Do androgens control the uptake of <Superscript>18</Superscript>F-FDG, <Superscript>11</Superscript>C-choline and <Superscript>11</Superscript>C-acetate in human prostate cancer cell lines?

Purpose  

The aim of this study was to evaluate the impact of androgen ablation therapy in different prostate cancer (PCa) cell lines—reflecting different stages of the disease—on ¹⁸F-fluorodeoxyglucose (FDG), ¹¹C-choline and ¹¹C-acetate uptake.     

<Superscript>68</Superscript>Ga- and <Superscript>111</Superscript>In-labelled DOTA-RGD peptides for imaging of αvβ3 integrin expression

PURPOSE: alphavbeta3 integrins are important cell adhesion receptors involved in angiogenic processes. Recently, we demonstrated using [(18)F]Galacto-RGD that monitoring of alphavbeta3 expression is feasible. Here, we introduce (68)Ga- and (111)In-labelled derivatives and compare them with [(18)F]Galacto-RGD. METHODS: For radiolabelling, cyclo(RGDfK(DOTA)) was synthesised using SPPS. For in vitro characterisation determination of partition coefficients, protein binding, metabolic stability, alphavbeta3 affinity and cell uptake and for in vivo characterization, biodistribution studies and micro positron emission tomography (PET) imaging were carried out. For in vivo and in vitro studies, human melanoma M21 (alphavbeta3 positive) and M21-L (alphavbeta3 negative) cells were used. RESULTS: Both tracers can be synthesised straightforward. The compounds showed hydrophilic properties and high metabolic stability. Up to 23% protein-bound activity for [(68)Ga]DOTA-RGD and only up to 1.4% for [(111)In]DOTA-RGD was found. Cell uptake studies indicate receptor-specific accumulation. This is confirmed by the biodistribution data. One hour p.i. accumulation in alphavbeta3-positive tumours was 2.9 +/- 0.3%ID/g and in alphavbeta3-negative tumours 0.8 +/- 0.1%ID/g for [(68)Ga]DOTA-RGD ([(111)In]DOTA-RGD: 1.9 +/- 0.3%ID/g and 0.5 +/- 0.2%ID/g; [(18)F]Galacto-RGD: 1.6 +/- 0.2%ID/g and 0.4 +/- 0.1%ID/g). Thus, tumour uptake ratios were comparable. Due to approx. 3-fold higher blood pool activities for [(68)Ga]DOTA-RGD, tumour/blood ratios were higher for [(111)In]DOTA-RGD and [(18)F]Galacto-RGD. However, microPET studies demonstrated that visualisation of alphavbeta3-positive tumours using [(68)Ga]DOTA-RGD is possible. CONCLUSIONS: Our data indicate that [(68)Ga]DOTA-RGD allows monitoring of alphavbeta3 expression. Especially, the much easier radiosynthesis compared to [(18)F]Galacto-RGD would make it an attractive alternative. However, due to higher blood pool activity, [(18)F]Galacto-RGD remains superior for imaging alphavbeta3 expression. Introduction of alternative chelator systems may overcome the disadvantages.     

Clinical results of radionuclide therapy of neuroendocrine tumours with <Superscript>90</Superscript>Y-DOTATATE and tandem <Superscript>90</Superscript>Y/<Superscript>177</Superscript>Lu-DOTATATE: which is a better therapy option?

Purpose  

Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues is a treatment option for patients with disseminated neuroendocrine tumours (NET). A combination treatment using the high-energy ⁹⁰Y beta emitter for larger lesions and the lower energy ¹⁷⁷Lu for smaller lesions has been postulated in the literature.The aim of the study was to evaluate combined ⁹⁰Y/¹⁷⁷Lu-DOTATATE therapy in comparison to ⁹⁰Y-DOTATATE alone.     

<Superscript>99m</Superscript>Tc-tetrofosmin or <Superscript>99m</Superscript>Tc-sestamibi for double-phase parathyroid scintigraphy?

Several years ago technetium-99m tetrofosmin was reported to localise parathyroid adenomas. The aim of this study was to compare the sensitivity of this radiopharmaceutical with that of (99m)Tc-sestamibi using a double-phase parathyroid scintigraphy protocol. Scans of 12 patients were evaluated visually and lesion to thyroid ratios were calculated. Nine of the patients were subsequently operated on; a total of eight parathyroid adenomas or hyperplastic glands were histologically confirmed in seven of the patients, while in one patient a parathyroid carcinoma was histologically proven. All of these patients had positive (99m)Tc-sestamibi scintigrams, whereas only two (99m)Tc-tetrofosmin scintigrams were positive. With (99m)Tc-sestamibi there was a significant increase in the lesion to thyroid ratio from 10 min to 90 min and 150 min p.i. which was not seen on scintigraphy with (99m)Tc-tetrofosmin. This makes (99m)Tc-tetrofosmin less suitable for double-phase parathyroid scintigraphy.     

Positron emission tomography imaging of adrenal masses: <Superscript>18</Superscript>F-fluorodeoxyglucose and the 11β-hydroxylase tracer <Superscript>11</Superscript>C-metomidate

Purpose ¹¹C-metomidate (MTO), a marker of 11-hydroxylase, has been suggested as a novel positron emission tomography (PET) tracer for adrenocortical imaging. Up to now, experience with this very new tracer is limited. The aims of this study were (1) to evaluate this novel tracer, (2) to point out possible advantages in comparison with ¹⁸F-fluorodeoxyglucose (FDG) and (3) to investigate in vivo the expression of 11-hydroxylase in patients with primary aldosteronism.Methods Sixteen patients with adrenal masses were investigated using both MTO and FDG PET imaging. All patients except one were operated on. Five patients had non-functioning adrenal masses, while 11 had functioning tumours(Cushings syndrome, n=4; Conns syndrome, n=5; phaeochromocytoma, n=2). Thirteen patients had benign disease, whereas in three cases the adrenal mass was malignant (adrenocortical cancer, n=1; malignant phaeochromocytoma, n=1; adrenal metastasis of renal cancer, n=1).Results MTO imaging clearly distinguished cortical from non-cortical adrenal masses (median standardised uptake values of 18.6 and 1.9, respectively, p<0.01). MTO uptake was slightly lower in patients with Cushings syndrome than in those with Conns syndrome, but the difference did not reach statistical significance. The expression of 11-hydroxylase was not suppressed in the contralateral gland of patients with Conns syndrome, whereas in Cushings syndrome this was clearly the case. The single patient with adrenocortical carcinoma had MTO uptake in the lower range.Conclusion MTO could not definitely distinguish between benign and malignant disease. FDG PET, however, identified clearly all three study patients with malignant adrenal lesions. We conclude: (1) MTO is an excellent imaging tool to distinguish adrenocortical and non-cortical lesions; (2) the in vivo expression of 11-hydroxylase is lower in Cushings syndrome than in Conns syndrome, and there is no suppression of the contralateral gland in primary aldosteronism; (3) for the purpose of discriminating between benign and malignant lesions, FDG is the tracer of choice.     

Myocardial kinetics of <Superscript>201</Superscript>Thallium, <Superscript>99m</Superscript>Tc-tetrofosmin,and <Superscript>99m</Superscript>Tc-sestamibi in an acute ischemia–reperfusion model using isolated rat heart

Objective ²⁰¹Thallium (TL), ^99mTc-tetrofosmin (TF), and ^99mTc-sestamibi (MIBI) are extensively used as myocardial perfusion agents. The objective of the present study was to evaluate their kinetics under acute ischemia–reperfusion. Methods Isolated rat hearts, perfused by the Langendorff method at a constant flow rate of 10 ml/min, were allotted to normal control, mild ischemia, and severe ischemia groups, in which 20-min tracer wash-in was conducted followed by a 25-min tracer washout. No-flow ischemia (15 min for mild ischemia groups; 30 min for severe ischemia groups) was induced before conducting wash-in and washout in the ischemia groups. Whole-heart radioactivity was determined with an external gamma detector. Myocardial flow rate (K ₁, ml/min) and clearance rate (k ₂, min⁻¹) were calculated. Results K _1TL, K _1TF, and K _1MIBI decreased according to the severity of ischemia (K _1TL 5.32 ± 0.53, 4.76 ± 0.70, and 1.44 ± 0.59; K _1TF 3.80 ± 0.70, 2.73 ± 0.99, and 1.09 ± 0.45; and K _1MIBI 3.45 ± 1.10, 2.15 ± 0.82, and 1.05 ± 0.13, in the normal control, mild, and severe ischemia groups, respectively). K ₁ was significantly higher for TL than for the ^99mTc tracers (P < 0.05), but the ^99mTc tracers had equivalent K ₁ values. k _2TL increased significantly (P < 0.05) in the ischemia groups (k _2TL 0.062 ± 0.013, 0.11 ± 0.045, and 0.12 ± 0.035), but showed no significant difference between the ischemia groups. k _2MIBI and k _2TF were significantly (P < 0.05) lower than k _2TL and increased significantly (P < 0.05) in the severe ischemia group (k _2TF 0.0056 ± 0.0022, 0.0037 ± 0.0015, and 0.024 ± 0.015; and k _2MIBI 0.00072 ± 0.0011, 0.00038 ± 0.00076, and 0.042 ± 0.034). k _2MIBI was significantly (P < 0.05) lower than k _2TF in the normal control and mild ischemia groups. Conclusions Tracer extraction was higher for TL than for the ^99mTc tracers and all tracers decreased according to the severity of ischemia–reperfusion in the three tracer groups. The clearance kinetics of not only MIBI but also TF is possibly useful for the evaluation of the severity of ischemia, and the Langendorff method and a methodological approach by continuous determinations of radioactivity may serve for the quantitative analysis of tracer kinetic profiles.     

Dopamine transporter SPECT using fast kinetic ligands: <Superscript>123</Superscript>I-FP-β-CIT versus <Superscript>99m</Superscript>Tc-TRODAT-1

A comparative study was carried out on two promising presynaptic dopamine transporter single-photon emission tomography (SPECT) radioligands with a fast pharmacokinetic profile, ¹²³I-FP--CIT (FP) and ^99mTc-TRODAT-1 (TR), in order to assess their differential diagnostic power in early parkinsonism and their sensitivity for detection of disease progression. This cross-sectional study was conducted on 96 patients with early-stage parkinsonism referred in a tertiary clinical setting. Mean disease duration was 2.0±1.3 years, and patients had a modified Hoehn and Yahr (H&Y) stage of 1–2 (average 1.2). Forty-seven patients received TR, and 49 received FP. In both groups, ten patients with normal presynaptic function were included as a control population; all other patients were clinically diagnosed as having idiopathic Parkinsons disease. Groups were matched for gender, age, disease duration and modified H&Y stage. Triple-head gamma camera SPECT was analysed using a semiquantitative index of transporter binding (BI). Discriminant analysis with cross-validation resulted in a maximal classification accuracy for FP of 93% (sensitivity 95% and specificity 86%) for the contralateral putamen BI. For TR, the corresponding values were 87% accuracy, 92% sensitivity and 70% specificity. For FP, disease duration was correlated with both the putamen BI (–8.8%/year, =–0.41, P=0.025) and the putamen/caudate ratio (–7.4%/year, =–0.51, P=0.004), but for TR no significant correlation was found (all P values >0.5). In conclusion, both FP and TR show high sensitivity in a clinically relevant setting, but FP has superior accuracy for early differential diagnosis of idiopathic parkinsonism and non-degenerative extrapyramidal disorders, as well as better sensitivity for disease follow-up.     

<Superscript>18</Superscript>p-FDG PET is superior to<Superscript>67</Superscript>Ga SPECT in the staging of non-Hodgkin’s lymphoma

OBJECTIVE: Our study aims to compare diagnostic accuracy between 18F-FDG PET and 67Ga SPECT in the staging of non-Hodgkin's lymphoma. METHODS: Twenty-eight patients with non-Hodgkin's lymphoma, underwent 18F-FDG PET, 67Ga SPECT and CT for the pretreatment staging of malignant lymphoma between August 1999 and March 2002. 18F-FDG PET imaging was obtained 60 minutes after the intravenous administration of 185 MBq of 18F-FDG. 67Ga SPECT imaging was obtained 2 days after the intravenous administration of 148 MBq of 67Ga. 18F-FDG PET and 67Ga SPECT were performed within one month. Both imagings were performed on the area from the neck to the pelvis. The 18F-FDG PET and 67Ga SPECT findings were compared with the CT findings and the clinical course. RESULTS: Sixty-six nodal lesions were clinically confirmed. Of these, 32 were identified by both 18F-FDG PET and 67Ga SPECT. The remaining 34 lesions were identified only by 18F-FDG PET. The mean (+/- SD) sizes' of the nodes were 34.7 +/- 32.4 mm for 18F-FDG-positive and 67Ga-positive lesions and 15.7 +/- 8.3 mm for 18F-FDG-positive and 67Ga-negative lesions (p < 0.001). Of the 23 extranodal lesions, 12 were identified by both 18F-FDG PET and 67Ga SPECT, whereas 6 lesions were identified by only 18F-FDG PET. Five lesions were not identified by either technique. No 18F-FDG-negative but 67Ga-positive nodal or extranodal lesions were observed. The difference in findings between the two studies is related to the difference in the size but not in the histology or site of the lesions. CONCLUSION: 18F-FDG PET detected significantly more lesions particularly small lesions than 67Ga SPECT. Thus, 18F-FDG PET is considered to be superior to 67Ga SPECT in the staging of non-Hodgkin' s lymphoma.     

<Superscript>125</Superscript>I brachytherapy in younger prostate cancer patients

Purpose

To evaluate local recurrence in younger men treated with low-dose-rate (LDR) ¹²⁵I brachytherapy (BT) for localized prostate cancer.

Patients and methods

A total of 192 patients (≤65-years-old) were treated with LDR ¹²⁵I-BT ± hormone therapy. Local failure was defined as any prostate-specific antigen (PSA) rise leading to salvage treatment or biochemical failure according to the Phoenix definition. A bounce was defined as a rise in the nadir of ≥0.2?ng/mL followed by spontaneous return. Proportions were compared using Fisher’s exact tests; continuous variables using the unpaired t-test or its non-parametric equivalent. Cox proportional hazards models were applied for multivariable survival analysis.

Results

Median follow-up was 66 months. The 5?year local recurrence-free survival was 96.1%. Biopsy-proven local recurrence developed in 13 patients, 4 had a Phoenix-defined recurrence at the last follow-up. Androgen deprivation therapy was started in 1 patient without proven recurrence. Univariable risk factors for local recurrence were: at least 50% positive biopsies, intermediate risk, treatment with neoadjuvant hormone therapy, low preimplantation volume receiving 100% of the prescribed dose, and no bounce development. Hormone-naïve patients not attaining a PSA value <0.5?ng/mL during follow-up also had a higher risk of local recurrences. Cox regression demonstrated that the variables “at least 50% positive biopsies” and “bounce” significantly impacted local failure (hazard ratio, HR 1.02 and 11.59, respectively). A bounce developed in 70 patients (36%). Younger patients and those treated with a lower activity per volume had a higher chance of developing a bounce in the Cox model (HR 0.99 and 0.04, respectively).

Conclusion

For younger men, LDR BT is a valid primary curative treatment option in low-risk and is to consider in intermediate-risk localized prostate cancer.

     

<Superscript>18</Superscript>F-labeled mini-PEG spacered RGD dimer (<Superscript>18</Superscript>F-FPRGD2): synthesis and microPET imaging of α<Subscript>v</Subscript>β<Subscript>3</Subscript> integrin expression

Purpose We have previously reported that ¹⁸F-FB-E[c(RGDyK)]₂ (¹⁸F-FRGD2) allows quantitative PET imaging of integrin α_vβ₃ expression. However, the potential clinical translation was hampered by the relatively low radiochemical yield. The goal of this study was to improve the radiolabeling yield, without compromising the tumor targeting efficiency and in vivo kinetics, by incorporating a hydrophilic bifunctional mini-PEG spacer. Methods ¹⁸F-FB-mini-PEG-E[c(RGDyK)]₂ (¹⁸F-FPRGD2) was synthesized by coupling N-succinimidyl-4-¹⁸F-fluorobenzoate (¹⁸F-SFB) with NH₂-mini-PEG-E[c(RGDyK)]₂ (denoted as PRGD2). In vitro receptor binding affinity, metabolic stability, and integrin α_vβ₃ specificity of the new tracer ¹⁸F-FPRGD2 were assessed. The diagnostic value of ¹⁸F-FPRGD2 was evaluated in subcutaneous U87MG glioblastoma xenografted mice and in c-neu transgenic mice by quantitative microPET imaging studies. Results The decay-corrected radiochemical yield based on ¹⁸F-SFB was more than 60% with radiochemical purity of >99%. ¹⁸F-FPRGD2 had high receptor binding affinity, metabolic stability, and integrin α_vβ₃-specific tumor uptake in the U87MG glioma xenograft model comparable to those of ¹⁸F-FRGD2. The kidney uptake was appreciably lower for ¹⁸F-FPRGD2 compared with ¹⁸F-FRGD2 [2.0 ± 0.2%ID/g for ¹⁸F-FPRGD2 vs 3.0 ± 0.2%ID/g for ¹⁸F-FRGD2 at 1 h post injection (p.i.)]. The uptake in all the other organs except the urinary bladder was at background level. ¹⁸F-FPRGD2 also exhibited excellent tumor uptake in c-neu oncomice (3.6 ± 0.1%ID/g at 30 min p.i.). Conclusion Incorporation of a mini-PEG spacer significantly improved the overall radiolabeling yield of ¹⁸F-FPRGD2. ¹⁸F-FPRGD2 also had reduced renal uptake and similar tumor targeting efficacy as compared with ¹⁸F-FRGD2. Further testing and clinical translation of ¹⁸F-FPRGD2 are warranted. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Zhanhong Wu and Zi-Bo Li contributed equally to this work.     

Comparison of <Superscript>99m</Superscript>Tc-annexin A5 with <Superscript>18</Superscript>F-FDG for the detection of atherosclerosis in ApoE−/− mice

Purpose ^99mTc-annexin A5, a marker of ongoing apoptosis, and ¹⁸F-FDG, a marker of the increased metabolism of inflammatory cells, are supposed to be useful in the detection of metabolically active atheroma. This study reports a comparison of the intralesional distribution of these tracers in relation to lesion development in ApoE−/− mice. Methods Male ApoE−/− mice (n = 12–14/group) were maintained on a Western-type diet after the age of 5 weeks. At 25 weeks, ^99mTc-annexin A5 or ¹⁸F-FDG was injected and the aortas were harvested for autoradiography (ARG) and Oil Red O staining. Regional radioactivity accumulation was compared in relation to the Oil Red O staining score (ranging from 0 to 3, a semiquantitative parameter for evaluating lesion development). Results Both ^99mTc-annexin A5 and ¹⁸F-FDG showed preferential uptake into atherosclerotic lesions, with higher uptake levels for ¹⁸F-FDG (mean, 56.07 %ID×kg/m²) than for ^99mTc-annexin A5 (mean, 10.38 %ID×kg/m²). The regional uptake levels of each tracer correlated with the Oil Red O staining score (r = 0.65, p < 0.05 for ^99mTc-annexin A5; r = 0.56, p < 0.05 for ¹⁸F-FDG). The uptake ratios of advanced lesions (score >0.5) to early lesions (score <0.5) were significantly higher for ^99mTc-annexin A5 than for ¹⁸F-FDG (f = 4.73, p = 0.03). Conclusion Both ^99mTc-annexin A5 and ¹⁸F-FDG accumulate in atherosclerotic lesions and correlate with the severity of each lesion. The higher absolute uptake levels of ¹⁸F-FDG may be advantageous for lesion detection, whereas the preferential uptake of ^99mTc-annexin A5 in advanced lesions may be a useful indicator of late-stage lesions or vulnerable plaque transformation.     

<Superscript>68</Superscript>Ga-DOTATATE PET–CT imaging in carotid body paragangliomas

Objective

The aim of this study was to present our experience in the baseline evaluation of carotid body paragangliomas (CBP) with ⁶⁸Ga-DOTATATE PET–CT.

Methods

Five patients (4F, 1M; age 24–73 years) with CBPs who underwent ⁶⁸Ga-DOTATATE PET–CT scan before the treatment were evaluated retrospectively. PET–CT images were analyzed visually as well as semiquantitatively, with measurement of maximum standardized uptake value (SUV_max).

Results

All patients had unilateral CBP lesion, showed intense ⁶⁸Ga-DOTATATE uptake in PET–CT. Additionally, ⁶⁸Ga-DOTATATE avid lesions were found in two patients. One of them had focal intense uptake in thyroid gland and frontal cerebrum. The other one had intense uptake in bone and adrenal mass. Four patients were operated for unilateral primary CBP. Last patient was treated with peptide receptor radionuclide therapy (¹⁷⁷Lu-DOTATATE) for both metastatic pheochromocytoma and CBP.

Conclusions

⁶⁸Ga-DOTATATE PET–CT is a valuable imaging modality for staging of CBPs, detecting unknown lesions and changing the management of patients. It is also useful in demonstrating expression of SSTRs for PRRT opportunity.

     

MRI and <Superscript>1</Superscript>H MRS findings in Smith-Lemli-Opitz syndrome

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder characterized by a defect in cholesterol biosynthesis, associated with mental retardation and multisystem structural abnormalities. This study investigated the prevalence of congenital CNS abnormalities by MRI in a large series of patients with SLOS and the correlation of the clinical and biochemical findings with the results of MRI and ¹H MRS. Eighteen patients were studied; all underwent MRI of the brain, and 16 had ¹H MRS of the cerebral white matter. The ratios choline:NAA, lipid:NAA, and lipid:choline metabolite were found to be correlated with the clinical degree of disease severity, serum total sterol ratios (cholesterol/cholesterol + 7-dehydrocholesterol + 8-dehydrocholesterol) and in two cases with the effect of cholesterol therapy. Abnormal CNS findings were noted in five patients, including callosal abnormalities (n=4), Dandy-Walker variant (n=1), and arachnoid cyst (n=1). Holoprosencephaly was noted in one patient with a prevalence of 6%. Choline:NAA was elevated in seven patients. There was a statistically significant positive correlation between the lipid:choline ratio and the serum cholesterol precursor, 8-dehydrocholesterol. In two patients ¹H MRS demonstrated abnormally elevated lipids prior to cholesterol therapy, which improved on therapy. The use of MRI and ¹H MRS is an effective way to demonstrate brain structural abnormalities in patients with SLOS and may prove to be an effective method for the assessment of the effects of cholesterol replacement therapy in the brain.     

PET imaging of α<Subscript>7</Subscript> nicotinic acetylcholine receptors: a comparative study of [<Superscript>18</Superscript>F]ASEM and [<Superscript>18</Superscript>F]DBT-10 in nonhuman primates,and further evaluation of [<Superscript>18</Superscript>F]ASEM in humans

Purpose

The α₇ nicotinic acetylcholine receptor (nAChR) is implicated in many neuropsychiatric disorders, making it an important target for positron emission tomography (PET) imaging. The first aim of this work was to compare two α₇ nAChRs PET radioligands, [¹⁸F]ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-([¹⁸F]fluorodibenzo[b,d]thiophene 5,5-dioxide) and [¹⁸F]DBT-10 (7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-([¹⁸F]fluorodibenzo[b,d]thiophene 5,5-dioxide), in nonhuman primates. The second aim was to assess further the quantification and test-retest variability of [¹⁸F]ASEM in humans.

Methods

PET scans with high specific activity [¹⁸F]ASEM or [¹⁸F]DBT-10 were acquired in three rhesus monkeys (one male, two female), and the kinetic properties of these radiotracers were compared. Additional [¹⁸F]ASEM PET scans with blocking doses of nicotine, varenicline, and cold ASEM were acquired separately in two animals. Next, six human subjects (five male, one female) were imaged with [¹⁸F]ASEM PET for 180 min, and arterial sampling was used to measure the parent input function. Different modeling approaches were compared to identify the optimal analysis method and scan duration for quantification of [¹⁸F]ASEM distribution volume (V _T). In addition, retest scans were acquired in four subjects (three male, one female), and the test-retest variability of V _T was assessed.

Results

In the rhesus monkey brain [¹⁸F]ASEM and [¹⁸F]DBT-10 exhibited highly similar kinetic profiles. Dose-dependent blockade of [¹⁸F]ASEM binding was observed, while administration of either nicotine or varenicline did not change [¹⁸F]ASEM V _T. [¹⁸F]ASEM was selected for further validation because it has been used in humans. Accurate quantification of [¹⁸F]ASEM V _T in humans was achieved using multilinear analysis with at least 90 min of data acquisition, resulting in V _T values ranging from 19.6?±?2.5 mL/cm³ in cerebellum to 25.9?±?2.9 mL/cm³ in thalamus. Test-retest variability of V _T was 11.7?±?9.8%.

Conclusions

These results confirm [¹⁸F]ASEM as a suitable radiotracer for the imaging and quantification of α₇ nAChRs in humans.

     

Intra-individual comparison of p-[<Superscript>123</Superscript>I]-iodo-L-phenylalanine and L-3-[<Superscript>123</Superscript>I]-iodo-α-methyl-tyrosine for SPECT imaging of gliomas

Objectives Radioactive amino-acids accumulate in gliomas even with an intact blood-brain-barrier. L-3-[¹²³I]-iodo-α-methyl-tyrosine (IMT) is well established for SPECT imaging of gliomas. Recently, we introduced p-[¹²³I]-iodo-L-phenylalanine (IPA) for the characterisation of brain lesions. This study compares both tracers in glioma patients. Methods Eleven patients with gliomas (1 WHO grade 1, 5 grade 2, 1 grade 3, 2 grade 4 gliomas, 1 unconfirmed upgrading and 1 post-therapeutic non-neoplastic lesion) underwent SPECT imaging with IPA (early and delayed acquisitions at 30 min and 3 h) and IMT (early only). Maximum tumour-to-brain ratios (TBR) were calculated using region-of-interest analysis to assess uptake of IMT and IPA. Imaging results were compared to histopathological findings. Results Early TBRs of IMT and IPA were strongly correlated (r = 0.828, p = 0.002). TBRs were higher for IMT than IPA (1.95±0.50 versus 1.79±0.42; p < 0.05), but independent from tumour cell density (p > 0.1). Visual interpretation by different observers was more concordant for IMT-SPECT than IPA-SPECT (kappa 1.0 versus 0.774). No differences in early TBRs were observed between low-grade and high-grade gliomas for IMT (1.97±0.53 versus 2.21±0.44, p > 0.5) or IPA (1.70±0.23 versus 2.21±0.56, p = 0.167) with a trend to higher TBRs in low-grade tumours for IMT (p = 0.093). In contrast to the known wash-out of IMT, we observed persistent accumulation of IPA in gliomas. Conclusions IPA shows lower TBRs than IMT, especially in low-grade tumours, so IMT should be preferred for the delineation of low-grade gliomas by SPECT imaging. Due to its prolonged retention, however, IPA remains promising for therapeutic use in gliomas after labelling with I-131. This work was supported by a grant from the “Deutsche Krebshilfe” (70-3024-He 1).