Radiolabelling DOTA-peptides with 68Ga

Purpose A new field of interest is the application of ⁶⁸Ga-labelled DOTA-conjugated peptides for positron emission tomography (PET). The commercially available or house-made generators require time-consuming and tedious handling of the eluate. Radiolabelling at high specific activities without further purification is not possible, while high specific activities are necessary for peptides that potentially display pharmacological side-effects. Here we present the practical aspects and the results of radiolabelling DOTA-peptides with a TiO₂-based commercially available ⁶⁸Ge/⁶⁸Ga generator.Methods Reaction kinetics and parameters influencing the incorporation of the radionuclide at the highest achievable specific activity were investigated. Since high finger doses were anticipated during handling of the high beta-energy emitter ⁶⁸Ga, finger dosimetric measurements were performed during radiolabelling and in vivo administration.Results Fractionated elution of the generator revealed that 80% of the radioactivity was recovered in 1 ml. Bi- and trivalent ionic contaminants that compete for the incorporation of the radionuclide were below 50 nM; thus further tedious and time-consuming purification was avoided. Radiolabelling was performed at pH 3.5–4. Plastic shielding (7-mm wall thickness) around the syringe during administration effectively eliminated the positrons. In rats ⁶⁸GaCl₃ had slow clearance from blood, while ⁶⁸Ga-EDTA was rapidly cleared via the kidneys. Uptake of ⁶⁸Ga-DOTATOC in somatostatin receptor-positive tissues was high, with no significant difference between 1 and 4 h post injection.Conclusion DOTA-peptides for PET imaging can be labelled with ⁶⁸Ga up to specific activities of 1 GBq per nmol within 20 min, enabling the clinical application of peptides that display potential pharmacological side-effects.     

Optimal dose of <Superscript>18</Superscript>F-FDG required for whole-body PET using an LSO PET camera

Reducing the acquisition time of whole-body fluorine-18 fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) (corrected for attenuation) is of major importance in clinical practice. With the introduction of lutetium oxyorthosilicate (LSO), the acquisition time can be dramatically reduced, provided that patients are injected with larger amounts of tracer and/or the system is operated in 3D mode. The aim of this study was to determine the optimal dose of ¹⁸F-FDG required in order to achieve good-to-excellent image quality when a "3-min emission, 2-min transmission/bed position" protocol is used for an LSO PET camera. A total of 218 consecutive whole-body ¹⁸F-FDG PET studies were evaluated retrospectively. After excluding patients with liver metastases, hyperglycaemia and paravenous injections, the final study population consisted of 186 subjects (112 men, 74 women, age 59±15 years). Patients were injected with an activity of ¹⁸F-FDG ranging from 2.23 to 15.21 MBq/kg. Whole-body images corrected for attenuation (3 min emission, 2 min transmission/bed position) were acquired with an LSO PET camera (Ecat Accel,Siemens) 60 min after tracer administration. Patients were positioned with their arms along the body. Image reconstruction was done iteratively and a post-reconstruction filter was applied. Image quality was scored visually by two independent observers using a five-point scoring scale (poor, reasonable, good, very good, excellent). In addition, the coefficient of variability (COV) was measured in a region of interest over the liver in order to quantify noise. Of the images obtained in 118 patients injected with 8 MBq/kg ¹⁸F-FDG, 92% and 90% were classified as good, very good or excellent by observer 1 and observer 2, respectively. The COV averaged 10.63%±3.19% for doses 8 MBq/kg and 16.46%±5.14% for doses <8 MBq/kg. Administration of an ¹⁸F-FDG dose of 8 MBq/kg results in images of good to excellent quality in the vast majority of patients when using an LSO PET camera and applying a 3-min emission, 2-min transmission/bed position acquisition protocol. At lower doses, a rapid decline in image quality and increasing noise are observed. Alternative protocols should be adopted in order to compensate for the loss in image quality when doses <8 MBq/kg are used.     

Intraindividual comparison of <Superscript>68</Superscript>Ga-DOTA-TATE and <Superscript>18</Superscript>F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours

Aim  To compare the diagnostic impact of ⁶⁸Ga-DOTA-TATE and ¹⁸F-DOPA PET in the diagnosis of well-differentiated metastatic neuroendocrine tumours (NET). Methods  PET/CT using both ⁶⁸Ga-DOTA-TATE and ¹⁸F-DOPA was performed in 25 patients with histologically proven metastatic NET (nine gut, five pancreas, six lung, one paranasal sinus, four with unknown primary). Analyses of PET examinations were patient-based (pathological uptake: yes/no), and based on tumour regions (primary tumour if present and metastases of liver, lung, bones and lymph nodes). The results were compared with the results of contrast enhanced CT, and with plasma serotonin levels, which were available in 24 of the 25 patients. Results  Patient-based sensitivities were 96% for ⁶⁸Ga-DOTA-TATE PET and 56% for ¹⁸F-DOPA PET. ⁶⁸Ga-DOTA-TATE PET delineated metastases in 54 of 55 positive metastatic tumour regions in contrast to 29 of 55 delineated by ¹⁸F-DOPA PET. Overall, ⁶⁸Ga-DOTA-TATE was superior to ¹⁸F-DOPA in 13 patients (two patients showed fewer positive tumour regions with ¹⁸F-DOPA PET). The results were comparable in 12 patients. In 13 of 24 patients, plasma serotonin levels were elevated, and 11 of these 13 patients showed pathological uptake of ¹⁸F-DOPA. Of the 11 patients with normal levels of serotonin, 3 also showed positive ¹⁸F-DOPA uptake. In patients positive for ¹⁸F-DOPA uptake the maximum tumour SUVs were correlated with the levels of serotonin (r=0.66, p=0.01). Conclusion  In this study ⁶⁸Ga-DOTA-TATE PET proved clearly superior to ¹⁸F-DOPA PET for detection and staging of NET. ¹⁸F-DOPA uptake tended to be increased in those patients with elevated plasma serotonin. We conclude that ¹⁸F-DOPA PET should be employed in patients with NET with negative ⁶⁸Ga-DOTA-TATE PET and elevated plasma serotonin.     

<Superscript>68</Superscript>Ga-DOTANOC: biodistribution and dosimetry in patients affected by neuroendocrine tumors

Objectives The aim of this work was the evaluation of biodistribution and radiation dosimetry of ⁶⁸Ga-DOTANOC in patients affected by neuroendocrine tumors. Materials and methods We enrolled nine patients (six male and three female) affected by different types of neuroendocrine tumors (NETs). Each patient underwent four whole body positron emission tomography (PET) scans, respectively, at 5, 20, 60, and 120 min after the intravenous injection of about 185 MBq of ⁶⁸Ga-DOTANOC. Blood and urine samples were taken at different time points post injection: respectively, at about 5, 18, 40, 60, and 120 min for blood and every 40–50 min from injection time up to 4 h for urine. The organs involved in the dosimetric evaluations were liver, heart, spleen, kidneys, lungs, pituitary gland, and urinary bladder. Dosimetric evaluations were done using the OLINDA/EXM 1.0 software. Results A physiological uptake of ⁶⁸Ga-DOTANOC was seen in all patients in the pituitary gland, the spleen, the liver, and the urinary tract (kidneys and urinary bladder). Organs with the highest absorbed doses were kidneys . The mean effective dose equivalent (EDE) was . Discussion and conclusions The excretion of the compound was principally via urine, giving dose to the kidney and the urinary bladder wall. As SSTR2 is the most frequently expressed somatostatin receptor and ⁶⁸Ga-DOTANOC has high affinity to it, this compound might play an important role in PET oncology in the future. The dosimetric evaluation carried out by our team demonstrated that ⁶⁸Ga-DOTANOC delivers a dose to organs comparable to, and even lower than, analogous diagnostic compounds.     

[<Superscript>18</Superscript>F]FLT-PET in oncology: current status and opportunities

In recent years, [¹⁸F]-fluoro-3-deoxy-3-L-fluorothymidine ([¹⁸F]FLT) has been developed as a proliferation tracer. Imaging and measurement of proliferation with PET could provide us with a non-invasive staging tool and a tool to monitor the response to anticancer treatment. In this review, the basis of [¹⁸F]FLT as a proliferation tracer is discussed. Furthermore, an overview of the current status of [¹⁸F]FLT-PET research is given. The results of this research show that although [¹⁸F]FLT is a tracer that visualises cellular proliferation, it also has certain limitations. In comparison with the most widely used PET tracer, [¹⁸F]FDG, [¹⁸F]FLT uptake is lower in most cases. Furthermore, [¹⁸F]FLT uptake does not always reflect the tumour cell proliferation rate, for example during or shortly after certain chemotherapy regimens. The opportunities provided by, and the limitations of, [¹⁸F]FLT as a proliferation tracer are addressed in this review, and directions are given for further research, taking into account the strong and weak points of the new tracer.     

The role of <Superscript>18</Superscript>F-FDG PET in characterising disease activity in Takayasu arteritis

Takayasu arteritis (TA) is a rare, sporadic and chronic inflammatory arteritis, which predominantly affects the aorta and its branches. Diagnosis can be difficult and there are limitations to the current diagnostic work-up. By detecting areas of active glucose metabolism present in active vasculitis, imaging with fluorine-18 fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) could potentially have a role in the management of TA. Our aim was to assess this role by reviewing 28 ¹⁸F-FDG PET scans performed on 18 patients suspected of having TA. All patients had full clinical and laboratory assessment, cross-sectional imaging and angiography, and 16/18 satisfied the American College of Rheumatologists criteria for TA. ¹⁸F-FDG PET achieved a sensitivity of 92%, a specificity of 100%, and negative and positive predictive values of 85% and 100% respectively in the initial assessment of active vasculitis in TA. We conclude that ¹⁸F-FDG PET can be used to diagnose early disease, to detect active disease (even within chronic changes) and to monitor the effectiveness of treatment.     

Synthesis and evaluation of a novel 68Ga-chelate-conjugated bisphosphonate as a bone-seeking agent for PET imaging

Introduction

⁶⁸Ga is a positron-emitting nuclide that has significant imaging potential given that, unlike cyclotron-produced ¹⁸F, the isotope can be produced on-site utilizing a ⁶⁸Ge/⁶⁸Ga generator. We recently synthesized a novel bone-seeking agent by coupling a bisphosphonate with the ⁶⁸Ga chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). This study presents a first report on the potential of this ⁶⁸Ga bone-seeking radiopharmaceutical in the detection of bone metastases.

Methods

4-Amino-1-hydroxybutylidene-1,1-bisphosphonate was conjugated with 2-[4,7-di(carboxymethyl)-1,4,7-triazonan-1-yl]pentanedioic acid, yielding 2-[4,7-di(carboxymethyl)-1,4,7-triazonan-1-yl]-5-[(4-hydroxy-4,4-diphosphonobutyl)amino]-5-oxopentanoic acid (NOTA-BP). ⁶⁸Ga-labeled NOTA-BP ([⁶⁸Ga]NOTA-BP) was prepared by complexation of NOTA-BP with [⁶⁸Ga] gallium chloride and evaluated in in vitro experiments, biodistribution experiments and micro-positron emission tomography (PET) imaging experiments.

Results

The labeling of NOTA-BP with ⁶⁸Ga was completed by heating for 10 min. [⁶⁸Ga]NOTA-BP was determined to have a radiochemical purity of over 95%, a high affinity for hydroxyapatite and a high stability in plasma. In in vivo biodistribution experiments, [⁶⁸Ga]NOTA-BP demonstrated high bone uptake potential. Compared with ^99mTc-labeled methylene diphosphonate ([^99mTc]MDP) and [¹⁸F]fluoride, [⁶⁸Ga]NOTA-BP exhibited faster blood clearance and a higher bone-to-blood ratio. In addition, mouse model bone metastasis was detected by micro-PET imaging at 1 h postinjection of [⁶⁸Ga]NOTA-BP.

Conclusion

We have developed a novel ⁶⁸Ga-radiolabeled bone-seeking agent. This [⁶⁸Ga]NOTA-BP complex was found to have a high bone affinity and rapid blood clearance, and may thus prove to be useful as a bone-seeking agent for clinical PET.     

Long-term prognostic value of exercise <Superscript>99m</Superscript>Tc-MIBI SPET myocardial perfusion imaging in patients after percutaneous coronary intervention

The purpose of this study was to evaluate the long-term prognostic value of exercise technetium-99m methoxyisobutylisonitrile (^99mTc-MIBI) single-photon emission tomography (SPET) imaging in patients after percutaneous coronary intervention (PCI). Three hundred and eighteen consecutive post-PCI patients who underwent exercise and rest ^99mTc-MIBI SPET myocardial perfusion imaging (MPI) were followed up for 38±27 months. Patients with early revascularisation (<3 months after MPI) were excluded. A semiquantitative visual analysis employing a 20-segment and four-point scoring system was used to define the summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS). Death and non-fatal myocardial infarction (MI) were considered as hard events, and late revascularisation procedures (3 months after MPI) as soft events. Fifty-one patients (16.0%) suffered from cardiac events during follow-up, including 1 (0.3%) death, 13 (4.1%) non-fatal MIs, 9 (2.8%) coronary artery bypass grafting procedures and 28 (8.8%) PCIs. According to the SPET results, patients were classified into three groups: patients with normal MPI (SSS=0, n=153), patients with irreversible defects (SDS<3 and SRS>1, n=100) and patients with reversible defects (SDS3, n=65). The annual hard cardiac event rate in patients with reversible defects was 3.9%, which was significantly higher than that in patients with normal MPI (0.2%, ²=7.71; P<0.01). The annual soft cardiac event rate in patients with reversible defects was 10.7%, which was significantly higher than that in patients with irreversible defects (2.5% ²=17.69; P<0.001), and also significantly higher than that in patients with normal MPI (1.5%, ²=33.89; P<0.001). In patients with normal and reversible defects, there was no significant difference in soft and hard cardiac event rates according to whether patients were symptomatic or asymptomatic (P>0.05). However, the annual soft event rate in patients with irreversible defects and symptoms was 5.0%, which was higher than that of 0.6% in asymptomatic patients (²=6.11, P<0.05). Multivariate Cox analysis showed that SSS was the best independent predictor for hard cardiac events (²=12.70; P<0.001) and SDS was the strongest independent predictor for soft cardiac events (²=11.72; P<0.001). Post-PCI patients who have normal exercise ^99mTc-MIBI SPET MPI have a good long-term prognosis, while those with reversible defects are at a higher risk for future cardiac events, without correlation to the chest pain symptoms. However, symptomatic patients with irreversible defects have a higher risk for repeat revascularisation, but not for hard events, compared with asymptomatic patients. Exercise ^99mTc-MIBI SPET MPI has important clinical value for risk stratification and management decision-making in post-PCI patients.     

[<Superscript>68</Superscript>Ga]DOTATATE PET/MRI and [<Superscript>18</Superscript>F]FDG PET/CT are complementary and superior to diffusion-weighted MR imaging for radioactive-iodine-refractory differentiated thyroid cancer

Purpose

The purpose of this study was to determine whether [⁶⁸Ga]DOTATATE PET/MRI with diffusion-weighted imaging (DWI) can replace or complement [¹⁸F]FDG PET/CT in patients with radioactive-iodine (RAI)-refractory differentiated thyroid cancer (DTC).

Methods

The study population comprised 12 patients with elevated thyroglobulin and a negative RAI scan after thyroidectomy and RAI remnant ablation who underwent both [¹⁸F]FDG PET/CT and [⁶⁸Ga]DOTATATE PET/MRI within 8 weeks of each other. The presence of recurrent cancer was evaluated on a per-patient, per-organ and per-lesion basis. Histology, and prior and follow-up examinations served as the standard of reference.

Results

Recurrent or metastatic tumour was confirmed in 11 of the 12 patients. [⁶⁸Ga]DOTATATE PET(/MRI) correctly identified the tumour burden in all 11 patients, whereas in one patient local relapse was missed by [¹⁸F]FDG PET/CT. In the lesion-based analysis, overall lesion detection rates were 79/85 (93 %), 69/85 (81 %) and 27/82 (33 %) for [¹⁸F]FDG PET/CT, [⁶⁸Ga]DOTATATE PET/MRI and DWI, respectively. [¹⁸F]FDG PET(/CT) was superior to [⁶⁸Ga]DOTATATE PET(/MRI) in the overall evaluation and in the detection of pulmonary metastases. In the detection of extrapulmonary metastases, [⁶⁸Ga]DOTATATE PET(/MRI) showed a higher sensitivity than [¹⁸F]FDG PET(/CT), at the cost of lower specificity. DWI achieved only poor sensitivity and was significantly inferior to [¹⁸F]FDG PET in the lesion-based evaluation in the detection of both extrapulmonary and pulmonary metastases.

Conclusion

[¹⁸F]FDG PET/CT was more sensitive than [⁶⁸Ga]DOTATATE PET/MRI in the evaluation of RAI-refractory DTC, mostly because of its excellent ability to detect lung metastases. In the evaluation of extrapulmonary lesions, [⁶⁸Ga]DOTATATE PET(/MRI) was more sensitive and [¹⁸F]FDG PET(/CT) more specific. Furthermore, DWI did not provide additional information and cannot replace [¹⁸F]FDG PET for postoperative monitoring of patients with suspected RAI-refractory DTC.

     

A single-strip mini-paper chromatographic method for rapid purity-control of 99mTc-labeled radiopharmaceuticals

A single-strip miniaturized paper chromatographic method (Mini-PC) was developed using 80%–90% acetone solvent for rapid purity-control of ^99mTc-radiopharmaceuticals. Routine ^99mTc-radiopharmaceuticals (eight kinds of kit made agents) and diluted agents (in which radiochemical impurities might be formed) were analyzed by Mini-PC and other methods. This showed that, compared with the other methods, the Mini-PC technique is useful for the simple and rapid routine analysis of radiochemical impurities of kit made ^99mTc-radiopharmaceuticals.     

Tetrafluorophenolate of HBED-CC: a versatile conjugation agent for <Superscript>68</Superscript>Ga-labeled small recombinant antibodies

Purpose  The success of ⁶⁸Ga-labeled peptides for positron emission tomography of neuroendocrine tumors is mainly depending on the complex chemistry of this radioisotope. 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), the chelator of choice has however limitations if its application is expanded to heat-sensitive proteins. Recombinant antibodies like single chain Fv or diabodies belong to this class of proteins. They are suited to provide imaging contrast despite the short-lived ⁶⁸Ga because of their rapid blood clearances and nanomolar affinities. The heterobifunctional agent N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid (HBED-CC) was chosen as an alternative ligand because this agent is complexing [⁶⁸Ga]Ga³⁺ much faster than DOTA at ambient temperatures. Materials and methods  A versatile technology for HBED-CC conjugation of proteins and ⁶⁸Ga-labeling has been developed. This included HBED-CC–tetrafluorophenol (TFP) ester synthesis, coupling to the antibody at various pH and complexation reactions performed in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer under different conditions. Results  The synthesis of the monoreactive 2,3,5,6-tetrafluorophenolate of HBED-CC at a carboxyl group not participating in complex formation used [Fe(HBED-CC)]⁻ for ester formation. The removal of Fe³⁺ from purified (HBED-CC)TFP ester was achieved with RP₁₈ cartridge technology. The conjugation chemistry was performed with mAb425 which binds to the epidermal growth factor receptor (EGFR). This protein was used for optimizing purposes only. The influence of complexation parameters like temperature, pH, reaction time, and HBED-CC/antibody ratio on the biological activity of this model antibody was investigated. Furthermore, the outcome of this labeling procedure on the biological activity of a recombinant diabody (50 kDa) was studied. Conclusion  It is known that small HBED-CC/antibody ratios are prerequisites for minimal interference of labels with antigen-binding domains. Here, the coupling of about one HBED-CC per antibody proved to be sufficient for efficient ⁶⁸Ga labeling, pointing to the successful application of ⁶⁸Ga for molecular imaging with small recombinant proteins.     

Evaluation of 111In labelled white blood cells by in vitro functional tests and electron microscopy

We have studied the influence of granulocyte labelling with commercially available ¹¹¹In-oxine, tropolone (trop) or home made ¹¹¹In-Mercapto pyridine (Merc) prepared by the method of Thakur (1985) on the cell structure by electron microscopy and on the cell function by enzymatic tests, random migration, chemotaxis, phagocytosis and bactericidal activity. The granulocytes were labelled with 400 Ci ¹¹¹In-oxine in saline or ¹¹¹In-trop or Merc in plasma. The effect of the chelating agents with and without addition of the tracer was studied (n=4) with varying concentrations: 5–10 g/ml oxine, 10–160 g/ml trop and 1–4 g/ml Merc. Chemotaxis and random migration were not affected by ¹¹¹In-trop and clearly supressed by ¹¹¹In-oxine and Merc; the other tests were normal. The cell structure was disturbed by Merc. The labelling efficiency was excellent with oxine (90%), acceptable with trop (30%–80%) and poor with Merc (10%–25%). Without ¹¹¹In, chemotaxis and random migration were normal up to a concentration of 80 g/ml trop, 8.5 g/ml oxine and 1 g/ml Merc. With addition of ¹¹¹In, chemotaxis and random migration were unaffected up to 80 gmg/ml by trop and markedly supressed by Merc and oxine. It is concluded that labelling with ¹¹¹In-trop assures intact cells.     

Cyclotron production of carrier-free 66Ga as a positron emitting label of albumin colloids for clinical use

A method for producing carrier free ⁶⁶Ga (T_1/2:9.4h; ⁺) by ⁴He bombardment of natural copper targets is presented. ⁶⁶Ga is formed by means of the ⁶³Cu (⁴He, n) ⁶⁶Ga reaction. Production yields are given in the 17.5 to 8 MeV ⁴He energy range. Chemical purification of ⁶⁶Ga from the copper target is described. The only radionuclidic impurity found in the final product was ⁶⁷Ga. Albumin colloids from commercially available kits designed for use with ^99mTc could easily be labeled with ⁶⁶Ga and employed for studies of the lymphatic system by positron emission tomography.     

The dopamine D<Subscript>2</Subscript> receptor ligand <Superscript>18</Superscript>F-desmethoxyfallypride: an appropriate fluorinated PET tracer for the differential diagnosis of parkinsonism

For therapeutic and prognostic reasons it is important to differentiate between idiopathic parkinsonian syndrome (IPS, Parkinsons disease) and atypical parkinsonian syndromes (APS) like multiple system atrophy or progressive supranuclear palsy. Whereas IPS patients usually show a normal or upregulated postsynaptic dopamine D₂ receptor profile, APS patients present decreased postsynaptic tracer binding. The aim of this prospective study was to evaluate the D₂ receptor antagonist fluorine-18 desmethoxyfallypride (¹⁸F-DMFP), a recently developed positron emission tomography (PET) tracer with better clinical availability than carbon-11 raclopride, for the differential diagnosis of IPS versus APS. The study included 16 healthy control subjects and 35 patients with clinically diagnosed parkinsonism (16 IPS patients, 19 APS patients). All patients underwent PET imaging after injection of 180–200 MBq ¹⁸F-DMFP. Receiver operating characteristic (ROC) analyses were performed in order to assess the diagnostic performance of ¹⁸F-DMFP PET. We found the striatal ¹⁸F-DMFP uptake ratio to be significantly (P<0.01) reduced in the APS patients (2.44±0.42) compared with the healthy control subjects (3.61±0.43) and the IPS patients (3.21±0.78), whereas the uptake ratios of the IPS patients and the control subjects did not differ significantly. For the differential diagnosis of APS versus IPS, the ROC analysis of caudate ¹⁸F-DMFP binding showed a specificity, sensitivity and accuracy of 100%, 74% and 86%, respectively, as well as positive and negative predictive values of 100% and 76%, respectively. Based on these first clinical results, we consider ¹⁸F-DMFP to be an appropriate PET tracer for the differential diagnosis of parkinsonian syndromes, with the advantage of better clinical availability than ¹¹C-labelled D₂ radioligands.     

Incremental predictive value of myocardial scintigraphy with<Superscript> 123</Superscript>I-BMIPP in patients with acute myocardial infarction treated with primary percutaneous coronary intervention

Purpose It is unclear whether ¹²³I-labelled -methyl iodophenyl pentadecanoic acid (¹²³I-BMIPP) myocardial scintigraphy adds further predictive value for future cardiac events compared with the variables obtained during cardiac catheterisation in patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI). We therefore investigated whether ¹²³I-BMIPP imaging in patients with AMI treated by primary PCI was useful in predicting future cardiac events.Methods One hundred and fifty-nine patients with AMI who were treated with primary PCI and underwent left ventriculography (LVG) on admission underwent ²⁰¹Tl and ¹²³I-BMIPP myocardial scintigraphy. Scintigrams were visually classified, and the total defect score (TDS) was calculated. Major adverse cardiac events (MACE) were defined as cardiac death including sudden death, congestive heart failure and recurrence of acute coronary syndrome. Patients were followed up for a mean of 34.5 months (12–63 months).Results Twenty-six patients had MACE. Kaplan-Meier analysis indicated that patients with the top 50% of ¹²³I-BMIPP TDSs had a significantly higher rate of MACE (P=0.007). Patients with mismatch between ²⁰¹Tl and ¹²³I-BMIPP images also had significantly more MACE (P=0.02). In the prediction of MACE, the global chi-square value was 5.2 (P=0.001) based on LVEF (<45%) and the number of diseased vessels (two or three). Adding ¹²³I-BMIPP TDS and the mismatch improved the global chi-square value ( ²=7.2)Conclusion Myocardial scintigraphy using ²⁰¹Tl and ¹²³I-BMIPP predicts future cardiac events in patients with AMI treated with primary PCI, and provides additional predictive value compared with the variables obtained with cardiac catheterisation alone.     

Maturation of a key resource - the germanium-68/gallium-68 generator: development and new insights

(68)Ge/(68)Ga radionuclide generators have been investigated for almost fifty years, since the cyclotron-independent availability of positron emitting (68)Ga via the (68)Ge/(68)Ga system had always attracted researches working in basic nuclear chemistry as well as radiopharmaceutical chemistry. However, it took decades and generations of research (and researchers) to finally reach a level of (68)Ge/(68)Ga radionuclide generator designs adequate to the modern requirements of radiometal labelling chemistry. Nevertheless, most of the existing commercial generator systems address aspects of (68)Ge breakthrough and safe synthesis of (68)Ga radiopharmaceuticals by adopting eluate post-processing technologies. Among the strategies to purify (68)Ga eluates, the cation exchange based version is relevant in terms of purification efficiency. In addition, it offers more options towards further developments of (68)Ga radiopharmaceuticals. Today, one may expect that the (68)Ge/(68)Ga radionuclide generator systems could contribute to the clinical impact of nuclear medicine diagnoses for PET similar to the established (99)Mo/(99m)Tc generator system for SPECT. The exciting perspective for the (68)Ge/(68)Ga radionuclide generator system, in turn, asks for systematic chemical, radiochemical, technological and radiopharmaceutical efforts, to guarantee reliable, highly-efficient and medically approved (68)Ge/(68)Ga generator systems.     

The impact of [<Superscript>68</Superscript>Ga]PSMA I&amp;T PET/CT on radiotherapy planning in patients with prostate cancer

Purpose

To determine the impact of Gallium-68-labled prostate-specific membrane antigen positron-emission tomography/computed tomography ([⁶⁸Ga]PSMA PET/CT) on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer.

Methods

A total of 106 patients with prostate cancer scheduled for radiation therapy underwent 120 [⁶⁸Ga]PSMA PET/CT scans prior to radiotherapy treatment. In 20 cases, patients underwent [⁶⁸Ga]PSMA PET/CT for primary therapy (PT), 75 cases were referred for biochemical relapse after surgery (RL), and 25 cases were intended for palliative treatment of localized metastases (MD). We retrospectively compared the impact of [⁶⁸Ga]PSMA PET/CT on lesion detection and treatment decision to CT alone.

Results

[⁶⁸Ga]PSMA PET/CT revealed a total of 271 positive lesions, whereas CT detected 86 lesions (32%). Overall, the radiotherapy regime was changed in 55 of 120 cases (46%) based on the higher detection rate of [⁶⁸Ga]PSMA PET/CT: in 15% of cases with PT, in 43% of cases with RL, and in 44% of cases with MD.

Conclusion

[⁶⁸Ga]PSMA PET/CT is superior to CT alone for lesion detection in prostate cancer, thereby significantly impacting on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer.

     

Detection rate of PET/CT in patients with biochemical relapse of prostate cancer using [<Superscript>68</Superscript>Ga]PSMA I&amp;T and comparison with published data of [<Superscript>68</Superscript>Ga]PSMA HBED-CC

Purpose

To determine the detection rate of PET/CT in biochemical relapse of prostate cancer using [⁶⁸Ga]PSMA I&T and to compare it with published detection rates of [⁶⁸Ga]PSMA HBED-CC.

Methods

We performed a retrospective analysis in 83 consecutive patients with documented biochemical relapse after prostatectomy. All patients underwent whole body [⁶⁸Ga]PSMA I&T PET/CT. PET/CT images were evaluated for presence of local recurrence, lymph node metastases, and distant metastases. Proportions of positive PET/CT results were calculated for six subgroups with increasing prostate specific antigen (PSA) levels (<0.5 ng/mL, 0.5 to <1.0 ng/mL, 1.0 to <2.0 ng/mL, 2.0 to <5.0 ng/mL, 5.0 to <10.0, ≥10.0 ng/mL). Detection rates of [⁶⁸Ga]PSMA I&T were statistically compared with published detection rates of [⁶⁸Ga]PSMA HBED-CC using exact Fisher’s test.

Results

Median PSA was 0.81 (range: 0.01 – 128) ng/mL. In 58/83 patients (70 %) at least one [⁶⁸Ga]PSMA I&T positive lesion was detected. Local recurrent cancer was present in 18 patients (22 %), lymph node metastases in 29 patients (35 %), and distant metastases in 15 patients (18 %). The tumor detection rate was positively correlated with PSA levels, resulting in detection rates of 52 % (<0.5 ng/mL), 55 % (0.5 to <1.0 ng/mL), 70 % (1.0 to <2.0 ng/mL), 93 % (2.0 to <5.0 ng/mL), 100 % (5.0 to <10.0 ng/mL), and 100 % (≥10.0 ng/mL). There was no significant difference between the detection rate of [⁶⁸Ga]PSMA I&T and published detection rates of [⁶⁸Ga]PSMA HBED-CC (all

Conclusions

[⁶⁸Ga]PSMA I&T PET/CT has high detection rates of recurrent prostate cancer that are comparable to [⁶⁸Ga]PSMA HBED-CC.

     

The performance of<Superscript> 18</Superscript>F-fluorodeoxyglucose positron emission tomography in small solitary pulmonary nodules

Solitary pulmonary nodule (SPN, intraparenchymal lung mass <3 cm) is often a diagnostic challenge. This study was performed to evaluate the diagnostic accuracy of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET) in radiologically indeterminate SPN 10 mm on spiral CT. Between August 1997 and March 2001, we identified all patients with radiologically indeterminate SPNs 10 mm who were referred for FDG PET imaging at the VU University Medical Centre. All PET scans were retrospectively reviewed by an experienced nuclear medicine physician. PET was considered positive in cases with at least moderately enhanced focal uptake, and otherwise as negative. Lesions were considered benign on the basis of histology, no growth during 1.5 years or disappearance within at least 6 months. Thirty-five patients with 36 SPNs 10 mm in diameter at clinical presentation were identified (one patient had two metachronous lesions). In 13 of 14 malignant nodules and in two of 22 benign nodules, diagnosis was confirmed by histology. Prevalence of malignancy was 39%. PET imaging correctly identified 30 of 36 small lesions. One lesion proved to be false negative on PET (CT: 10 mm), and in five lesions, PET scans proved to be false positive. Specificity was 77% (17/22; 95% CI: 0.55–0.92), sensitivity 93% (13/14; 95% CI: 0.66–1.0), positive predictive value 72% (13/18; 95% CI: 0.46–0.90) and negative predictive value 94% (17/18; 95% CI: 0.73–1.0). This retrospective study suggests that FDG PET imaging could be a useful tool in differentiating benign from malignant SPNs 10 mm in diameter at clinical presentation. Such results may help in the design of larger prospective trials with structured clinical work-up.     

Correlation of immunohistopathological expression of somatostatin receptor 2 with standardised uptake values in <Superscript>68</Superscript>Ga-DOTATOC PET/CT

Purpose  In clinical routine somatostatin analogue positron emission tomography/computed tomography (PET/CT) such as ⁶⁸Ga-DOTA-Tyr-octreotide (DOTATOC)-PET/CT could substitute conventional ¹¹¹In-Octreotide scintigraphy. Immunohistochemistry (IHC) for somatostatin receptor 2 (SSTR2) might be a tool to predict positivity of ⁶⁸Ga-DOTATOC in patients where initial staging was not performed, e.g., in incidental findings. We therefore compared a score of SSTR2-IHC with the in vivo standard uptake value (SUV) of preoperative or prebiopsy ⁶⁸Ga-DOTATOC PET/CT. Materials and methods  In 18 patients, ⁶⁸Ga-DOTATOC PET/CT scans were quantified with SUV calculations and correlated to a cell membrane-based SSTR2-IHC score (ranging from 0 to 3). Results  Negative IHC scores were consistent with SUV values below 10. Furthermore, all score 2 and 3 specimens corresponded with high SUV values (above 15). Conclusion  SSTR2-IHC scores correlated well with SUV values and we propose to use SSTR2 immunohistochemistry in patients missing a preoperative PET scan to indicate ⁶⁸Ga-DOTATOC-PET/CT as method for restaging and follow-up in individual patients.