[99cmTc]Tc-PSMA-I&S-SPECT/CT: experience in prostate cancer imaging in an outpatient center.

BACKGROUND: Prostate-specific membrane antigen (PSMA) SPECT imaging in prostate cancer (PCa) could be a valuable alternative in regions where access to PSMA-PET imaging is restricted. [99mTc]Tc-PSMA-I&S is a new 99mTc-labeled PSMA-targeting SPECT agent, initially developed for radio-guided surgery. We report on the diagnostic use of [99mTc]Tc-PSMA-I&S-SPECT/CT in PCa. RESULTS: [99mTc]Tc-PSMA-I&S-SPECT/CT was performed and evaluated in 210 outpatients with PCa at a single center. Patients were imaged for biochemical recurrence (BCR, n = 152, mean PSA 8.7 ng/ml), for primary staging of high-risk PCa (n = 12, mean PSA 393 ng/ml), and restaging in advanced recurrent PCa (n = 46, mean PSA 101.3 ng/ml). Number and location of positive lesions were determined for the different subgroups. For BCR, detection rates were calculated, defined as the proportion of scans with at least one PSMA-positive lesion. PSMA positive lesions were detected in 65.2% of all 210 patients. Tumor tissue was mainly detected in lymph nodes (59%), in the bone (42%), and in the prostate (fossa) (28%). In the subgroup of patients referred for detection of BCR the detection rate increased from 20% at a PSA level < 1 ng/ml to 82.9% and 100% at PSA levels > 4 ng/ml and > 10 ng/ml, respectively. In the subgroup of high-risk patients referred for primary staging, 42% demonstrated metastatic disease. Restaging of advanced recurrent PCa revealed detectability of PSMA positive tumor lesions in 85% of the scans. CONCLUSIONS: [99mTc]Tc-PSMA-I&S-SPECT/CT was useful in PSMA-targeted imaging of PCa at various clinical stages. At low PSA levels (< 4 ng/ml), detection rates of [99mTc]Tc-PSMA-I&S-SPECT/CT in BCR are clearly inferior to data reported for PET-imaging and should thus only be considered for lesion detection if imaging with PET is unavailable. However, at higher PSA levels (> 4 ng/ml) [99mTc]Tc-PSMA-I&S-SPECT/CT provides high detection rates in BCR. [99mTc]Tc-PSMA-I&S-SPECT/CT can also be used for primary staging and for restaging of advanced recurrent PCa. However, further studies are needed to assess the clinical value in these indications.

From interventionist imaging to intraoperative guidance: New perspectives by combining advanced tools and navigation with radio-guided surgery. / De la imagen intervencionista a la guía intraoperatoria: nuevas perspectivas combinando herramientas avanzadas y navegación con la cirugía radioguiada.

The integration of medical imaging technologies into diagnostic and therapeutic approaches can provide a preoperative insight into both anatomical (e.g. using computed tomography, magnetic resonance imaging, or ultrasound), as well as functional aspects (e.g. using single photon emission computed tomography, positron emission tomography, lymphoscintigraphy, or optical imaging). Moreover, some imaging modalities are also used in an interventional setting (e.g. computed tomography, ultrasound, gamma or optical imaging) where they provide the surgeon with real-time information during the procedure. Various tools and approaches for image-guided navigation in cancer surgery are becoming feasible today. With the development of new tracers and portable imaging devices, these advances will reinforce the role of interventional molecular imaging.

[PET-CT and PET-MRI of the prostate : From 18F-FDG to 68Ga-PSMA]. / PET-CT/-MRT der Prostata : Von 18F-FDG zu 68Ga-PSMA.

CLINICAL/METHODICAL ISSUE: In the last few years nuclear medical diagnostics have experienced a unprecedented renaissance in the diagnostics of prostate cancer, due to the availability of hybrid imaging with positron emission tomography computed tomography (PET/CT), PET magnetic resonance imaging (PET/MRI) and single photon emission computed tomography (SPECT) CT as well as the development of prostate-specific radiopharmaceuticals. METHODICAL INNOVATIONS: The use of fluorodeoxyglucose (FDG), which has been successfully implemented for many years in PET diagnostics, is only helpful in dedifferentiated tumors due to the biological characteristics of prostate cancer. New specific radiopharmaceuticals, such as choline-derivatives, which are incorporated into the prostate cancer cell and built into the cell membrane as well as the recently developed highly specific ligands for prostate-specific membrane antigen (PSMA) are revolutionizing prostate cancer imaging and (re-) staging. PRACTICAL RECOMMENDATIONS: The 68 Ga-labeled PSMA ligands for PET-CT and PET-MRI are highly specific tracers for primary diagnostics and detection of metastases of prostate carcinoma. In risk patients, which includes patients with intermediate and high-risk tumors, they have largely replaced choline-based PET-CT, especially in the case of very low PSA values <0.5 ng/ml in the diagnostics of recurrence. The use in the primary diagnostics as PET-MRI, also in combination with multiparametric MRI (mpMRI), is promising with respect to early diagnostics and image fusion-assisted biopsy as well as surgery and irradiation planning.

Dosimetric measurements of (68)Ga-high affinity DOTATATE: twins in spirit - part III.

PURPOSE: 68Ga-labelled compounds are increasingly used for somatostatin-receptor scintigraphy because of their favourable biokinetic properties, a higher tumour-to-background contrast and higher diagnostic accuracy compared to the gamma-emitting tracer 111In-DTPA-octreotide. Recently, we have introduced the new tracer 68Ga-DOTA-3-iodo-Tyr3-Thr8-octreotide (68Ga-HA-DOTATATE). The present study demonstrates the biodistribution and radiation dosimetry of this tracer in humans. PATIENTS, METHODS: Seven men were enrolled in this analysis. Every patient underwent a 20 min dynamic PET scan after intravenous injection of about 114 ± 9 MBq of 68Ga-HA-DOTATATE. This was followed by two whole-body scans at 30 min p. i. and 120 min p. i. Blood radioactivity concentration was determined non-invasively from a ROI drawn over the aorta. Urine was collected until the time of the last scan. Liver, spleen, kidneys and urinary bladder wall were included in the dosimetric estimation that was carried out with the software package OLINDA 1.0. RESULTS: Physiological 68Ga-HA-DOTATATE uptake was observed in the pituitary gland, thyroid, salivary glands, liver, spleen, kidneys, urinary bladder, adrenals and intestine. Organs with the highest absorbed dose were spleen (0.26 ± 0.11 mSv/MBq), kidneys (0.14 ± 0.03 mSv/MBq) and liver (0.12 ± 0.02 mSv/MBq).The estimated effective dose was 0.024 ± 0.001 mSv/MBq. CONCLUSION: Our study demonstrates biokinetics and radiation exposure of the 68Ga-labelled tracer HA-DOTATATE to be comparable to other 68Ga-labelled SSR analogues in clinical use.

Prediction of glioma recurrence using dynamic ¹8F-fluoroethyltyrosine PET.

BACKGROUND AND PURPOSE: Inter- and intratumor heterogeneity and the variable course of disease in patients with glioma motivate the investigation of new prognostic factors to optimize individual treatment. Here we explore the usefulness of standard static and more sophisticated dynamic (18)F-fluoroethyltyrosine-PET imaging for the assessment of patient prognosis. MATERIALS AND METHODS: Thirty-four consecutive patients with untreated, first-diagnosed, histologically proved glioma were included in this retrospective study. All patients underwent dynamic PET scans before surgery (± standard treatment) and were followed up clinically and by MR imaging. Static and dynamic tumor-to-background ratio, TTP, and slope-to-peak were obtained and correlated with progression-free survival. RESULTS: Twenty of 34 patients experienced progression, with a median progression-free survival of 28.0 ± 11.1 months. Dynamic TTP was highly prognostic for recurrent disease, showing a strong correlation with progression-free survival (hazard ratio, 6.050; 95% CI, 2.11-17.37; P < .001). Most interesting, this correlation also proved significant in the subgroup of low-grade glioma (hazard ratio, 5.347; 95% CI, 1.05-27.20; P = .044), but not when using established static imaging parameters, such as maximum tumor-to-background ratio and mean tumor-to-background ratio. In the high-grade glioma subgroup, both dynamic and static parameters correlated with progression-free survival. The best results were achieved by defining ROIs around "hot spots" in earlier timeframes, underlining the concept of intratumor heterogeneity. CONCLUSIONS: (18)F-fluoroethyltyrosine-PET can predict recurrence in patients with glioma, with dynamic analysis showing advantages over static imaging, especially in the low-grade subgroup.

[[¹¹C]choline as a pharmacodynamic marker for docetaxel therapy. Response assessment in a LNCaP prostate cancer xenograft mouse model]. / Ansprechen auf eine Docetaxeltherapie im LNCaP-Prostatakarzinom-Xenograft-Mausmodell. Untersuchung mit der [¹¹C]Cholin-Kleintier-PET/CT.

UNLABELLED: The AIM of this study was to determine whether [¹¹C]choline can be used for docetaxel therapy response assessment in a LNCaP-prostate cancer xenograft mouse model using [¹¹C]choline small-animal PET/CT. ANIMALS, METHODS: The androgen-dependent human prostate cancer cell line LNCaP was implanted subcutaneously into the left flanks of 17 SCID-mice, 12.5 mg testosterone platelets were implanted in the neck wrinkle. All mice were injected 4-6 weeks after xenograft implantation with 37 MBq [¹¹C]choline via the tail vein. Dynamic imaging was performed for 60 minutes with a small-animal PET/CT scanner. After the first [¹¹C]choline PET/CT imaging 8 mice were subsequently injected intravenously with docetaxel twice (days 1 and 5) at a dose of 3 mg/kg body weight. 8 mice were treated with PBS as a control. [¹¹C]choline PET/CT imaging was performed on day 7, 14 and 21 after treatment. Image analysis was performed using tumor/muscle (T/M) ratios (ROI(T)/ROI(M) = T/M ratio). RESULTS: All LNCaP tumours could be visualized by [¹¹C]choline PET/CT. Before treatment the mean T/M ratio was 2.0 ± 0.2 in the docetaxel-treated group and 1.9 ± 0.2 in the control group (p = 0.837). There was a reduction in the mean [¹¹C]choline uptake after docetaxel treatment of the tumours of the LNCaP cell line as early as 1 week after initiation of therapy (T/M(mean) ratio 1.5 ± 0.2 after one week, 1.3 ± 0.2 after 2 weeks and 1.4 ± 0.2 after 3 weeks). There was no decrease in [¹¹C]choline uptake in the control group. CONCLUSION: Our results show that [¹¹C]choline has the potential for use in the early monitoring of the therapeutic effect of docetaxel in a LNCaP prostate cancer xenograft animal model.

Radiolabelled RGD peptides for imaging and therapy.

Imaging of angiogenesis has become increasingly important with the rising use of targeted antiangiogenic therapies like bevacizumab (Avastin). Non-invasive assessment of angiogenic activity is in this respect interesting, e.g. for response assessment of such targeted antiangiogenic therapies. One promising approach of angiogenesis imaging is imaging of specific molecular markers of the angiogenic cascade like the integrin α(v)ß(3). For molecular imaging of integrin expression, the use of radiolabelled peptides is still the only approach that has been successfully translated into the clinic. In this review we will summarize the current data on imaging of α(v)ß(3) expression using radiolabelled RGD peptides with a focus on tracers already in clinical use. A perspective will be presented on the future clinical use of radiolabelled RGD peptides including an outlook on potential applications for radionuclide therapy.

Comparison of 3'-deoxy-3'-[¹8F]fluorothymidine positron emission tomography (FLT PET) and FDG PET/CT for the detection and characterization of pancreatic tumours.

PURPOSE: Despite recent advances in clinical imaging modalities, differentiation of pancreatic masses remains difficult. Here, we tested the diagnostic accuracy of molecular-based imaging including 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) positron emission tomography (PET) and [(18)F]fluorodeoxyglucose (FDG) PET/CT in patients with suspected pancreatic masses scheduled to undergo surgery. METHODS: A total of 46 patients with pancreatic tumours suspicious for malignancy and scheduled for resective surgery were recruited prospectively. In 41 patients, FLT PET and FDG PET/CT scans were performed. A diagnostic CT performed on a routine basis was available in 31 patients. FLT PET and FDG PET/CT emission images were acquired according to standard protocols. Tracer uptake in the tumour [FDG and FLT standardized uptake value (SUV)] was quantified by the region of interest (ROI) technique. For FDG PET/CT analysis, correct ROI placement was ensured via side-by-side reading of corresponding CT images. RESULTS: Of 41 patients, 33 had malignancy, whereas 8 patients had benign disease. Visual analysis of FDG and FLT PET resulted in sensitivity values of 91% (30/33) and 70% (23/33), respectively. Corresponding specificities were 50% (4/8) for FDG PET and 75% (6/8) for FLT PET. In the subgroup of patients with contrast-enhanced CT (n = 31), sensitivities were 96% (PET/CT), 88% (CT alone), 92% (FDG PET) and 72% (FLT PET), respectively. Mean FLT uptake in all malignant tumours was 3.0 (range SUV(max) 1.1-6.5; mean FDG SUV(max) 7.9, range 3.3-17.8; p < 0.001). CONCLUSION: For differentiation of pancreatic tumours, FDG PET and FDG PET/CT showed a higher sensitivity but lower specificity than FLT PET. Interestingly, visual analysis of FLT PET led to two false-positive findings by misinterpreting physiological bowel uptake as pathological FLT uptake in the pancreas. Due to the limited number of patients, the clinical value of adding FLT PET to the diagnostic workup of pancreatic tumours remains to be determined.

Cryptate mediated nucleophilic 18F-fluorination without azeotropic drying.

UNLABELLED: The radiosynthesis of the vast majority of 18F-labeled tracers rely on azeotropic drying of [18F]fluoride and subsequent cryptate mediated introduction of [18F]fluoride by nucleophilic substitution. THE AIM of this study was to develop a method for simplification of this process, based on preparation of reactive [K(+) is a subset of 2.2.2]18F(-) by solvent drying of [18F]fluoride adsorbed onto an anion exchange resin. METHODS: Aqueous [18F]fluoride (0.5-1 ml) obtained from the 18O(p,n)18F nuclear reaction was trapped on a strong anion-exchange (SAX) cartridge. After washing the cartridge with dry CH3CN, [18F]fluoride was eluted with an anhydrous solution of [K(+) is a subset of 2.2.2]OH(-) in CH3CN and directly used for nucleophilic fluorination reactions. RESULTS: [18F]Fluoride from target water was quantitatively retained by the SAX cartridge, and water-free [18F]fluoride recovered in an overall yield of 92±5% (n = 10). [18F]Fluoride obtained by this procedure led to radiochemical yields of 70-90% for [18F]FDG, [18F]FET, [18F]FLT, [18F]FAZA and [18F]Fallypride. CONCLUSION: SAX-resin adsorbed [18F]fluoride can be dried with non-aqueous solvents and eluted with [K(+) is a subset of 2.2.2]OH(-) in CH3CN. The reactivity of [K(+) is a subset of 2.2.2]F(-) generated by the new method is comparable to that of [18F]fluoride obtained by azeotropic drying. The described procedure facilitates the automated production of 18F-radiopharmaceuticals in general, and may also simplify the use of microfluidic devices for 18F-radiotracer production.

Synthesis, biological evaluation and radiolabelling by 18F-fluoroarylation of a dopamine D3-selective ligand as prospective imaging probe for PET.

Radical (18)F-fluoroarylation with fluorine-18-labelled arenediazonium chlorides has been successfully applied to the radiochemical synthesis of the dopamine D(3)-selective ligand SH 317 ([(18)F]8). SH 317 has been evaluated as a new PET ligand candidate by in vivo experiments.

Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease.

OBJECTIVE: To examine the influence of the APOE genotype on levels of beta-amyloid (Abeta) plaque load and atrophy in patients with Alzheimer disease (AD) in vivo. METHODS: Thirty-two patients with moderate AD were divided into carriers and noncarriers of the epsilon4 allele. These groups were matched for age, disease duration, education, and cognitive impairment. In all subjects, [11C]PIB-PET was performed for measurement of cerebral Abeta plaque deposition and cranial MRI for the assessment of gray matter volume by voxel-based morphometry (VBM) and for correction of partial volume effects (PVE) in the PET data. Voxel-based comparisons (SPM5) were performed between patient groups and healthy control populations and completed with multiple regression analyses between imaging data and epsilon4 allele frequency. RESULTS: Compared to controls, AD-typical patterns of [11C]PIB retention and atrophy were detected in both epsilon4-positive and epsilon4-negative patient groups. In direct comparison, significantly stronger and more extended [11C]PIB uptake was found in epsilon4-positive patients in bilateral temporoparietal and frontal cortex, surviving PVE correction. VBM analysis demonstrated comparable levels of atrophy in both patient groups. Regression analyses revealed a linear association between higher epsilon4 allele frequency and stronger temporoparietal Abeta plaque deposition, independently of other confounds. No major correlation between epsilon4 allele frequency and gray matter decrease was observed. CONCLUSION: These results indicate that the epsilon4-positive APOE genotype not only represents a risk factor for Alzheimer disease (AD), but also results in higher levels of Abeta plaque deposition in epsilon4-positive patients with AD compared to age-matched epsilon4-negative patients with similar levels of cognitive impairment and brain atrophy. The potential role of Abeta plaque imaging for patient inclusion and follow-up in anti-amyloid therapy trials is strengthened by these findings.

Evaluation of the novel myocardial perfusion positron-emission tomography tracer 18F-BMS-747158-02: comparison to 13N-ammonia and validation with microspheres in a pig model.

BACKGROUND: Positron-emission tomography (PET) tracers for myocardial perfusion are commonly labeled with short-lived isotopes that limit their widespread clinical use. 18F-BMS-747158-02 (18F-BMS) is a novel pyridaben derivative that was evaluated for assessment of myocardial perfusion by comparison with 13N-ammonia (13NH3) and with radioactive microspheres in a pig model. METHODS AND RESULTS: Fourteen pigs injected with 500 MBq of 13NH3 or 100 to 200 MBq of 18F-BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of these pigs, 18F-BMS was injected during stress combined with transient, 2.5-minute constriction of the left anterior descending coronary artery. Radioactive microspheres were coinjected with 18F-BMS. Ratios of myocardial tracer uptake to surrounding tissues were determined, and myocardial blood flow was quantified by compartmental modeling. Both tracers showed high and homogeneous myocardial uptake. Compared with 13NH3, 18F-BMS showed higher activity ratios between myocardium and blood (rest 2.5 versus 4.1; stress 2.1 versus 5.8), liver (rest 1.2 versus 1.8; stress 0.7 versus 2.0), and lungs (rest 2.5 versus 4.2; stress 2.9 versus 6.4). Regional myocardial blood flow assessed with 18F-BMS PET showed good correlation (r=0.88, slope=0.84) and agreement (mean difference -0.10 [25th percentile -0.3, 75th percentile 0.1 mL x min(-1) x g(-1)]) with that measured with radioactive microspheres over a flow range from 0.1 to 3.0 mL x min(-1) x g(-1). The extent of defects induced by left anterior descending coronary artery constriction measured by 18F-BMS and microspheres also correlated closely (r=0.63, slope=1.1). CONCLUSIONS: 18F-BMS-747158-02 is a very attractive new PET perfusion tracer that allows quantitative assessment of regional myocardial perfusion over a wide flow range. The long half-life of 18F renders this tracer useful for clinical PET/CT applications in the workup of patients with suspected or proven coronary artery disease.

Peptides, multimers and polymers.

Due to their favorable properties and pharmacokinetics, peptides are often regarded as "agents of choice" for imaging and radiotherapy. Chemical strategies have been developed that allow their site specific labeling with various radionuclides for PET and SPECT, without compromising their biological integrity. Together with the overexpression of a wide range of peptide receptors and binding sites on tumor cells or matrix components, this class of compounds offers multiple imaging applications. Furthermore, radiolabeled peptides have great potential as carrier molecules for site-specific delivery of other signalling units, such as fluorescent moieties, cyctotoxic compounds or metals for magnetic resonance imaging. In addition, great efforts have been made to exploit the favorable characteristics of peptides for the development of larger constructs, such as multimeric ligands, polymer-peptide conjugates and "peptide-coated" liposomes and nanoparticles. Some peptides have already entered clinical routine application; some are currently being evaluated in clinical studies. However, a variety of peptides is still "waiting" to enter the imaging arena. This chapter presents a brief overview of the highly active field of peptide radiopharmaceuticals and the future potential of multimeric and polymeric peptide constructs.

Introduction of functional groups into peptides via N-alkylation.

An optimized protocol for the mild and selective Fukuyama-Mitsunobu reaction was used for mono- and di- N-alkylation on solid support. Thereby, nonfunctionalized aliphatic and aromatic residues are quickly introduced into transiently protected, primary amines of a linear peptide. N-Alkylation can also be used to implement alkyl chains carrying (protected) functionalities suited for subsequent modification. Applicability of this method is demonstrated by various N-alkylated analogues of a cyclic CXCR4 receptor antagonist originally developed by Fujii et. al.

A New Method for Radiosynthesis of C-Labeled Carbamate Groups and its Application for a Highly Efficient Synthesis of the Kappa-Opioid Receptor Tracer [C]GR103545.

(11)C-labeled carbamates can be obtained in a three-component coupling reaction of primary or secondary amines with CO(2) and (11)C-methylation reagents. [(11)C]Methyl-triflate mediated methylation of carbamino adducts provides the corresponding (11)C-labeled carbamate groups in excellent yields under mild conditions (temperatures

Renal accumulation of [111In]DOTATOC in rats: influence of inhibitors of the organic ion transport and diuretics.

AIM: Radiation exposure to the kidney limits therapy with radiometal labelled DOTATOC. This study evaluates the organic anion and cation transport (inhibitors: probenecid and cimetidine/dexamethasone) as well as diuresis (furosemide and mannitol) regarding renal uptake of [(111)In]DOTATOC. METHODS: One hundred eight male Fisher rats were injected with [(111)In]DOTATOC via the tail vein. Prior to activity injection a total of 84 rats underwent injection with probenecid vs. sodium chloride 0.9% (48 rats), cimetidine vs. dexamethasone vs. sodium chloride 0.9% (18 rats), and furosemide vs. mannitol vs. sodium chloride 0.9% (18 rats). Rats were sacrificed at predetermined time points up to 48 h after activity injection. Kidneys, adrenal glands, pancreas, spleen, blood, liver, and muscle were harvested and injected activity per gram tissue was determined. Autoradiographic images of the kidneys were acquired in a total of 24 rats. RESULTS: Probenecid led to a reduction in renal uptake by up to 30% while not significantly changing the activity accumulation in the other organs investigated. This reduction was attributable to the renal cortex (ratio cortex/medulla 1.72 vs. 1.99; p = 0.006). Cimetidine and dexamethasone had no effect in any of the organs. Furosemide led to a 44% increase in renal activity accumulation attributable to enhanced renal medullary uptake (ratio cortex/medulla 1.44 versus 1.69; p = 0.006). Mannitol had no effect on renal activity uptake. CONCLUSION: Inhibition of the organic anion transport by probenecid may help reduce renal uptake regarding therapy with radiometal labelled DOTATOC. The enhancing effect of furosemide may be unfavourable for therapy. The results must be confirmed by human studies.

Tumour hypoxia imaging with [18F]FAZA PET in head and neck cancer patients: a pilot study.

PURPOSE: Hypoxia is an important negative prognostic factor for radiation treatment of head and neck cancer. This study was performed to evaluate the feasibility of use of (18)F-labelled fluoroazomycin arabinoside ([(18)F]FAZA) for clinical PET imaging of tumour hypoxia. METHODS: Eleven patients (age 59.6 +/- 9 years) with untreated advanced head and neck cancer were included. After injection of approximately 300 MBq of [(18)F]FAZA, a dynamic sequence up to 60 min was acquired on an ECAT HR+ PET scanner. In addition, approximately 2 and 4 h p.i., static whole-body PET (n = 5) or PET/CT (n = 6) imaging was performed. PET data were reconstructed iteratively (OSEM) and fused with CT images (either an external CT or the CT of integrated PET/CT). Standardised uptake values (SUVs) and tumour-to-muscle (T/M) ratios were calculated in tumour and normal tissues. Also, the tumour volume displaying a T/M ratio >1.5 was determined. RESULTS: Within the first 60 min of the dynamic sequence, the T/M ratio generally decreased, while generally increasing at later time points. At 2 h p.i., the tumour SUV(max) and SUV(mean) were found to be 2.3 +/- 0.5 (range 1.5-3.4) and 1.4 +/- 0.3 (range 1.0-2.1), respectively. The mean T/M ratio at 2 h p.i. was 2.0 +/- 0.3 (range 1.6-2.4). The tumour volume displaying a T/M ratio above 1.5 was highly variable. At 2 h p.i., [(18)F]FAZA organ distribution was determined as follows: kidney > gallbladder > liver > tumour > muscle > bone > brain > lung. CONCLUSION: [(18)F]FAZA PET imaging appears feasible in head and neck cancer patients, and the achieved image quality is adequate for clinical purposes. Based on our initial results, [(18)F]FAZA warrants further evaluation as a hypoxia PET tracer for imaging of cancer.

Fluorine-18 labeling of peptides and proteins.

The pool of promising peptides worthy of investigation and evaluation for clinical use is continuously filled from different sources. Driven by the promising results obtained with peptides addressing somatostatin-2 receptor positive (sst2+) neuroendocrine tumours, other peptides targeting further receptor systems are being studied and evaluated. Progress in profiling the density and incidence of peptide hormone receptors in human cancer has initiated and will further promote research on the corresponding peptidic binders. In addition, industrial pharmaceutical research will be another significant source of peptides in the future. A recent prognosis revealed that about 50% of the drugs entering clinical trials in the next years will be peptides. The extensive research activities in genomics and proteomics will point out and quantify new and already known target structures upregulated in specific diseases. Based on the knowledge of their endogenous ligands or via selection of suitable candidates by phage display, suitable peptide ligands for e.g. membrane associated receptors can be identified and thus allow targeting of such binding sites. Thus, bioactive peptides specifically addressing relevant molecular targets are expected to become an important class of tracers, also due to the possibility of bridging imaging with therapeutic approaches. In this brief overview a summary of methods and strategies for the 18F-labeling of peptides and proteins is given.

Gender dependent rate of metabolism of the opioid receptor-PET ligand [18F]fluoroethyldiprenorphine.

AIM: The morphinane-derivate 6-O-(2-[(18)F]fluoroethyl)-6-O-desmethyldiprenorphine ([(18)F]FDPN) is a nonselective opioid receptor ligand currently used in positron emission tomography (PET). Correction for plasma metabolites of the arterial input function is necessary for quantitative measurements of [(18)F]FDPN binding. A study was undertaken to investigate if there are gender dependent differences in the rate of metabolism of [(18)F]FDPN. METHODS: The rate of metabolism of [(18)F]FDPN was mathematically quantified by fitting a bi-exponential function to each individual's dynamic metabolite data. RESULTS: No statistically significant gender differences were found for age, weight, body mass index or dose. However, significant differences (p < 0.01) in two of the four kinetic parameters describing the rate of metabolism were found between the two groups, with women metabolizing [(18)F]FDPN faster than men. These differences were found in the contribution of the fast and slow kinetic components of the model describing the distribution of radioactive species in plasma, indicating a higher rate of enzyme-dependent degradation of [(18)F]FDPN in women than in men. CONCLUSION: The findings reinforce the need for individualized metabolite correction during [(18)F]FDPN-PET scans and also indicate that in certain cases, grouping according to gender could be performed in order to minimize methodological errors of the input function prior to kinetic analyses.