Novel ion exchange chromatography method for nca arsenic separation.

A high-performance liquid chromatography (HPLC) device equipped with an anion exchange column was used to isolate nca 77As from reactor irradiated natGeO2 targets. The oxidation states of the isotope 77As during the process was verified by thin layer chromatography. The radionuclidic purity of the separated fractions was checked by gamma measurements and it was found to be 99.91% for the As fraction. The elaborated method was applied to separate the isotope 74As from cyclotron irradiated natGeO2 targets too.

In vivo analysis of neuroinflammation in the late chronic phase after experimental stroke.

BACKGROUND AND PURPOSE: In vivo imaging of inflammatory processes is a valuable tool in stroke research. We here investigated the combination of two imaging modalities in the chronic phase after cerebral ischemia: magnetic resonance imaging (MRI) using intravenously applied ultra small supraparamagnetic iron oxide particles (USPIO), and positron emission tomography (PET) with the tracer [(11)C]PK11195. METHODS: Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) by the macrosphere model and monitored by MRI and PET for 28 or 56 days, followed by immunohistochemical endpoint analysis. To our knowledge, this is the first study providing USPIO-MRI data in the chronic phase up to 8 weeks after stroke. RESULTS: Phagocytes with internalized USPIOs induced MRI-T2(∗) signal alterations in the brain. Combined analysis with [(11)C]PK11195-PET allowed quantification of phagocytic activity and other neuroinflammatory processes. From 4 weeks after induction of ischemia, inflammation was dominated by phagocytes. Immunohistochemistry revealed colocalization of Iba1+ microglia with [(11)C]PK11195 and ED1/CD68 with USPIOs. USPIO-related iron was distinguished from alternatively deposited iron by assessing MRI before and after USPIO application. Tissue affected by non-phagocytic inflammation during the first week mostly remained in a viably vital but remodeled state after 4 or 8 weeks, while phagocytic activity was associated with severe injury and necrosis accordingly. CONCLUSIONS: We conclude that the combined approach of USPIO-MRI and [(11)C]PK11195-PET allows to observe post-stroke inflammatory processes in the living animal in an intraindividual and longitudinal fashion, predicting long-term tissue fate. The non-invasive imaging methods do not affect the immune system and have been applied to human subjects before. Translation into clinical applications is therefore feasible.

Neither azeotropic drying, nor base nor other additives: a minimalist approach to (18)F-labeling.

A novel, efficient, time-saving and reliable radiolabeling procedure via nucleophilic substitution with [(18)F]fluoride is described. Different radiolabeled aliphatic and aromatic compounds were prepared in high radiochemical yields simply by heating of quaternary anilinium, diaryliodonium and triarylsulfonium [(18)F]fluorides in suitable solvents. The latter were obtained via direct elution of (18)F(-) from an anion exchange resin with alcoholic solutions of onium precursors. Neither azeotropic evaporation of water, nor a base, nor any other additives like cryptands or crown ethers were necessary. Due to its simplicity this method should be highly suitable for automated radiosyntheses, especially in microfluidic devices.

Effects of minocycline on endogenous neural stem cells after experimental stroke.

Minocycline has been reported to reduce infarct size after focal cerebral ischemia, due to an attenuation of microglia activation and prevention of secondary damage from stroke-induced neuroinflammation. We here investigated the effects of minocycline on endogenous neural stem cells (NSCs) in vitro and in a rat stroke model. Primary cultures of fetal rat NSCs were exposed to minocycline to characterize its effects on cell survival and proliferation. To assess these effects in vivo, permanent cerebral ischemia was induced in adult rats, treated systemically with minocycline or placebo. Imaging 7 days after ischemia comprised (i) Magnetic Resonance Imaging (MRI), assessing the extent of infarcts, (ii) Positron Emission Tomography (PET) with [(11)C]PK11195, characterizing neuroinflammation, and (iii) PET with 3'-deoxy-3'-[(18)F]fluoro-L-thymidine ([(18)F]FLT), detecting proliferating endogenous NSCs. Immunohistochemistry was used to verify ischemic damage and characterize cellular inflammatory and repair processes in more detail. In vitro, specific concentrations of minocycline significantly increased NSC numbers without increasing their proliferation, indicating a positive effect of minocycline on NSC survival. In vivo, endogenous NSC activation in the subventricular zone (SVZ) measured by [(18)F]FLT PET correlated well with infarct volumes. Similar to in vitro findings, minocycline led to a specific increase in endogenous NSC activity in both the SVZ as well as the hippocampus. [(11)C]PK11195 PET detected neuroinflammation in the infarct core as well as in peri-infarct regions, with both its extent and location independent of the infarct size. The data did not reveal an effect of minocycline on stroke-induced neuroinflammation. We show that multimodal PET imaging can be used to characterize and quantify complex cellular processes occurring after stroke, as well as their modulation by therapeutic agents. We found minocycline, previously implied in attenuating microglial activation, to have positive effects on endogenous NSC survival. These findings hold promise for the development of novel treatments in stroke therapy.

Progression of subtle motor signs in PINK1 mutation carriers with mild dopaminergic deficit.

BACKGROUND: While homozygous mutations in the PINK1 gene cause recessively inherited early-onset Parkinson disease (PD), heterozygous mutations have been suggested as a susceptibility factor. METHODS: To evaluate this hypothesis, 4 homozygous PINK1 patients with PD and 10 asymptomatic carriers of a single heterozygous mutation from a large German family (family W) were included in this study. Clinical follow-up of the heterozygous mutation carriers 3 years after the initial visit included a detailed videotaped neurologic examination using the Unified Parkinson's Disease Rating Scale III protocol and smell and color discrimination testing. At follow-up, PET with 18-fluorodopa (FDOPA) of 13 family members was obtained in order to evaluate the clinical phenotype in light of nigostriatal dopaminergic functioning. The clinical and PET data were compared to those of healthy controls. RESULTS: While there was mild worsening of clinical signs in previously affected heterozygous mutation carriers upon follow-up, 3 additional individuals had newly developed signs of possible PD. Hyposmia was found in 7 of the heterozygous mutation carriers, diminished color discrimination in 4. The homozygous mutation carriers who were all definitely affected with PD showed a severe, 60% decrease of caudate and putaminal FDOPA uptake; heterozygous offspring also had a significant 20% putaminal FDOPA uptake reduction compared to controls. CONCLUSIONS: Our findings strengthen the hypothesis that heterozygous PINK1 mutations act as a susceptibility factor to develop at least subtle Parkinson disease motor and nonmotor signs, as supported by the finding of a reduced striatal dopaminergic FDOPA uptake not only in homozygous but also, albeit to a lesser extent, in heterozygous mutation carriers.

Synthesis and evaluation of 18F-fluoroethylated benzothiazole derivatives for in vivo imaging of amyloid plaques in Alzheimer's disease.

Amyloid aggregates play a major role in the development of Alzheimer's disease. Targeting these aggregates by PET probes enables non-invasively the detection and quantification of amyloid deposit distribution in human brains. Based on benzothiazole core structure a series of amyloid imaging agents were developed. Currently [(11)C]2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole (Pittsburgh Compound-B (PIB) is the most specific and widely used amyloid imaging ligand. But due to the short half life of (11)C, longer lived (18)F-labeled derivatives offer logistic advantages and higher contrast images. In this work, three different [(18)F]fluoroethoxy-substituted benzothiazole derivatives ([(18)F]2-(4'-(methylamino)phenyl)-6-(2-fluoroethoxy)benzothiazole, [(18)F]2-((2'-(2-fluoroethoxy)-4'-amino)phenyl)benzothiazole and [(18)F]2-(3'-((2-fluoroethoxy)-4'-amino)phenyl)benzothiazole) were synthesized via [(18)F]fluoroethylation. The latter two derivatives with fluoroethoxy-substitution on the aromatic amino group showed very low binding affinity for amyloid aggregates. In contrast [(18)F]2-(4'-(methylamino)phenyl)-6-(2-fluoroethoxy)benzothiazole with [(18)F]fluoroethoxy-substitution in 6-position showed excellent amyloid imaging properties with respect to lipophilicity, brain entry and brain clearance in normal SCID mice, amyloid plaque binding affinity and specificity.

A fully automated two-step synthesis of an (18)F-labelled tyrosine kinase inhibitor for EGFR kinase activity imaging in tumors.

Radiolabelled epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitors potentially facilitate the assessment of EGFR overexpression in tumors. Since elaborate multi-step radiosyntheses are required for (18)F-labelling of EGFR-specific anilinoquinazolines we report on the development of a two-step click labelling approach that was adapted to a fully automated synthesis module. 6-(4-N,N-Dimethylaminocrotonyl)amido-4-(3-chloro-4-fluoro)phenylamino-7-{3-[4-(2-[(18)F]fluoroethyl)-2,3,4-triazol-1-yl]propoxy}quinazoline ([(18)F]6) was synthesized via Huisgen 1,3-dipolar cycloaddition between 2-[(18)F]fluoroethylazide ([(18)F]4) and the alkyne modified anilinoquinazoline precursor 5. PET images of PC9 tumor xenograft using the novel biomarker showed promising results to visualize EGFR overexpression.

Radiosynthesis and evaluation of [11C]BTA-1 and [11C]3'-Me-BTA-1 as potential radiotracers for in vivo imaging of beta-amyloid plaques.

AIM: To evaluate the in vitro and in vivo characteristics of [N-methyl-(11)C]2-(4'-(methylaminophenyl)-benzothiazole ([(11)C]BTA-1) as well as [N-methyl-(11)C]2-(3'-methyl-4'-(methylamino)phenyl)-benzothiazole ([(11)C]3'-Me-BTA-1) as diagnostic markers of amyloid-beta (Abeta) in Alzheimer's disease (AD). MATERIAL, METHODS: Brain uptake and clearance was determined in wild-type mice. Binding affinities (K(i)) of [(11)C]BTA-1 and [(11)C]3'-Me-BTA-1 for aggregated Abeta(1-40) fibrils were assessed. Autoradiography was performed on brain sections of AD patients. To demonstrate binding specificity in vivo BTA-1 was injected i.p. in transgenic mice (Tg2576). Brain sections were analysed consecutively. Additionally, a [(11)C]BTA-1 PET study of an AD patient and a healthy control was performed. RESULTS: In mice brain uptake and clearance of [(11)C]BTA-1 is compatible with the half life of (11)C (2 min: 12.7 % ID/g; 30 min: 4.6% ID/g). In contrast clearance rate of [(11)C]3'-Me-BTA-1 is too slow (2 min 4% ID/g; 30 min 12% ID/g) to achieve sufficient clearance of free and non specifically bound radioactivity. K(i) of [(11)C]BTA-1 is 11 nmol/l and that of [(11)C]3'-Me-BTA-1 27 nmol/l. Both radioligands label Abeta selectively and specifically in AD patients and transgenic mice in vitro. The in vivo stained brain sections show a labelling of Abeta plaques. The AD patient has a higher prefrontal, parietal and striatal [(11)C]BTA-1 accumulation than the healthy control. Metabolite analysis revealed approximately 75% intact [(11)C]BTA-1 after 30min in plasma.[(11)C]BTA-1 is favourable for in vivo imaging of Abeta due to its rapid brain entry, sufficient clearance and good binding affinity for Abeta. CONCLUSION: The ability to label Abeta plaques in vivo in human subjects supports the suitability of [(11)C]BTA-1 as a plaque imaging agent.

Radiation dosimetry and biodistribution of the beta-amyloid plaque imaging tracer 11C-BTA-1 in humans.

AIM: [N-methyl-(11)C]2-(4'-(methylaminophenyl)-benzothiazole ((11)C-BTA-1) is a thioflavin-T derivative that has been one of the promising PET tracers for imaging of amyloid plaque distribution in the Alzheimer patients brain in vivo. The biodistribution and dosimetry of this tracer in humans is presented and compared to the results of a previous dosimetry and biodistribution study of another thioflavin-T derivative [N-methyl-(11)C]2-hydroxy-(4'-(methylaminophenyl)-benzothiazole ((11)C-OH-BTA-1) in baboons. METHODS: Five subjects underwent 2D dynamic PET imaging. Source organs were segmented using a semiautomatic algorithm based on clustering. Residence times for each source organ were determined by analytical integration of an exponential fit of the time activity curves. Finally organ doses were estimated using the software OLINDA/EXM. RESULTS: The administration of 286 +/- 93 MBq (11)C-BTA-1 was well tolerated by all subjects. Effective radiation dose was 4.3 microSv/MBq, range 3.6-5.0 microSv/MBq. In four of the five subjects the liver, in one of the subjects the gallbladder was the critical organ. CONCLUSION: The radiation burden of a single dose of 300 MBq (11)C-BTA-1 is within the accepted limits for research purpose. In contrast to the previous non-human primate study revealing the gallbladder as the critical organ for (11)C-6-OH-BTA-1, we found the liver as the critical organ in humans using (11)C-BTA-1. Possible explanations may be (1) a reduced bile concentration of (11)C-BTA-1 due to the absent OH-group or (2) a different hepatic metabolism of thioflavin derivatives in human and baboon.

Dosimetry with (188)Re-labelled monoclonal anti-CD66 antibodies. A simplified approach based on a single measurement 3 h p.i.

AIM: For the therapeutic application of radiopharmaceuticals the activity is determined on an individual basis. Here we investigated the accuracy for a simplified assessment of the residence times for a (188)Re-labelled anti-CD66 monoclonal antibody. PATIENTS, METHODS: For 49 patients with high risk leukaemia (24 men, 25 women, age: 44 +/- 12 years) the residence times were determined for the injected (188)Re-labelled anti-CD66 antibodies (1.3 +/- 0.4 GBq, 5-7 GBq/mg protein, >95% (188)Re bound to the antibody) based on 5 measurements (1.5, 3, 20, 26, and 44 h p.i.) using planar conjugate view gamma camera images (complete method). In a simplified method the residence times were calculated based on a single measurement 3 h p.i. RESULTS: The residence times for kidneys, liver, red bone marrow, spleen and remainder of body for the complete method were 0.4 +/- 0.2 h, 1.9 +/- 0.8 h, 7.8 +/- 2.1 h, 0.6 +/- 0.3 h and 8.6 +/- 2.1 h, respectively. For all organs a linear correlation exists between the residence times of the complete method and the simplified method with the slopes (correlation coefficients R > 0.89) of 0.89, 0.99, 1.23, 1.13 and 1.09 for kidneys, liver, red bone marrow, spleen and remainder of body, respectively. CONCLUSION: The proposed approach allows reliable prediction of biokinetics of (188)Re-labelled anti-CD66 monoclonal antibody biodistribution with a single study. Efficient pretherapeutic estimation of organ absorbed dose may be possible, provided that a more stable anti-CD66 antibody preparation is available.

Lymph node staging in lung cancer using [18F]FDG-PET.

BACKGROUND: Mediastinal lymph node staging is essential to determine treatment options in patients with NSCLC. Positron emission tomography (PET) detects increased glucose uptake in malignant tissue using the glucose analogue 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG). PATIENTS AND METHODS: In the present study were evaluated 155 patients with focal pulmonary tumors who underwent both preoperative computed tomography (CT) and FDG-PET scanning (116 malignant and 39 benign lesions). RESULTS: Findings in 155 patients included 116 malignant and 39 benign lesions. For N-staging, FDG-PET showed a sensitivity of 88%, a specificity of 91%, and an accuracy of 89%. Corresponding figures for CT were 77%, 76%, and 77%, respectively. CONCLUSIONS: FDG-PET is an effective, noninvasive method for staging thoracic lymph nodes in patients with lung cancer and is superior to CT scanning in the assessment of hilar and mediastinal nodal metastases. With regard to operability, FDG-PET could differentiate reliable between patients with N1/N2 disease and those with unresectable N3 disease.

[18F] 3-deoxy-3'-fluorothymidine positron emission tomography: alternative or diagnostic adjunct to 2-[18f]-fluoro-2-deoxy-D-glucose positron emission tomography in the workup of suspicious central focal lesions?

BACKGROUND: 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography has been established as a standard diagnostic imaging method in the preoperative workup of suspicious pulmonary focal lesions, showing a sensitivity of more than 90% and a specificity of about 80%. Determination of malignant pulmonary lesions with FDG positron emission tomography depends on the assessment of glucose metabolism. However, false-positive findings can occur in inflammatory processes, such as sarcoidosis or pneumonia. The thymidine analogue 3-deoxy-3[(18)F]-fluorothymidine (FLT) is a new positron emission tomography tracer that more specifically targets proliferative activity of malignant lesions. The objective of this study was to determine whether FLT positron emission tomography, in comparison with FDG positron emission tomography, provides additional information in the preoperative workup of central pulmonary focal lesions. METHODS: In this prospective study FLT and FDG positron emission tomography examinations were performed as a part of the preoperative workup in 20 patients with histologically confirmed bronchial carcinoma, 7 patients with benign lesions, and 1 patient with an atypical carcinoid. Results were compared with final pathologic findings. RESULTS: For staging of the primary tumor, FLT positron emission tomography revealed a sensitivity of 86% and a specificity of 100% compared with a sensitivity of 95% and a specificity of 73% for FDG positron emission tomography. For N staging, the sensitivity of FLT positron emission tomography was 57% and the specificity was 100%, and for FDG positron emission tomography, the sensitivity was 86% and the specificity was 100%, respectively. CONCLUSIONS: Our preliminary findings indicate specific FLT uptake in malignant lesions. The number of false-positive findings in FDG positron emission tomography might be reduced with FLT positron emission tomography. Therefore positron emission tomography imaging with FLT represents a useful supplement to FDG in assessing the malignancy of central pulmonary focal lesions.

Intraindividual comparison of [11C]acetate and [11C]choline PET for detection of metastases of prostate cancer.

UNLABELLED: In a pilot trial we investigated whether significant differences in prostate cancer (PCA) imaging would be observed using [(11)C]acetate and [(11)C]choline positron emission tomography (PET). METHODS: Twelve patients were studied with both radiotracers. Whole body PET without attenuation correction was performed after injection of 0.95 +/- 0.15 GBq [(11)C]acetate and 0.84 +/- 0.13 GBq [(11)C]choline, respectively, from 5 to 60 min p. i. Focally increased uptake in bone, below the urinary bladder or in a lymph node region was considered as tumour. Primary tumour, lymph node involvement, bone metastases, local recurrence; and no evidence of disease were known in 2, 4, 2, 2; and 2 patients, respectively. RESULTS: [(11)C]Acetate uptake was highest in spleen and pancreas while [(11)C]choline uptake was predominant in liver and kidney parenchyma. However, interindividual variation was high. The potential of both radiotracers to detect known bone lesions, lymph node metastases, and imaging of the primary tumour was identical. However, both failed to detect a small local recurrence in two patients as well as to demonstrate lymph node involvement in one patient, which was confirmed by surgery. CONCLUSIONS: In this preliminary study, uptake of both radiotracers in prostate cancer or its metastases was nearly identical and none of them should be favoured. At present, both radiotracers influence patient management by detection of local recurrence, lymph node, or bone metastases of PCA.

Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation.

Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates (188Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2+/-2.1 (range 6.9-15.8) GBq 188Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4+/-5.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking 188Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia.

In vivo evaluation of 5-[(18)F]fluoro-2'-deoxyuridine as tracer for positron emission tomography in a murine pancreatic cancer model.

We used a murine tumor progression model for the evaluation of potential proliferation markers using positron emission tomography (PET). 5-[(18)F]-2'-deoxyuridine ([(18)F]FdUrd) was synthesized with >98% radiochemical purity and investigated in a pancreatic cancer model, transforming growth factor alpha transgenic mice crossbred to p53 deficient mice. Thymidylate synthase was increased already in premalignant lesions, whereas thymidine kinase 1 mRNA levels were up-regulated 4-fold in the pancreatic cancer specimen of these mice. PET imaging was performed after injection of 1 MBq of [(18)F]FdUrd and 1 MBq of [(18)F]fluoro-deoxyglucose. Animals with pancreatic cancer displayed focal uptake of both tracers. The [(18)F]FdUrd uptake ratio closely correlated with the proliferation index as evaluated in morphometric and fluorescence-activated cell sorter analysis. These results indicate the potential of our tumor model for the evaluation of PET tracers and suggest [(18)F]FdUrd as a tracer for the assessment of proliferation in vivo.

Validation of myocardial blood flow estimation with nitrogen-13 ammonia PET by the argon inert gas technique in humans.

We simultaneously determined global myocardial blood flow (MBF) by the argon inert gas technique and by nitrogen-13 ammonia positron emission tomography (PET) to validate PET-derived MBF values in humans. A total of 19 patients were investigated at rest (n = 19) and during adenosine-induced hyperaemia (n = 16). Regional coronary artery stenoses were ruled out by angiography. The argon inert gas method uses the difference of arterial and coronary sinus argon concentrations during inhalation of a mixture of 75% argon and 25% oxygen to estimate global MBF. It can be considered as valid as the microspheres technique, which, however, cannot be applied in humans. Dynamic PET was performed after injection of 0.8 +/- 0.2 GBq 13N-ammonia and MBF was calculated applying a two-tissue compartment model. MBF values derived from the argon method at rest and during the hyperaemic state were 1.03 +/- 0.24 ml min-1 g-1 and 2.64 +/- 1.02 ml min-1 g-1, respectively. MBF values derived from ammonia PET at rest and during hyperaemia were 0.95 +/- 0.23 ml min-1 g-1 and 2.44 +/- 0.81 ml min-1 g-1, respectively. The correlation between the two methods was close (y = 0.92x + 0.14, r = 0.96; P < 0.0001). No indication was found for limited extraction of ammonia in the myocardium. The high concordance of global MBF values derived with argon and ammonia indicates that the implicit correction of spillover and recovery effects, incorporated in the model by including an effective blood volume parameter, works correctly quantitatively. Our data provide the previously missing human validation of MBF measurements from 13N-ammonia PET.

In vivo imaging of activated microglia using [11C]PK11195 and positron emission tomography in patients after ischemic stroke.

Neuroprotective strategies are currently being developed for stroke patients. Although the focus is on the development of early treatment the importance of late pathogenetic events is increasingly recognized. To investigate the microglial reaction in stroke we used a marker for activated microglia, [11C]PK11195, and PET in five patients with ischemic stroke 5-53 days after infarction. In one patient serial measurements were made. We demonstrated in each individual and at each point in time that a microglial reaction takes place in the area where T1 weighted MRI (magnetic resonance imaging) shows intensity changes. We consider this PET method as a promising tool to study the late pathogenetic consequences of cerebral infarction and to evaluate neuroprotective strategies with respect to the consequences of the microglial activation.

Experience with carbon-11 choline positron emission tomography in prostate carcinoma.

We investigated the potential of carbon-11 choline positron emission tomography (PET) for the detection of lymph node and bone metastases in prostate cancer. A total of 23 patients were studied (known metastases: 8; suspicion of metastases: 3; primary staging: 12). Whole-body PET imaging was performed 5 min after injection of the tracer and completed within 1 h. Focally increased tracer uptake in bone or abdominal lymph node regions was interpreted as representing tumour involvement. All known bone and lymph node metastases could be recognized by [11C]choline PET. One out of ten negative scans for primary staging was false-negative (lymph node <1 cm) and one out of two positive scans was false-positive with regard to lymph node involvement (focal bowel activity). It is concluded that [11C]choline PET is a promising new tool for the primary staging of prostate cancer, with lymph node and bone metastases demonstrating high tracer uptake. Therapeutic management could be influenced by these results in that the technique may permit avoidance of surgical lymph node exploration.

Radioimmunotherapy for the intensification of conditioning before stem cell transplantation: differences in dosimetry and biokinetics of 188Re- and 99mTc-labeled anti-NCA-95 MAbs.

UNLABELLED: A new concept is the intensification of preparative regimens for patients with advanced leukemia using monoclonal antibodies (MAbs) with an affinity for beta emitter-labeled bone marrow. 188Re is a high-energy beta emitter that has therapeutic promise. Our first aim was to clarify whether the therapeutic application of 188Re-MAb against nonspecific cross-reacting antigen 95 (NCA-95) can be predicted from biokinetic data derived from 99mTc-labeled NCA-95. Our second aim was to show that a radiation absorbed dose of > or =12 Gy in the bone marrow can be achieved using 188Re-MAb. METHODS: Dosimetric data were obtained for both radiotracers from multiple planar whole-body scans (double-head gamma camera), blood samples, and urine measurements from 12 patients with advanced leukemia. Radiation absorbed doses were calculated using MIRDOSE 3 software. RESULTS: Radiation absorbed doses to bone marrow, liver, spleen, lung, and kidney were 2.24, 0.50, 1.93, 0.05, and 0.90 mGy/MBq, respectively, using 99mTc-MAb and 1.45, 0.43, 1.32, 0.07, and 0.71 mGy/MBq, respectively, using 188Re-MAb. These differences were statistically significant for bone marrow, spleen, and kidney. The main differences were less accumulation of 188Re-MAb in bone marrow (31%+/-13% compared with 52%+/-13%) and faster elimination through urine (25%+/-3% compared with 15%+/-5% after 24 h). On the basis of these data, a mean marrow dose of 14+/-7 Gy was achieved in 12 patients suffering from leukemia after application of approximately 10+/-2 GBq 188Re-MAb. CONCLUSION: Myeloablative radiation absorbed doses can easily be achieved using 188Re-MAb. 99mTc- and 188Re-MAb showed similar whole-body distributions. However, direct prediction of radiation absorbed doses from the 99mTc-MAb, assuming identical biokinetic behavior, is not valid for the 188Re-MAb in a single patient. Therefore, individual dosimetry using 188Re-MAb is needed to calculate therapeutic activity.