Uptake kinetics of the somatostatin receptor ligand [86Y]DOTA-dPhe1-Tyr3-octreotide ([86Y]SMT487) using positron emission tomography in non-human primates and calculation of radiation doses of the 90Y-labelled analogue

[⁹⁰Y]DOTA-dPhe¹-Tyr³-octreotide ([⁹⁰Y]-SMT487) has been suggested as a promising radiotherapeutic agent for somatostatin receptor-expressing tumours. In order to quantify the in vivo parameters of this compound and the radiation doses delivered to healthy organs, the analogue [⁸⁶Y]DOTA-dPhe¹-Tyr³-octreotide was synthesised and its uptake measured in baboons using positron emission tomography (PET). [⁸⁶Y]DOTA-dPhe¹-Tyr³-octreotide was administered at two different peptide concentrations, namely 2 and 100 μg peptide per m² body surface. The latter concentration corresponded to a radiotherapeutic dose. In a third protocol [⁸⁶Y]DOTA-dPhe¹-Tyr³-octreotide was injected in conjunction with a simultaneous infusion of an amino acid solution that was high in l-lysine in order to lower the renal uptake of radioyttrium. Quantitative whole-body PET scans were recorded to measure the uptake kinetics for kidneys, liver, lung and bone. The individual absolute uptake kinetics were used to calculate the radiation doses for [⁹⁰Y]DOTA-dPhe¹-Tyr³-octreotide according to the MIRD recommendations extrapolated to a 70-kg human. The highest radiation dose was received by the kidneys, with 2.1–3.3 mGy per MBq [⁹⁰Y]DOTA-dPhe¹-Tyr³-octreotide injected. For the 100 μg/m² SMT487 protocol with amino acid co-infusion this dose was about 20%–40% lower than for the other two treatment protocols. The liver and the red bone marrow received doses ranging from 0.32 to 0.53 mGy and 0.03 to 0.07 mGy per MBq [⁹⁰Y]DOTA-dPhe¹-Tyr³-octreotide, respectively. The average effective dose equivalent amounted to 0.23–0.32 mSv/MBq. The comparatively low estimated radiation doses to normal organs support the initiation of clinical phase I trials with [⁹⁰Y]DOTA-dPhe¹-Tyr³-octreotide in patients with somatostatin receptor-expressing tumours. Received 26 September and in revised form 18 November 1998     

Measurement of absolute bone blood flow by positron emission tomography

A method of measuring bone blood flow has been developed using ¹⁸F sodium fluoride and positron emission tomography. The blood flow levels are in line with those obtained experimentally from microsphere embolisation. This investigative method could be applied to elucidate a number of clinical questions involving bone perfusion.     

Quantification aspects of patient studies with Fe in positron emission tomography

Quantification accuracy in positron emission tomography (PET) using non-pure positron emitters, such as ⁵²Fe, may be influenced by gamma radiation emitted in the decay of these isotopes. High-energy positrons, emitted in the decay of the ⁵²Fe-daughter ^52mMn, also affect the quantification accuracy. A specific problem of the ⁵²Fe/^52mMn decay chain in vivo is that the kinetics of iron and manganese are different, and that PET cannot discriminate between the two nuclides. The effect of the decay properties of ⁵²Fe/^52mMn on the performance of PET was investigated using phantoms. Minor degradation in PET performance was found for ⁵²Fe/^52mMn compared to the pure low-energy positron emitter ¹⁸F. A method is presented to obtain a correction factor for the ^52mMn radioactivity in blood. A model for correction of ^52mMn-radioactivity in organs, based on existing data on manganese kinetics, is given. The presented corrections are discussed and illustrated in a patient study.     

Alternative positron emission tomography with non-conventional positron emitters: effects of their physical properties on image quality and potential clinical applications

The increasing amount of clinically relevant information obtained by positron emission tomography (PET), primarily with fluorine-18 labelled 2-deoxy-2-fluoro-d-glucose, has generated a demand for new routes for the widespread and cost-efficient use of positron-emitting radiopharmaceuticals. New dual-head single-photon emission tomography (SPET) cameras are being developed which offer coincidence detection with camera heads lacking a collimator or SPET imaging with specially designed collimators and additional photon shielding. Thus, not only satellite PET imaging units but also nuclear medicine units investing in these new SPET/PET systems need to examine all available alternatives for rational radionuclide supplies from host cyclotrons. This article examines 25 ”alternative” positron-emitting radionuclides, discusses the impact of their decay properties on image quality and reviews methods for their production as well as for their application in imaging techniques.     

Delayed cerebral radionecrosis with a high uptake of 11C-methionine on positron emission tomography and 201Tl-chloride on single-photon emission computed tomography

A 47-year-old woman, who 2.5 years previously had undergone resection of a malignant astrocytoma of the left temporal lobe followed by radiotherapy, was found to have a mass in the left frontal lobe. This showed high uptake of thallium-201 (²⁰¹Tl) on single-photon emission computed tomography and ¹¹C-methionine on positron-emission tomography, suggesting recurrent tumour. Histological examination of the resected lesion, however, revealed it to be radionecrosis. This case thus illustrates a diagnostic pitfall in the use of these investigations for distinguishing radionecrosis from recurrent malignant glioma. Received: 19 September 1997 Accepted: 16 October 1997     

Preparation and evaluation of 89Zr-Zevalin for monitoring of 90Y-Zevalin biodistribution with positron emission tomography

Purpose To evaluate whether ⁸⁹Zr can be used as a PET surrogate label for quantification of ⁹⁰Y-ibritumomab tiuxetan (⁹⁰Y-Zevalin) biodistribution and dosimetry before myeloablative radioimmunotherapy.Methods Zevalin was labelled with ⁸⁹Zr by introducing N-succinyldesferal (N-sucDf) as a second chelate. For comparison of the in vitro stability of ⁸⁹Zr-Zevalin and ⁸⁸Y-Zevalin (as a substitute for ⁹⁰Y), samples were incubated in human serum at 37°C up to 6 days. Biodistribution of ⁸⁹Zr-Zevalin and ⁸⁸Y-Zevalin was assessed at 24, 48, 72 and 144 h p.i. by co-injection in nude mice bearing the non-Hodgkin’s lymphoma (NHL) xenograft line Ramos. The clinical performance of ⁸⁹Zr-Zevalin-PET was evaluated via a pilot imaging study in a patient with NHL, who had undergone [¹⁸F]FDG-PET 2 weeks previously.Results Modification of Zevalin with N-sucDf resulted in an N-sucDf-to-antibody molar ratio of 0.83±0.04. After radiolabelling and purification, the radiochemical purity and immunoreactivity of ⁸⁹Zr-Zevalin always exceeded 95% and 80%, respectively. ⁸⁹Zr-Zevalin showed the same stability in serum as ⁸⁸Y-Zevalin, with a radiochemical purity >95% during a period of 6 days. The co-injected ⁸⁹Zr-Zevalin and ⁸⁸Y-Zevalin conjugates showed a very similar biodistribution, except for liver and bone accumulation at 72 and 144 h p.i., which was significantly higher for ⁸⁹Zr than for ⁸⁸Y. PET images obtained after injection of ⁸⁹Zr-Zevalin showed clear targeting of all known tumour lesions.Conclusion ⁸⁹Zr-Zevalin and ⁸⁸Y-Zevalin showed a very similar biodistribution in mice, implying that ⁸⁹Zr-Zevalin-PET might be well suited for prediction of ⁹⁰Y-Zevalin biodistribution in a myeloablative setting.     

Fluorine-18 deoxyglucose positron emission tomography for the detection of bone metastases in patients with non-small cell lung cancer

Despite advances in morphological imaging, some patients with lung cancer are found to have non resectable disease at surgery or die of recurrence within a year of surgery. At present, metastatic bone involvement is usually assessed using bone scintigraphy, which has a high sensitivity but a poor specificity. We have attempted to evaluate the utility of the fluorine-18 deoxyglucose positron emission tomography (FDG PET) for the detection of bone metastasis. One hundred and ten consecutive patients with histological diagnosis of non-small cell lung cancer (NSCLC) who underwent both FDG PET and bone scintigraphy were selected for this review. In this group, there were 43 patients with metastatic disease (stage IV). Among these, 21 (19% of total group) had one or several bone metastases confirmed by biopsy (n = 8) or radiographic techniques (n = 13). Radionuclide bone scanning correctly identified 54 out of 89 cases without osseous involvement and 19 out of 21 osseous involvements. On the other hand, FDG PET correctly identified the absence of osseous involvement in 87 out of 89 patients and the presence of bone metastasis in 19 out of 21 patients. Thus using PET there were two false-negative and two false-positive cases. PET and bone scanning had, respectively, an accuracy of 96% and 66% in the evaluation of osseous involvement in patients with NSCLC. In conclusion, our data suggest that whole-body FDG PET may be useful in detecting bone metastases in patients with known NSCLC. Received 10 March and in revised form 7 May 1998     

Resting state rCBF mapping with single-photon emission tomography and positron emission tomography: magnitude and origin of differences

Single-photon emission tomography (SPET), using technetium-99m hexamethylpropylene amine oxime, and positron emission tomography (PET), using oxygen-15 butanol were compared in six healthy male volunteers with regard to the mapping of resting state regional cerebral blood flow (rCBF). A computerized brain atlas was utilized for 3D regional analyses and comparison of 64 selected and normalized volumes of interest (VOIs). The normalized mean rCBF values in SPET, as compared to PET, were higher in most of the Brodmann areas in the frontal and parietal lobes (4.8% and 8.7% respectively). The average differences were small in the temporal (2.3%) and occipital (1.1%) lobes. PET values were clearly higher in small VOIs like the thalamus (12.3%), hippocampus (12.3%) and basal ganglia (9.9%). A resolution phantom study showed that the in-plane SPET/PET system resolution was 11.0/7.5 mm. In conclusion, SPET and PET data demonstrated a fairly good agreement despite the superior spatial resolution of PET. The differences between SPET and PET rCBF are mainly due to physiological and physical factors, the data processing, normalization and co-registration methods. In order to further improve mapping of rCBF with SPET it is imperative not only to improve the spatial resolution but also to apply accurate correction techniques for scatter, attenuation and non-linear extraction. Received 3 August and in revised form 1 October 1997     

Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism

Parkinsonism is a feature of a number of neurodegenerative diseases, including Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy. The results of post-mortem studies point to dysfunction of the dopaminergic neurotransmitter system in patients with parkinsonism. Nowadays, by using single-photon emission tomography (SPET) and positron emission tomography (PET) it is possible to visualise both the nigrostriatal dopaminergic neurons and the striatal dopamine D₂ receptors in vivo. Consequently, SPET and PET imaging of elements of the dopaminergic system can play an important role in the diagnosis of several parkinsonian syndromes. This review concentrates on findings of SPET and PET studies of the dopaminergic neurotransmitter system in various parkinsonian syndromes.     

Diagnosis of heterotopic bone marrow in the mediastinum using52Fe and positron emission tomography

A patient with hereditary spherocytosis was admitted with mediastinal masses on the chest X-ray.⁵²Fe and positron emission tomography (PET) showed uptake of⁵²Fe in the masses and established the diagnosis of thoracic extramedullary hematopoiesis.This article was presented at the 1st EEC workshop on accuracy determination in PET, January 19–20th, 1989 Pisa, Italy (COMAC-BME Concerted Project Characterization and Standardization of PET instrumentation)     

Imaging of metabolism and autonomic innervation of the heart by positron emission tomography

Positron emission tomography (PET) allows, in combination with multiple radiopharmaceuticals, unique physiological and biochemical tissue characterization. Tracers of blood flow, metabolism and neuronal function have been employed with this technique for research application. More recently, PET has emerged in cardiology as a useful tool for the detection of coronary artery disease and the evaluation of tissue viability. Metabolic tracers such as fluorine-18 deoxyglucose (FDG) permit the specific delineation of ischaemically compromised myocardium. Clinical studies have indicated that the metabolic imaging is helpful in selecting patients for coronary artery bypass surgery or coronary angioplasty. More recent research work has concentrated on the use of carbon-11 acetate as a marker of myocardial oxygen consumption. Together with measurements of left ventricular performance, estimates of cardiac efficiency can be derived from dynamic ¹¹C-acetate studies. The non-invasive evaluation of the autonomic nervous system of the heart was limited in the past. With the introduction of radiopharmaceuticals which specifically bind to neuronal structures, the regional integrity of the autonomic nervous system of the heart can be evaluated with PET. Numerous tracers for pre- and postsynaptic binding sites have been synthesized. ¹¹C-hydroxyephedrine represents a new catecholamine analogue which is stored in cardiac presynaptic sympathetic nerve terminals. Initial clinical studies with it suggest a promising role for PET in the study of the sympathetic nervous system in various cardiac diseases such as cardiomyopathy, ischaemic heart disease and diabetes mellitus. The specificity of the radiopharmaceuticals and the quantitative measurements of tissue tracer distribution provided by PET make this technology a very attractive research tool in the cardiovascular sciences with great promise in the area of cardiac metabolism and neurocardiology.This work was supported by National Institutes of Health grant R01 HL41047-02 and the American Heart Association of Michigan grant 88-0699.Dr. Pierre Mélon is a research fellow supported by the National Foundation for Scientific Research of Belgium and in part by a grant of the Belgian Leon Fredericq Foundation. Offprint requests to: M. Schwaiger     

Radiation dose rates from patients undergoing positron emission tomography: implications for technologists and waiting areas

Increasingly hospitals are showing an interest in developing their imaging services to include positron emission tomography (PET). There is therefore a need to be aware of the radiation doses to critical groups. To assess the effective whole-body dose received by technologists within our dedicated PET centre, each staff member was issued with a dose rate meter, and was instructed to record the time spent in contact with any radioactive source, the dose received per working day and the daily injected activity. On average each technologist administered 831 MBq per day. The mean whole-body dose per MBq injected was 0.02 μSv/MBq^–1. The average time of close contact (<2.0 m) with a radioactive source per day was 32 min. The average effective dose per minute close contact was 0.5 μSv/min^–1, which resulted in a mean daily effective dose of 14.4 μSv. No technologist received greater than 60 μSv (the current UK limit for non-classified workers) in any one day, and in general doses received were less than 24 μSv, the daily dose corresponding to the proposed new annual limit for non-classified workers of 6.0 mSv per annum. However, we recognise that the layout of nuclear medicine departments will not mirror our own. We therefore measured the instantaneous dose rates at 0.1, 0.5, 1.0 and 2.0 m from the mid-thorax on 115 patients immediately after injection, to provide estimates of the likely effective doses that might be received by technologists operating dual-headed coincidence detectionsystems, and others coming into contact in the waiting room with patients who have been injected with fluorine-18 fluorodeoxyglucose. The mean (95th percentile) dose rates measured at the four aforementioned distances were 391.7 (549.5), 127.0 (199.8), 45.3 (70.0) and 17.1 (30.0) μSv/h^–1, respectively. A number of situations have been modelled showing that, with correct planning, FDG studies should not significantly increase the effective doses to technologists. However, one possible area of concern is that, depending on the number of patients in a waiting area at any one time, accompanying persons may approach the limits set by the new UK IRR 1999 regulations for members of the public. Received 30 September and in revised form 27 December 1999     

肺癌的MR全身DWI与PET成像的对照研究

目的：探讨MR DWI及PET成像在肺癌诊断及鉴别诊断中的应用价值。方法：26例临床高度怀疑为肺癌且接受了PET检查的患者行MR DWI检查,通过三维图像重组及黑白翻转技术,得到＂类PET＂图像,观察病变的形态、大小和分布,并与PET影像进行比较,在工作站上测量肺部病变的ADC值及SUV值,进行相关性分析。最终的诊断结果依据影像学检查、病理诊断和随访复查共同确定,其中肺癌19例,肺部炎性假瘤1例,慢性炎症4例,淋巴结反应性增生2例。结果：以病理结果为金标准,PET检出肺癌的敏感度为100%,特异度为57.1%;MR DWI的敏感度为94.7%,特异度为71.2%。肺癌与炎性病变的ADC值及SUV值差异均有统计学意义（P〈0.01）,肺癌病灶的ADC值与SUV值没有明显线性相关关系（r=-0.293,P〉0.05）。结论：MR DWI及PET成像对肺癌的诊断有较高的敏感度及特异度,两种方法互为补充,可为肺癌的诊断及鉴别诊断提供更多的信息。     

Computer tomography, magnetic resonance imaging, and positron emission tomography or positron emission tomography/computer tomography for detection of metastatic lymph nodes in patients with ovarian cancer: a meta-analysis

Objectives

To compare the diagnostic performances of computed tomography (CT), magnetic resonance (MR) imaging, and positron emission tomography (PET or PET/CT) for detection of metastatic lymph nodes in patients with ovarian cancer.

Methods

Relevant studies were identified with MEDLINE and EMBASE from January 1990 to July 2010. We estimated the weighted summary sensitivities, specificities, OR (odds ratio), and summary receiver operating characteristic (sROC) curves of each imaging technique and conducted pair-wise comparisons using the two-sample Z-test. Meta-regression, subgroup analysis, and funnel plots were also performed to explain the between-study heterogeneity.

Results

Eighteen eligible studies were included, with a total of 882 patients. PET or PET/CT was a more accurate modality (sensitivity, 73.2%; specificity, 96.7%; OR [odds ratio], 90.32). No significant difference was detected between CT (sensitivity, 42.6%; specificity, 95.0%; OR, 19.87) and MR imaging (sensitivity, 54.7%; specificity, 88.3%; OR, 12.38). Meta-regression analyses and subgroup analyses revealed no statistical difference. Funnel plots with marked asymmetry suggested a publication bias.

Conclusion

FDG-PET or FDG-PET/CT is more accurate than CT and MR imaging in the detection of lymph node metastasis in patients with ovarian cancer.     

Positron emission tomography/computed tomography for staging and restaging of head and neck cancer: comparison with positron emission tomography read together with contrast-enhanced computed tomography

This retrospective study aimed to describe the differences between image readings done with combined positron emission tomography/computed tomography (PET/CT) and PET read together with contrast-enhanced CT (ceCT) in patients with squamous cell carcinoma of the head and neck. In 46 patients, no differences were found between the two readings for assessing infiltration of adjacent structures (P=.63), transgression of the midline (P=.67), lymph node involvement (P=.32), and T- and N stage. PET/CT and PET read together with ceCT have comparable diagnostic yield.     

The significance of a dipyridamole induced 99mTc-MIBI perfusion abnormality on single photon emission tomography: a quantitative validation with labelled water and positron emission tomography

To relate technetium-99m 2-methoxy-isobutylisonitrile (^99mTc-MIBI) uptake to regional myocardial blood flow (rMBF), ^99mTc-MIBI single photon emission tomography (SPET) and H₂ ¹⁵O positron emission tomography (PET) scans were obtained at rest and after dipyridamole infusion in six patients with single vessel coronary artery disease. ^99mTc-MIBI and H₂ ¹⁵O data sets were created for each segment perfused by the stenotic vessel and for a normal reference area, assigning regions on the SPET tomograms to comparable regions on the PET by similar transaxial image reconstructions. All patients demonstrated post-dipyridamole ^99mTc-MIBI perfusion defects in the territories supplied by the stenotic arteries. Resting rMBF in these regions was slightly lower than that in the normal areas (0.82±0.05 vs 0.90±0.09 ml/g/min, P=NS). A 43%±14% reduction in ^99mTc-MIBI activity in the area at risk was coupled with on average a 60%±9% reduction in post-dipyridamole rMBF compared with control regions (0.98±0.08 vs 2.52±0.51 ml/g/min, P<0.001). Thus, SPET assessment of ^99mTc-MIBI uptake tends to underestimate the perfusion contrast between areas with normal and areas with low coronary vasodilatory reserve when compared to PET. However, these findings may still not affect the clinical usefulness of ^99mTc-MIBI and more extensive studies are required to confirm these results in the clinical environment.     

Quantitative evaluation of manganese-52m as a myocardial perfusion tracer in pigs using positron emission tomography

There is a need for a quantitative myocardial perfusion agent that does not require an on-site cyclotron. Early studies with manganese demonstrated that this trace metal is of potential use for myocardial imaging.^52mMn can be produced in a⁵²Fe-^52mMn generator and is suitable for positron emission tomographic (PET) imaging. The purpose of this study was to evaluate^52mMn with regard to its potential to quantitatively assess myocardial perfusion. Dynamic PET imaging was performed in six pigs with various doses of dipyridamole to increase blood flow. Retention (R) and model-basedK ₁ values were correlated with microsphere blood flow. The models consisted of one (K ₁,k ₂) and two (K ₁,k ₂,k ₃) tissue compartments. Anterior, lateral and septal regions showed a good myocardium-to-background ratio; the evaluation of the inferior wall was impaired by high liver uptake. Linear regression yielded the following equations:K ₁=1.152 flow+0.059 (r=0.92),R=0.069 flow+0.034 (r=0.84). Based on these regressions,K ₁ increased 2.7-fold andR 2.6-fold in the examined flow range of 0.5–2 ml/min/g (fourfold increase), demonstrating an underestimation of higher flow rates by both measures. It is concluded that^52mMn allows the qualitative assessment of myocardial perfusion but does not meet the requirements of a quantitative myocardial perfusion agent.     

The detection of local recurrent head and neck cancer with fluroine-18 fluorodeoxyglucose dual-head positron emission tomography

Primary tumors of the larynx and hypopharynx are preferably treated with high-dose radiation therapy. In these patients, it may be difficult to distinguish recurrent disease from post-treatment reactions. The aim of the present study was to assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in the detection of local relapses of laryngeal or hypopharyngeal carcinoma after radiotherapy using a dual-head PET camera. Forty-eight patients (43 male, 5 female; mean age ±SD, 61±9.5 years) with suspected recurrent laryngeal or hypopharyngeal cancer were prospectively studied. The mean interval between initial treatment and suspicion of recurrent disease was 14.6 months (range: 3–100 months). FDG dual-head PET was followed by endoscopy with or without biopsy under general anaesthesia within a period of 2 months in all patients. The mean period of follow-up after FDG dual-head PET was 13.7 months. In 19 out of 31 patients with focally increased uptake, tumour recurrence (mean diameter: 2.4 cm; range 0.4–6.5 cm) was found at initial endoscopy. In five patients recurrence was found during follow-up with a mean interval of 6.6 months. Seven patients had a false-positive study due to benign lesions or swallowing artefacts. In none of the patients with a normal PET study was tumour recurrence found during follow-up. The sensitivity and specificity of FDG dual-head PET were 100% and 71%, respectively. It is concluded that FDG dual-head PET is highly sensitive for the detection of local recurrence of laryngeal and hypopharyngeal carcinoma after radiotherapy. Some lesions were detected with a mean interval of 6.6 months before histological confirmation. In patients suspected of having recurrent laryngeal or hypopharyngeal cancer in whom FDG-PET is negative, endoscopy may be omitted for at least 6 months and possibly for up to 1 year. Received 27 January and in revised form 15 March 1999     

Rapid detection of human infections with fluorine-18 fluorodeoxyglucose and positron emission tomography: preliminary results

The purpose of this study was to evaluate the feasibility of 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) and positron emission tomography (PET) for rapid detection of human infections. Eleven patients who were known or suspected to be harboring various infections were studied with FDG-PET. Dynamic scans over the putative infection sites were performed immediately after FDG (370 MBq) injection through 60 min, and static images including multiple projection images were then obtained. FDG uptake was assessed visually into four grades (0, normal; 1, probably normal; 2, probably abnormal; 3, definitely abnormal). For the semiquantitative index of FDG uptake in infections, the standardized uptake value of FDG normalized to the predicted lean body mass (SUV-lean, SUL) was determined from the images obtained at 50–60 min after FDG injection. PET results were compared with final clinical diagnoses. Eleven lesions in eight patients, which were interpreted as grade 2 or 3 by FDG-PET, were all concordant with active infectious foci. The SUL values of infections ranged from 0.97 to 6.69. In two patients, FDG-PET correctly showed no active infection. In one patient, it was difficult to detect infectious foci by FDG-PET due to substantial normal background uptake of FDG. In total, FDG-PET correctly diagnosed the presence or absence of active infection in 10 of 11 patients. Fusion images of PET with computed tomography showed the most intense FDG uptake to be within an abscess wall. In conclusion, FDG-PET appears to be a promising modality for rapid imaging of active human infections. More extensive clinical evaluation is warranted to determine the accuracy of this method. Received 5 March and in revised form 20 May 1998