99m polyclonal human immunoglobulin and technetium 99m monoclonal antibodies for imaging chronic osteomyelitis. First clinical results.

The accuracy of technetium-99m human immunoglobulin (HIG) for the detection of chronic osteomyelitis (OM) was compared with white blood cell scintigraphy using 99mTc-labelled monoclonal mouse antibodies (MAB). Seventeen patients suspected of having OM in 20 lesions went through three-phase skeletal scintigraphy, HIG scintigraphy and MAB scintigraphy. The final diagnosis was established by open surgery, histology and bacteriology. Chronic OM was proved in 14/20 lesions. Six of these 14 infections were located in peripheral areas without active bone marrow and 8/14 in central areas with active bone marrow. In peripheral OM, 5/6 with HIG and 6/6 with MAB were true positives. In the central skeleton all 8/8 infections appeared as cold lesions in the MAB study, which were defined as being false negative due to their non-specificity. Using HIG, 5/8 central infections were determined to be truly positive by showing photon-rich lesions. These 5 lesions were located in the hip region and in the pelvis, whereas 3 lesions of the spine were missed. There were no false-positive results in either studies. In conclusion, MAB was superior to HIG in peripheral OM concerning sensitivity, anatomical landmarks and differentiation of soft tissue versus bone infection. In central OM MAB detected all lesions accurately, but no differential diagnosis was possible due to the non-specificity of photon-low areas. In this respect HIG seems to be more specific due to the increased accumulation even in central infection sites.