Annals of Nuclear Medicine (v.26, #5)

Synthesis and evaluation of radioiodinated phenoxyquinazoline and benzylaminoquinazoline derivatives as new EGF receptor tyrosine kinase imaging ligands for tumor diagnosis using SPECT by Masahiko Hirata; Yasukazu Kanai; Sadahiro Naka; Keiji Matsumuro; Shinya Kagawa; Mitsuyoshi Yoshimoto; Yoshiro Ohmomo (381-389).
Epidermal growth factor receptor tyrosine kinase (EGFR-TK) represents an attractive target for tumor diagnosis agents. Previously, the radioiodinated 4-(3-iodoanilino)-6,7-diethoxyquinazoline ([125I]m-IPQ) has been reported to possess good characteristics as a tumor imaging agent; however, it was also found to have low in vivo stability. To improve the in vivo stability, m-IPQ derivatives, 4-(3-iodophenoxy)-6,7-diethoxyquinazoline (PHY) and 4-(3-iodobenzylamino)-6,7-diethoxyquinazoline (BAY) were designed and synthesized, and the biological studies of [125I]PHY and [125I]BAY were performed to evaluate these new ligands as in vivo tumor diagnosis agents.PHY and BAY were synthesized according to previous reports. The EGFR-TK inhibitory potency of these new compounds was measured and compared to other EGFR-TK inhibitors. Radiolabeled [125I]PHY and [125I]BAY were synthesized by an iododestannylation reaction. Biodistribution studies of these radioligands were conducted in normal mice and tumor-bearing mice. Furthermore, selectivity and binding characteristics of [125I]PHY were analyzed by in vitro blocking studies and a binding assay.The new derivatives were found to have high inhibitory potency against EGFR-TK (PHY: IC50 = 12.7 ± 7.2 nM, BAY: IC50 = 51.0 ± 8.9 nM). [125I]PHY and [125I]BAY were conveniently synthesized from tributylstannyl precursors. In in vivo biodistribution studies, [125I]PHY and [125I]BAY were observed to have lower uptake in the stomach, an indication of deiodination, than [125I]m-IPQ. Moreover, [125I]PHY showed high uptake and prolonged retention in tumors and low accumulation in blood and muscle tissue resulting in a good tumor-to-blood ratio (0.94–1.50) and tumor-to-muscle ratio (1.02–1.95). The EGFR-TK selectivity of [125I]PHY was confirmed by pretreatment experiments with specific EGFR-TK inhibitors.New radioiodinated quinazoline derivatives were synthesized, which were found to have improved in vivo stability. In particular, [125I]PHY showed higher tumor accumulation than the other ligands which was indicative of selective binding to EGFR-TK. These desirable characteristics for [125I]PHY suggest that the 123I-labeled counterpart, [123I]PHY, could be a possible candidate for cancer diagnosis radiopharmaceutical.
Keywords: EGF; Radiopharmaceutical; SPECT; Tyrosine kinase; PD153035

To evaluate for how long patients should be isolated after I-131 treatment for thyroid cancer according to the guidelines issued by the Japanese Ministry of Welfare.We reviewed 92 therapies performed in 76 patients who were administered I-131 at our hospital from July 2007 to September 2009. Fifty-six patients were given 2220 or 2960 MBq I-131 at the first therapy, and 29 patients underwent 36 repeated therapies using 2960, 3700, 5550 or 7400 MBq I-131. We surveyed radioactivity for a 1 cm dose equivalent rate at 1 m intervals at 30 and 48 h after administration of I-131, obtained planar scintigrams at 48 h, and surveyed radioactivity repeatedly until it fell to under 30 μSv/h.The radioactivity was under 30 μSv/h at 30 h in 51 out of 92 cases (55%). Among the remaining 41 (45%) cases, 27 (29%) and 32 (35%) cases showed decreased radioactivity under 30 μSv/h at 48 and 72 h, respectively, and it remained higher than 30 μSv/h at 72 h in another 9 cases (10%). In 5 (38%) of the 13 cases with bone metastasis, the radioactivity remained over 30 μSv/h after 72 h, and scintigrams showed strong accumulation in bone metastases. Among the 27 cases demonstrating below 30 μSv/h at 48 h, 26 showed radioactivity being below 50 μSv/h at 30 h, while it was above 50 μSv/h at 30 h in all 14 cases which demonstrated above 30 μSv/h at 48 h. We compared the radioactivity levels of 27 cases under 30 μSv/h at 48 h and 14 cases over 30 μSv/h at 48 h using a cutoff value of under 50 μSv/h at 30 h to release patient at 48 h, the positive predictive value and negative predictive value were 100 and 93%, respectively, and radioactivity was found to differ significantly (P < 0.001).To predict external radiation levels at 48 h, it is helpful to consider external radiation levels at 30 h after treatment. Consideration of intracellular uptake in thyroid cancer, especially in cases of bone metastases, digestive tract function, and renal function, is important for predicting isolated period.
Keywords: Thyroid cancer; Radioisotope therapy; I-131; Radiation dose rate

SISCOM technique with a variable Z score improves detectability of focal cortical dysplasia: a comparative study with MRI by Yukio Kimura; Noriko Sato; Kimiteru Ito; Kouhei Kamiya; Yasuhiro Nakata; Yuko Saito; Hiroshi Matsuda; Kenji Sugai; Masayuki Sasaki; Hideharu Sugimoto (397-404).
Focal cortical dysplasia (FCD) is one of the causes of epilepsy, but its diagnosis by MRI remains difficult. The purpose of this study was to evaluate the use of subtraction ictal SPECT coregistered to MRI (SISCOM) and MRI to detect the epileptogenic focus in patients with FCD.MRI and SISCOM findings of 20 patients with pathologically proven FCD were retrospectively reviewed. MRI was visually assessed for detecting FCD. SISCOM was evaluated by a new method selecting a higher standard deviation (Z score) area as the epileptogenic focus. We scored the detectability in both SISCOM and MRI while referring to the pathology.Sixteen patients agreed with pathology on SISCOM and 14 patients on MRI. Although MRI could not point out foci in two cases of FCD type I, SISCOM could do so in both of them. A combined diagnosis of SISCOM and MRI agreed with the pathology in 18 patients.Narrowing the target by elevating the Z score on SISCOM seems to be an appropriate method to detect the foci without the need for expertise of radiologists. We recommend this combined method of SISCOM and MRI for presurgical evaluation in patients with FCD.
Keywords: Focal cortical dysplasia; SISCOM; Ictal SPECT; Epilepsy

Reevaluation of FDG-PET/CT in patients with hoarseness caused by vocal cord palsy by Ryogo Minamimoto; Kazuo Kubota; Miyako Morooka; Kimiteru Ito; Takuya Mitsumoto; Momoko Okasaki; Takuro Shimbo; Niro Tayama (405-411).
Vocal cord palsy (VCP) is a potential cause of hoarseness that results in decreasing mobility of the vocal cord. VCP can arise from a variety of causes; so, systematic screening is warranted for the management of patients with VCP. Asymmetrical fluorodeoxyglucose (FDG) uptake in vocal cords is a well-known feature in patients with VCP, but no detailed analysis has been performed. This study aimed at reevaluating the 18F-FDG positron emission tomography/computed tomography (PET/CT) for patients with VCP.We retrospectively surveyed the results of FDG-PET/CT for 59 patients with VCP, compared to laryngoscopic findings. Quantitative analysis was performed using maximum standardized uptake value (SUVmax), and regions of interest were drawn over bilateral vocal cords as confirmed from the CT portion of PET/CT. Patients were divided into 3 groups: Group 1 (n = 14), in which VCP was caused by the lesion of the laryngeal area; Group 2 (n = 40), in which VCP was caused by the lesion on the root of the recurrent laryngeal nerve; and Group 3 (n = 5), in which VCP was caused by the lesion from the vagal center to the proximal vagus nerve.For Group 1, higher FDG uptake in the paralyzed vocal cord was seen in 86 % of patients (mean SUVmax 8.1 ± 5.3 vs. 2.3 ± 0.4, paralyzed vs. non-paralyzed, respectively; P < 0.002). The sensitivity of FDG-PET/CT for indicating the lesion causing VCP was 79 % for Group 1. Group 2 showed dominant FDG uptake in the non-paralyzed vocal cord (mean SUVmax 2.1 ± 0.9 vs. 1.5 ± 0.4, non-paralyzed vs. paralyzed, respectively; P < 0.001). The sensitivity of FDG-PET/CT for indicating the lesion causing VCP was 93 % for Group 2. Group 3 showed no statistically significant difference in FDG accumulation between non-paralyzed and paralyzed vocal cords (mean SUVmax 1.8 ± 0.3 vs. 1.7 ± 0.3, non- paralyzed vs. paralyzed, respectively; P = 0.30). The sensitivity of FDG-PET/CT for indicating the lesion causing VCP was 60 % for Group 3.FDG accumulation in the vocal cords is dependent on the lesion site causing VCP. In addition, FDG-PET/CT can contribute to identification of the lesion responsible for inducing VCP.
Keywords: FDG-PET/CT; Hoarseness; Vocal cord palsy; Recurrent laryngeal nerve; Vagus nerve

Bremsstrahlung parameters of praseodymium-142 in different human tissues: a dosimetric perspective for 142Pr radionuclide therapy by Mohamadreza K. Bakht; Hamidreza Jabal-Ameli; Seyed J. Ahmadi; Mahdi Sadeghi; Sodeh Sadjadi; Claudio Tenreiro (412-418).
Praseodymium-142 [T 1/2 = 19.12 h, $$ E_{eta^{-}}$$  = 2.162 MeV (96.3%), Eγ = 1575 keV (3.7%)] is one of the 141Pr radioisotopes. Many studies have been attempted to assess the significance of usage 142Pr in radionuclide therapy. In many studies, the dosimetric parameters of 142Pr sources were calculated by modeling 142Pr sources in the water phantom and scoring the energy deposited around it. However, the medical dosimetry calculations in water phantom consider Bremsstrahlung production, raising the question: “How important is to simulate human tissues instead of using water phantom?” This study answers these questions by estimation of 142Pr Bremsstrahlung parameters.The Bremsstrahlung parameters of 142Pr as therapeutic beta nuclides in different human tissues (adipose, blood, brain, breast, cell nucleus, eye lens, gastrointestinal tract, heart, kidney, liver, lung deflated, lymph, muscle, ovary, pancreas, cartilage, red marrow, spongiosa, yellow marrow, skin, spleen, testis, thyroid and different skeleton bones) were calculated by extending the national council for radiation protection model. The specific Bremsstrahlung constant (Γ Br), probability of energy loss by beta during Bremsstrahlung emission (P Br) and Bremsstrahlung activity (A release)Br were estimated. It should be mentioned that Monte Carlo simulation was used for estimation of 142Pr Bremsstrahlung activity based on the element compositions of different human tissues and the calculated exposures from the anthropomorphic phantoms. Γ Br for yellow marrow was smallest amount (1.1962 × 10−3 C/kg-cm2/MBq-h) compared to the other tissues and highest for cortical bone (2.4764 × 10−3 C/kg-cm2/MBq-h), and, overall, Γ Br for skeletal tissues were greater than other tissues. In addition, Γ Br breast was 1.8261 × 10−3 C/kg-cm2/MBq-h which was greater than sacrum and spongiosa bones. Moreover, according to (A release)Br of 142Pr, the patients receiving 142Pr do not have to be hospitalized for radiation precautions and the Bremsstrahlung production does not prevent the therapy for outpatients.However, modeling 142Pr source in water phantom for simulation of 142Pr source in soft tissues could be acceptable due to similarity of Γ Br in water and soft tissues; this approximation is a gross computation in the mediums encompassing high atomic numbers. These data may be practical in the investigation of Bremsstrahlung absorbed dose where 142Pr is involved in radionuclide therapy.
Keywords: Praseodymium-142; Bremsstrahlung production; Human tissues; Radionuclide therapy

Dosimetric evaluation of nanotargeted 188Re-liposome with the MIRDOSE3 and OLINDA/EXM programs by Chih-Hsien Chang; Ya-Jen Chang; Te-Wei Lee; Gann Ting; Kwo-Ping Chang (419-425).
The OLINDA/EXM computer code was created as a replacement for the widely used MIRDOSE3 code for radiation dosimetry in nuclear medicine. A dosimetric analysis with these codes was performed to evaluate nanoliposomes as carriers of radionuclides (188Re-liposomes) in colon carcinoma-bearing mice.Pharmacokinetic data for 188Re-N, N-bis (2-mercaptoethyl)-N′,N′-diethylethylenediamine (188Re-BMEDA) and 188Re-liposome were obtained for estimation of absorbed doses in normal organs. Radiation dose estimates for normal tissues were calculated using the MIRDOSE3 and OLINDA/EXM programs for a colon carcinoma solid tumor mouse model.Mean absorbed doses derived from188Re-BMEDA and 188Re-liposome in normal tissues were generally similar as calculated by MIRDOSE3 and OLINDA/EXM programs. One notable exception to this was red marrow, wherein MIRDOSE3 resulted in higher absorbed doses than OLINDA/EXM (1.53- and 1.60-fold for 188Re-BMEDA and 188Re-liposome, respectively).MIRDOSE3 and OLINDA have very similar residence times and organ doses. Bone marrow doses were estimated by designating cortical bone rather than bone marrow as a source organ. The bone marrow doses calculated by MIRDOSE3 are higher than those by OLINDA. If the bone marrow is designated as a source organ, the doses estimated by MIRDOSE3 and OLINDA programs will be very similar.
Keywords: Dosimetry; Internal radiotherapy; MIRDOSE3; OLINDA/EXM; Rhenium-188

The purpose of this study was to clarify the significance of positron emission tomography (PET) and computed tomography (CT) findings for evaluating the bone metastasis of breast cancer during therapy.Forty-seven patients with bone metastases from breast cancer who underwent sequential FDG-PET/CT studies during therapy were enrolled. A total of 771 lesions were identified. The changes in the PET and CT findings were compared with the tumor marker levels in each patient by calculating the weighted kappa value. The correlation between the PET and CT findings was examined for each lesion by an adjusted Chi-square test.The change in the tumor marker levels was substantially correlated with the PET findings and moderately correlated with the CT findings (weighted kappa = 0.780 and 0.585 for quadratic weighting, respectively). An increase in FDG uptake was correlated with lytic changes on the CT images (62/65, 95.4 %, p < 0.05). Sclerotic changes suggested improvement, but sclerosis and progression occurred at the same time in some lesions.Changes of FDG uptake are useful for evaluating individual bone metastases in cases of breast cancer during therapy. Lytic change on CT images suggests progression of bone metastasis. The lysis-progression/sclerosis-improvement pattern was observed in the majority of subjects, but a sclerosis-progression pattern was also observed. The hybrid pattern of increase of FDG uptake on PET/lytic change on CT is most accurate to show progression of bone metastases. Assessments of these processes during therapy are necessary for the precise evaluation of bone metastases.
Keywords: Breast; Bone metastasis; FDG-PET/CT; Serum tumor markers

F-18 FDG PET/CT imaging of solitary liver Langerhans cell histiocytosis: preliminary findings by Xiaoxia Hu; Aisheng Dong; Shuqing Lv; Qian Wang; Xianbao Zhan; Xianmin Song; Jianmin Wang (436-439).
Langerhans cell histiocytosis (LCH) is a disorder of clonal proliferation of Langerhans-type cells. The imaging findings of LCH are not specific. A 27-year-old woman was admitted to our hospital because of liver enzyme elevation without other hepatic signs. Radiological studies were originally interpreted as possible metastatic disease to the liver. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) images demonstrated a diffuse pattern of nodules in the liver with hypermetabolic activity. LCH was diagnosed histopathologically with an ultrasound-guided liver biopsy. This case illustrates the importance of considering proliferative/benign conditions of the liver when interpreting PET/CT. Failure to do so could result in patient mismanagement.
Keywords: Langerhans cell histiocytosis; PET-CT; Liver

Complete disappearance of uptake of FDG in the multifocal liver hemangioendothelioma after radioembolization therapy using yttrium-90 microspheres by Bulent Karaman; Bilal Battal; Engin Alagoz; Veysel Akgun; Selami Ince; Bahri Ustunsoz (440-443).
Hemangioendothelioma (HE) is an intermediate grade tumor that originates from vascular endothelium. It is rarely encountered in the liver as multifocal lesions. In the treatment of the hepatic HE, surgical resection, chemotherapy, interferon-alpha 2 therapy and liver transplantation have been described in the literature. Intra-arterial radioembolization therapy with yttrium-90 microsphere is an advanced and promising technique in the treatment of hepatic multifocal HEs. In this report, we aimed to present pre- and post-treatment radio-nuclear imaging features and to discuss radioembolization technique in a 56-year-old patient with multifocal liver HE.
Keywords: Hemangioendothelioma; Liver; PET-CT; Radioembolization; Tumor

Simultaneous PET/MR body imaging in rats: initial experiences with an integrated PET/MRI scanner by Mitsuaki Tatsumi; Seiichi Yamamoto; Masao Imaizumi; Tadashi Watabe; Yasukazu Kanai; Masaaki Aoki; Hiroki Kato; Eku Shimosegawa; Jun Hatazawa (444-449).
We recently developed an integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) (iPET/MRI) scanner for small animals, which had relatively large field-of-view (FOV) covering up to the size of a rat body. The purpose of this study was to report results of simultaneous PET/MRI of a rat body using this scanner with some radiotracers.C-11-methionine (MET), F-18-fluorodeoxyglucose (FDG), or F-18-sodium fluoride (NaF) was injected as a radiotracer for PET portion in addition to gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid, a hepatobiliary contrast agent, for MRI portion. Simultaneous PET/MRI was performed in normal rats. PET, MRI, and co-registered fusion images were evaluated regarding image quality and feasibility for rat imaging studies.MET uptake was clearly shown in the liver and pancreas, which was confirmed with magnetic resonance (MR) and fused PET/MR images. PET/MR images depicted intense FDG uptake in the brain, Harderian glands, and myocardium. NaF uptake was observed in all bones and joints within FOV, except in ribs, which was well recognized with the help of MR and fused PET/MR images.This study demonstrated that simultaneous PET/MRI with an integrated dual-modality molecular imaging scanner was a feasible technique for imaging studies targeting on a rat body. However, further developments including attenuation correction methods are required to use this technique routinely in rat imaging studies.
Keywords: PET/MRI; Rat; 11C-methionine; 18F-FDG; 18F-NaF