Annals of Nuclear Medicine (v.30, #5)

Perfusion and metabolic scintigraphy with 123I-BMIPP in prognosis of cardiac resynchronization therapy in patients with dilated cardiomyopathy by Konstantin V. Zavadovsky; Marina O. Gulya; Yuri B. Lishmanov; Denis I. Lebedev (325-333).
The objective of the study was to investigate the left ventricular (LV) myocardial perfusion and metabolism in patients with idiopathic dilated cardiomyopathy (DCM) and to identify the scintigraphic predictors of the efficacy of cardiac resynchronization therapy (CRT).The study comprised 63 patients with DCM and severe heart failure (NYHA class III–IV). Before CRT, all patients received gamma-scintigraphy with 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) and with 123I-β-methyl-iodophenyl pentadecanoic acid (123I-BMIPP) for evaluation of myocardial perfusion and metabolism, respectively. Before and after 6 months of CRT, all patients underwent echocardiography study to assess cardiac hemodynamics.After 6 months of CRT, patients were divided into two groups: group 1 comprised responders in whom LV end systolic volume (LVESV) decreased by ≥15 % (n = 39); group 2 comprised non-responders in whom LVESV decreased by <15 % (n = 24). Before CRT, LV pumping function did not significantly differ between groups. Significant differences were found in the following preoperative scintigraphic parameters: myocardial perfusion defect size [7.4 % (5.9; 13.2) % and 11.8 (8.8; 16.2) %, p < 0.05] and metabolic defect size [7.4 (4.4; 14.7) % and 8.8 (8.8; 17.6) %, p < 0.05]. Metabolic scintigraphy showed greater diagnostic efficacy in determining the indications for CRT compared with perfusion scintigraphy [areas under the ROC curves (AUC) of 0.722 and 0.612, respectively]. The best metabolic defect size threshold value of 7.35 % predicted CRT efficacy with the sensitivity and specificity rates of 77.8 and 66.7 %, respectively.Data of metabolic scintigraphy may be useful for the integrated prediction of CRT efficacy.
Keywords: Dilated cardiomyopathy; Myocardial scintigraphy; Cardiac resynchronization therapy

We propose an innovative strategy of nanoparticle-mediated-peptide receptor radionuclide therapy (PRRT) employing PLGA-nanoparticles together with anti-β-hCG antibodies that can protect kidneys from radiation damage while simultaneously enhancing its tumor targeting and cytotoxic ability for somatostatin receptor (SSR) positive tumors.PEG-coated-177Lu-DOTATATE-PLGA-nanoparticles (PEG-LuD-NP) were formulated and characterized. In vitro toxicity of these particles was tested on human glioblastoma cell line U87MG over a radiation dose range of 19–78 Gy, using MTT assay and flow cytometry. To further enhance cytotoxicity and test the feasibility of active tumor targeting, apoptosis-inducing anti-β-hCG monoclonal antibodies were employed in vitro, after confirming expression of β-hCG on U87MG. In vivo tumor targeting ability of these particles, in comparison to uncoated particles and un-encapsulated 177Lu-DOTATATE, was assessed by intravenous administration in tumor-induced wistar rats. Rats were first imaged in a gamma camera followed by euthanasia for organ extraction and counting in gamma counter.The particles were spherical in shape with mean diameter of 300 nm. Highest cytotoxicity that could be achieved with PEG-LuD-NP, on radio-resistant U87MG cells, was 35.8 % due to complex cellular response triggered by ionizing radiation. Interestingly, synergistic action of antibodies and PEG-LuD-NP doubled the cytotoxicity (80 %). PEG-LuD-NP showed the highest tumor uptake (4.3 ± 0.46 % ID/g) as compared to 177Lu-DOTATATE (3.5 ± 0.31 %) and uncoated-177Lu-DOTATATE-nanoparticles (3.4 ± 0.35 %) in tumor-inoculated wistar rats (p < 0.001). Renal uptake/retention was decreased 3–4 folds with these particles, resulting in the highest tumor-to-kidney ratio (8.58; p < 0.01) while tumor-to-liver and tumor-to-bone ratios were comparable to un-encapsulated-drug.Nanocarrier-mediated-PRRT is an effective way of targeting SSR positive tumors for enhanced cytoxicity and reduced renal radiation dose associated with conventional PRRT. To our knowledge of literature, this is the first study to establish in vitro and in vivo efficacy profile of nanoparticles in PRRT providing a stepping-stone for undergoing and future research endeavors in the direction of abating associated radiation concerns of radionuclide therapy and may offer a paradigm shift in PRRT strategy.
Keywords: PLGA nanoparticles; Peptide receptor radionuclide therapy; Glioblastoma multiforme; Anti-β-hCG antibodies; Nephrotoxicity; Somatostatin receptor positive tumors

Exact classifying between malignant and benign tumors in the parotid gland is important because the cancer has relatively poor prognosis. There have been several studies that F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) can differentiate between malignant and benign parotid gland tumors. However, the role of FDG PET is still controversial because many benign parotid gland tumors, such as Warthin’s tumor and pleomorphic adenoma, show high FDG uptake. We hypothesized that metabolic heterogeneity would differentiate malignant parotid tumors because tumoral heterogeneity is an important characteristic in the malignancies.From January 2010 to April 2015, we retrospectively reviewed the 46 patients who showed FDG uptake at the parotid gland. To differentiate malignant parotid gland tumors, we obtained maximum SUV and mean SUV. Metabolic tumor volume and total lesion glycolysis were measured as metabolic volumetric parameters. We also included heterogeneity parameters of FDG PET such as heterogeneity factor (HF) and the coefficient of variation for all patients.There was significant difference of HF between malignant (−0.30 ± 0.25; range −0.937 to −0.084) and benign parotid gland tumors (−0.06 ± 0.05; range −0.291 to −0.012; p < 0.0001). In receiver operating characteristic analysis, when ≤−0.084 was used as the cut-off value for HF, the sensitivity and specificity were 100 % (95 % CI 81.5–100) and 89.2 % (95 % CI 71.8–97.7), respectively. HF showed the highest area under the curve of 0.947 among the parameters. In logistic regression analysis, the HF was the most powerful factor for differentiation of the parotid gland tumors (p = 0.002).Our results suggest that HF can be utilized as a reliable and non-invasive method for differentiation of malignant and benign parotid gland tumors.
Keywords: Parotid gland tumor; FDG PET; Heterogeneity

This study aimed to visually and quantitatively compare 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) imaging in determining postoperative pelvic recurrence in colorectal cancer (CRC).This retrospective analysis focused on 96 patients (age: mean 62.6 ± 10.5) with surgically resected CRC (time interval after surgery: 19.2 ± 20.4 months). The standard of reference was histopathologic confirmation (n = 27) or imaging follow-up (n = 69). For visual analysis, three independent nuclear physicians interpreted the PET/CT findings. For the quantitative analysis, the normalized standardized uptake values (nSUVs: nSUVmax, nSUVpeak, nSUVmean) were calculated by applying the mean SUV of a normal liver. We evaluated the areas under the receiver operating characteristic curves (AUCs) for all the quantitative parameters.Of the 96 patients, 49 showed pelvic recurrence and 47 revealed no tumor recurrence. Sensitivity and specificity were 85.7 and 80.9 %, respectively, for visual analysis, and 65.3 and 83.0 %, respectively, for quantitative analysis. The AUC (0.766, CI: 0.668–0.846) of nSUVmax was largest comparing nSUVpeak and nSUVmean values, without significant difference (p value >0.316). Sensitivity of lesion detection was superior in visual analysis (p value = 0.02), but specificity was not significantly different (p = 0.80). After inclusive and exclusive combinations, sensitivity and specificity were slightly increased to 89.8 % (p = 0.54) and 91.5 % (p = 0.14), respectively.Visual interpretation was superior to quantitative analysis in pelvic tumor recurrence in CRC. Though it was possible to improve diagnostic performance through combinatory analysis, the effect was not statistically significant.
Keywords: Colorectal cancer; Locoregional neoplasm recurrence; Pelvic region; 18F-FDG PET/CT

Prognostic value of pre-operative glucose-corrected maximum standardized uptake value in patients with non-small cell lung cancer after complete surgical resection and 5-year follow-up by Renske Konings; Matthijs H. van Gool; Martin P. L. Bard; Anthonie Zwijnenburg; Bart M. Titulaer; Tjeerd S. Aukema; Renato A. Valdés Olmos; Karolina Sikorska; Houke M. Klomp; Herman Rijna (362-368).
In this study we evaluated the value of pre-operative glucose corrected maximum standard uptake value (GC-SUVmax) as prognostic factor in patients with early stage non-small cell lung cancer (NSCLC) after complete surgical resection.This study was designed as a retrospectively evaluated single center study with prospective data registry. Inclusion criteria were: histologically proven stage I NSCLC, 18F-FDG-PET/CT scan prior to surgery, complete resection (R0) and follow up in our outpatient department. Exclusion criteria were: history of malignancy other than NSCLC, diabetes and (neo) adjuvant therapy. Follow up period was 5 years.Between 2006 and 2008 a total of 33 patients (16 males, 17 females) met the inclusion criteria. SUVmax and GC-SUVmax were strongly correlated (Spearman’s ρ = 0.97). Five-year overall survival (OS) rate was 70 % (95 % CI = 56–87 %). Patients who died within 5 years of follow up had significantly higher pre-operative GC-SUVmax (median = 10.6, IQR = 8.3–14.4) than patients who were alive at 5-year follow up (median = 6.4, IQR = 3.0–9.8), p = 0.04. SUVmax showed similar differences: 10.4 (8–12.9) vs. 6.6 (3.0–8.8), p = 0.047. The area under the receiver-operating characteristic (ROC) curve at 5 years was 0.70 (95 % CI = 0.50–0.90) for GC-SUVmax and 0.71 (95 % CI = 0.51–0.91) for SUVmax (p = 0.75).Pre-operative FDG tumor uptake in patients with NSCLC is predictive for survival after complete surgical resection. GC-SUVmax, as an additional value to SUVmax, may better approach competitive inhibition of FDG and glucose in tumors, however, in this study this potential advantage, if any, was very small.
Keywords: PET/CT; Prognostic; Non-small cell lung cancer; Surgery; Early stage

Preclinical evaluation of isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu for folate receptor-positive tumor targeting by Woo Hyoung Kim; Chang Guhn Kim; Myoung Hyoun Kim; Dae-Weung Kim; Cho Rong Park; Ji Yong Park; Yun-Sang Lee; Hyewon Youn; Keon Wook Kang; Jae Min Jeong; June-Key Chung (369-379).
The purpose of the present study was to prepare isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu (folate-GGCE), and to evaluate the feasibility of their use for folate receptor (FR)-targeted molecular imaging and as theranostic agents in a mouse tumor model.Folate-GGCE was synthesized using solid-phase peptide synthesis and radiolabeled with Tc-99m or Re-188. Radiochemical characterization was performed by radio-high-performance liquid chromatography. The biodistribution of Tc-99m-folate-GGCE was studied, with or without co-injection of excess free folate, in mice bearing both FR-positive (KB cell) and FR-negative (HT1080 cell) tumors. Biodistribution of Re-188-folate-GGCE was studied in mice bearing KB tumors. Serial planar scintigraphy was performed in the dual tumor mouse model after intravenous injection of Tc-99m-folate-GGCE. Serial micro-single photon emission computed tomography/computed tomography (SPECT/CT) studies were performed, with or without co-injection of excess free folate, in the mouse tumor model after injection of Tc-99m-folate-GGCE or Re-188-folate-GGCE.The radiolabeling efficiency and radiochemical stability of Tc-99m- and Re-188-folate-GGCE were more than 95 % for up to 4 h after radiolabeling. Uptake of Tc-99m-folate-GGCE at 1, 2, and 4 h after injection in KB tumor was 16.4, 23.2, and 17.6 % injected dose per gram (%ID/g), respectively. This uptake was suppressed by 97.4 % when excess free folate was co-administered. Tumor:normal organ ratios at 4 h for blood, liver, lung, muscle, and kidney were 54.3, 25.2, 38.3, 97.8, and 0.3, respectively. Tumor uptake of Re-188-folate-GGCE at 2, 4, 8, and 16 h after injection was 17.4, 21.7, 24.1, and 15.6 %ID/g, respectively. Tumor:normal organ ratios at 8 h for blood, liver, lung, muscle, and kidney were 126.8, 21.9, 54.8, 80.3, and 0.4, respectively. KB tumors were clearly visualized at a high intensity using serial scintigraphy and micro-SPECT/CT in mice injected with Tc-99m- or Re-188-folate-GGCE. The tumor uptake of these molecules was completely suppressed when excess free folate was co-administered.Isostructural Tc-99m- and Re-188-folate-GGCE showed high and FR-specific uptake by tumors and generally favorable tumor:normal organ ratios. The tumor targeting capabilities of Tc-99m- and Re-188-folate-GGCE were clearly evident on serial imaging studies. This isostructural pair may have potential diagnostic and theranostic applications for FR-positive tumors.
Keywords: Folate receptor; Tumor; Tc-99m; Re-188; SPECT/CT

We report a patient who set off a restroom’s ultraviolet-spectrum flame detector, occurring 2.5 h after administration of radioisotope 99mTc-MDP (740 MBq) for bone scintigraphy. The radiation dose rate emitted from the patient was estimated to be about 11.82 μSv/h at a distance of 100 cm. To date, many cases have been reported of radiation detector false alarms triggered by radioisotopes administered to patients, presumably due to strengthened security measures and increased radioisotope use. Only one other case of false flame detector triggering in relation to radioisotope administration has been reported, in that case due to therapeutic radioiodine; there have been no prior reports of diagnostic 99mTc triggering flame detectors.
Keywords: Ultraviolet flame detector; Radiation alarm; Patient information; Radiation protection certificate; 99mTechnetium-Methyl diphosphonate (99mTc-MDP)