No abstract available

No abstract available

[en] Short communication

[en] The majority of pheochromocytomas and paragangliomas are benign, with malignancy occurring in approximately 10% of pheochromocytoma patients. The malignancy rate among paragangliomas is 15-35% or higher if associated with succinate dehydrogenase B gene mutations. The 5-year mortality rate in malignant pheochromocytoma and paraganglioma is nearly 50%. Malignancy of both pheochromocytoma and paraganglioma is determined by the existence of metastasis or local invasion and not by the cellular characteristics. There are no known clinical, biochemical or histopathological differences between pheochromocytoma and paraganglioma. Metaiodobenzylguanidine (MIBG) radiolabeled with either ¹²³I or ¹³¹I has been used to diagnose neuroendocrine tumors such as paraganglioma and pheochromocytoma, and ¹³¹I-MIBG has been used to treat these tumors. The role of radioiodinated MIBG in treating neuroendocrine tumors is still being evaluated. More recently, no-carrier-added (nca) MIBG has become available, and the advantages of nca MIBG over ca MIBG are being demonstrated. This article reviews the biology of paragangliomas and pheochromocytomas, the role of MIBG imaging in the diagnosis of these tumors and the role of both ca and nca ¹³¹I-MIBG in the treatment of these tumors. New data on nca ¹³¹I-MIBG in the therapy of these tumors are included

[en] Introduction: In recent years extra-corporal application of boron neutron capture therapy (BNCT) was evaluated for liver primary tumors or liver metastases. A prerequisite for such a high-risk procedure is proof of preferential delivery and high uptake of a ¹⁰B-pharmaceutical in liver malignancies. In this work we evaluated in a preclinical tumor model if [¹⁸F]FBPA tissue distribution measured with PET is able to predict the tissue distribution of [¹⁰B]L-BPA. Methods: Tumor bearing mice (hepatocellular carcinoma cell line, HuH-7) were either subject of a [¹⁸F]FBPA-PET scan with subsequent measurement of radioactivity content in extracted organs using a gamma counter or injected with [¹⁰B]L-BPA with tissue samples analyzed by prompt gamma activation analysis (PGAA) or quantitative neutron capture radiography (QNCR). The impact of L-tyrosine, L-DOPA and L-BPA preloading on the tissue distribution of [¹⁸F]FBPA and [¹⁰B]L-BPA was evaluated and the pharmacokinetics of [¹⁸F]FBPA investigated by compartment modeling. Results: We found a significant correlation between [¹⁸F]FBPA and [¹⁰B]L-BPA uptake in tumors and various organs as well as high accumulation levels in pancreas and kidneys as reported in previous studies. Tumor-to-liver ratios of [¹⁸F]FBPA ranged from 1.2 to 1.5. Preloading did not increase the uptake of [¹⁸F]FBPA or [¹⁰B]L-BPA in any organ and compartment modeling showed no statistically significant differences in [¹⁸F]FBPA tumor kinetics. Conclusions: [¹⁸F]FBPA-PET predicts [¹⁰B]L-BPA concentration after amino acid preloading in HuH-7 hepatocellular carcinoma models. Preloading had no effect on tumor uptake of [¹⁸F]FBPA. Advances in knowledge: Despite differences in chemical structure and administered dose [¹⁸F]FBPA and [¹⁰B]L-BPA demonstrate an equivalent biodistribution in a preclinical tumor model. Implications for patient care: [¹⁸F]FBPA-PET is suitable for treatment planning and dose calculations in BNCT applications for liver malignancies. However, alternative tracers with more favorable tumor-to-liver ratios should be investigated.

[en] Introduction: Peripheral artery disease can lead to severe disability and limb loss. Therapeutic strategies focussing on macrovascular repair have shown benefit but have not significantly reduced amputation rates in progressive PAD. Proangiogenic small molecule therapies may substantially improve vascularisation in limb ischemia. The purpose of the current study was to assess the proangiogenic effects of simvastatin in a murine model of hind limb ischemia using longitudinal multimodal imaging. Methods: Mice underwent surgical intervention to induce hind limb ischemia, and were treated with simvastatin orally for 28 days. Neovascularisation was assessed using ^99mTc-RGD SPECT imaging, and macrovascular volume was assessed by quantitative time of flight MRI. At each imaging time point, VEGF expression and capillary vessel density were quantified using immunohistochemical analysis. Results: Simvastatin significantly increased ^99mTc-RGD retention in the ischemic hind limb by day 3 post-surgery, with maximal retention at day 8. Vascular volume was significantly increased in the ischemic hind limb of simvastatin treated animals, but only by day 22. Immunohistochemical analysis shows that simvastatin significantly augmented tissue VEGF expression from day 8 with increase in capillary density (CD31⁺) from day 14. Conclusions: Early assessment of proangiogenic therapy efficacy can be identified using ^99mTc-RGD SPECT, which displays significant increases in retention before macrovascular volume changes are measureable with MRI. Advances in knowledge and implications for patient care: Simvastatin offers an effective proangiogenic therapy as an adjunct for management of limb ischemia. Simvastatin induces integrin expression and vascular remodeling leading to neovascularisation and improved perfusion.

[en] Introduction: Technetium-99m-hexamethylpropyleneamine oxime (^99mTc-HMPAO) is potentially useful for the assessment of cerebral blood flow (CBF) in small animals. In this paper, a procedure for quantitation of rat CBF using ^99mTc-HMPAO was determined. Methods: Biodistribution of ^99mTc-radioactivity in normal rats was determined after intravenous administration of ^99mTc-HMPAO. Acetazolamide treated rats were intravenously administered with the mixture of ^99mTc-HMPAO and N-isopropyl-[¹²⁵I]iodoamphetamine ([¹²⁵I]IMP), and arterial blood was then collected for 5 min. After blood sampling, the brain radioactivity concentration was measured with the auto-well γ counter. Results: The brain radioactivity concentration after intravenous administration of ^99mTc-HMPAO was steady from 14 s to 60 min post-injection. A double tracer experiment using ^99mTc-HMPAO and [¹²⁵I]IMP showed that 19 s was the average of the optimal integration interval of arterial blood ^99mTc-radioactivity concentration to obtain CBF values measured by ^99mTc-HMPAO identical to those determined by [¹²⁵I]IMP. The CBF value determined by ^99mTc-HMPAO, calculated by dividing the brain radioactivity concentration at 5 min post-injection by the integrated arterial blood radioactivity concentration until 19 s post-injection, was well correlated with CBF as determined by [¹²⁵I]IMP. Conclusion: These results suggest that the CBF quantitation procedure described in this paper could be useful for rat CBF assessment.

[en] Background: Prostate-specific membrane antigen (PSMA) is highly over-expressed in advanced prostate cancers. ⁶⁸Ga-labeled PSMA inhibitors (iPSMA) are currently used for prostate cancer detection by PET imaging. The availability of simple, efficient and reproducible radiolabeling procedures is essential for developing new SPECT radiopharmaceuticals for clinical translation. The aim of this research was to prepare ^99mTc-EDDA/HYNIC-Lys(Nal)-Urea-Glu (^99mTc-EDDA/HYNIC-iPSMA) obtained from lyophilized kit formulations and evaluate the in vitro and in vivo radiopharmaceutical binding to prostate cancer cells over-expressing PSMA, as well as the ^99mTc-EDDA/HYNIC-iPSMA normal biodistribution in humans and the preliminary uptake in patients with prostate cancer. Methods: ^99mTc labeling was performed by adding sodium pertechnetate solution and a 0.2 M phosphate buffer (pH 7.0) to a lyophilized formulation containing HYNIC-iPSMA, EDDA, tricine, mannitol and stannous chloride. The radiochemical purity was evaluated by reversed-phase HPLC and ITLC-SG analyses. Stability studies in human serum were performed by size-exclusion HPLC. In vitro cell uptake was tested using prostate cancer cells (LNCaP) with blocked and non-blocked receptors. Biodistribution and tumor uptake were determined in LNCaP tumor-bearing nude mice with blocked and non-blocked receptors, and images were obtained using a micro-SPECT/CT. Whole-body images from three healthy men and two patients with histologically-confirmed prostate cancer (one of them with a previous ⁶⁸Ga-PSMA-617scan) were acquired at 1 h and 3 h after ^99mTc-EDDA/HYNIC-iPSMA administration with radiochemical purities of >98%. Results: In vitro and in vivo studies showed high radiopharmaceutical stability in human serum, specific recognition for PSMA, high tumor uptake (10.22 ± 2.96% ID/g at 1 h) with rapid blood clearance and mainly kidney elimination. Preliminary images in patients demonstrated the ability of ^99mTc-EDDA/HYNIC-iPSMA to detect tumors and metastases of prostate cancer as well as ⁶⁸Ga-PSMA-617 does. Conclusions: The results obtained in this study warrant further dosimetry and clinical studies to determine the specificity and sensitivity of ^99mTc-EDDA/HYNIC-iPSMA.

[en] 2-(2-(3-(4-(2-[¹⁸F]Fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([¹⁸F]MNI-659, [¹⁸F]1) is a useful PET radiotracer for imaging phosphodiesterase 10A (PDE10A) in human brain. [¹⁸F]1 has been previously prepared by direct [¹⁸F]fluorination of a tosylate precursor 2 with [¹⁸F]F⁻. The aim of this study was to determine the conditions for the [¹⁸F]fluorination reaction to obtain [¹⁸F]1 of high quality and with sufficient radioactivity for clinical use in our institute. Moreover, we synthesized [¹⁸F]1 by [¹⁸F]fluoroethylation of a phenol precursor 3 with [¹⁸F]fluoroethyl bromide ([¹⁸F]FEtBr), and the outcomes of [¹⁸F]fluorination and [¹⁸F]fluoroethylation were compared.

[en] Performance of a second itG ⁶⁸Ge/⁶⁸Ga generator system and production of ⁶⁸Ga-DOTATOC and ⁶⁸Ga-PSMA-HBED-CC were tested over one year as an accompaniment to a previously published study (J Nucl Med. 2016;57:1402–1405).