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Annals of Nuclear Medicine (v.26, #4)

Outpatient therapeutic nuclear oncology by J. Harvey Turner (pp. 289-297).

In the beginning, nuclear medicine was radionuclide therapy, which has evolved into molecular tumour-targeted control of metastatic cancer. Safe, efficacious, clinical practice of therapeutic nuclear oncology may now be based upon accurate personalised dosimetry by quantitative gamma SPECT/CT imaging to prescribe tumoricidal activities without critical organ toxicity. Preferred therapy radionuclides possess gamma emission of modest energy and abundance to enable quantitative SPECT/CT imaging for calculation of the beta therapy dosimetry, without radiation exposure risk to hospital personnel, carers, family or members of the public. The safety of outpatient radiopharmaceutical therapy of cancer with Iodine-131, Samarium-153, Holmium-166, Rhenium-186, Rhenium-188, Lutetium-177 and Indium-111 is reviewed. Measured activity release rates and radiation exposure to carers and the public are all within recommendations and guidelines of international regulatory agencies and, when permitted by local regulatory authorities allow cost-effective, safe, outpatient radionuclide therapy of cancer without isolation in hospital.

Keywords: Radiation protection; Radionuclide cancer treatment; Personalised dosimetry

Pulmonary function–morphologic relationships assessed by SPECT–CT fusion images by Kazuyoshi Suga (pp. 298-310).

Pulmonary single photon emission computed tomography-computed tomography (SPECT–CT) fusion images provide objective and comprehensive assessment of pulmonary function and morphology relationships at cross-sectional lungs. This article reviewed the noteworthy findings of lung pathophysiology in wide-spectral lung disorders, which have been revealed on SPECT–CT fusion images in 8 years of experience. The fusion images confirmed the fundamental pathophysiologic appearance of lung low CT attenuation caused by airway obstruction-induced hypoxic vasoconstriction and that caused by direct pulmonary arterial obstruction as in acute pulmonary thromboembolism (PTE). The fusion images showed better correlation of lung perfusion distribution with lung CT attenuation changes at lung mosaic CT attenuation (MCA) compared with regional ventilation in the wide-spectral lung disorders, indicating that lung heterogeneous perfusion distribution may be a dominant mechanism of MCA on CT. SPECT–CT angiography fusion images revealed occasional dissociation between lung perfusion defects and intravascular clots in acute PTE, indicating the importance of assessment of actual effect of intravascular colts on peripheral lung perfusion. Perfusion SPECT–CT fusion images revealed the characteristic and preferential location of pulmonary infarction in acute PTE. The fusion images showed occasional unexpected perfusion defects in normal lung areas on CT in chronic obstructive pulmonary diseases and interstitial lung diseases, indicating the ability of perfusion SPECT superior to CT for detection of mild lesions in these disorders. The fusion images showed frequent “steal phenomenon”-induced perfusion defects extending to the surrounding normal lung of arteriovenous fistulas and those at normal lungs on CT in hepatopulmonary syndrome. Comprehensive assessment of lung function–CT morphology on fusion images will lead to more profound understanding of lung pathophysiology in wide-spectral lung disorders.

Keywords: Single photon emission computed tomography (SPECT); Pulmonary perfusion; Pulmonary ventilation; SPECT–CT fusion images

Prognostic implications of microscopic involvement of surgical resection margin in patients with differentiated papillary thyroid cancer after high-dose radioactive iodine ablation by Chae Moon Hong; Byeong-Cheol Ahn; Ji Young Park; Shin Young Jeong; Sang-Woo Lee; Jaetae Lee (pp. 311-318).

To evaluate the relationship between microscopic cancerous involvement of surgical margin and recurrence in patients with differentiated papillary thyroid cancer (PTC) who underwent total thyroidectomy followed by high-dose radioactive iodine ablation (HDRIA).Consecutive 197 PTC patients (184 women; mean age 44.9 years) who underwent total thyroidectomy without gross residual tumor followed by HDRIA were retrospectively reviewed. Resection margin involvement was evaluated and recurrence of the disease was assessed with clinicopathologically. Recurrence detected within 12 months after HDRIA were defined as early recurrence, detected after 12 months were defined as late recurrence.The mean follow-up was 85.9 ± 16.6 months. Twelve patients (6.1%) had microscopic cancerous involvement of surgical margin [margin (+) group], and 185 patients had negative surgical resection margins [margin (−) group]. Three patients (25.0%) in the margin (+) group and 11 patients (5.9%) in the margin (−) group had early recurrence. Margin (+) group showed higher incidence of early recurrence and lower incidence of disease free compared to margin (−) group (25.0 vs. 5.9%, p < 0.01; 66.7 vs. 81.1%, p < 0.01, respectively); however, there was no difference in incidence of late recurrence between the two groups (p = 1.00). There were no significant differences in the disease-free survival between the margin (+) and margin (−) groups after exclusion of early recurrence (p = 0.78).After high-dose radioactive iodine ablation, PTC patients with microscopic cancerous surgical margin involvement had a higher incidence of early recurrence and no different late recurrence rate compared to patients without microscopic cancerous surgical margin involvement.

Keywords: Papillary thyroid cancer; Resection margin involvement; Prognosis; Early recurrence; Radioactive iodine ablation

Usefulness of extent analysis for statistical parametric mapping with asymmetry index using inter-ictal FGD-PET in mesial temporal lobe epilepsy by Tsutomu Soma; Toshimitsu Momose; Miwako Takahashi; Keitraro Koyama; Kensuke Kawai; Kenya Murase; Kuni Ohtomo (pp. 319-326).

Inter-ictal ¹⁸F-2-fluoro-deoxy-d-glucose-positron emission tomography (FDG-PET) is widely used for preoperative evaluation to identify epileptogenic zones in patients with temporal lobe epilepsy. In this study, we combined statistical parametric mapping (SPM) with the asymmetry index and volume-of-interest (VOI) based extent analysis employing preoperative FDG-PET in unilateral mesial temporal lobe epilepsy (MTLE) patients. We also evaluated the detection utility of these techniques for automated identification of abnormalities in the unilateral hippocampal area later confirmed to be epileptogenic zones by surgical treatment and subsequent good seizure control.FDG-PET scans of 17 patients (9 males, mean age 35 years, age range 16–60 years) were retrospectively analyzed. All patients had been preoperatively diagnosed with unilateral MTLE. The surgical outcomes of all patients were Engel class 1A or 1B with postoperative follow-up of 2 years. FDG-PET images were spatially normalized and smoothed. After two voxel-value adjustments, one employing the asymmetry index and the other global normalization, had been applied to the images separately, voxel-based statistical comparisons were performed with 20 controls. Peak analysis and extent analysis in the VOI in the parahippocampal gyrus were conducted for SPM. For the extent analysis, a receiver operating characteristic (ROC) curve was devised to calculate the area under the curve and to determine the optimal threshold of extent.The accuracy of the method employing the asymmetry index was better than that of the global normalization method for both the peak and the extent analysis. The ROC analysis results, for the extent analysis, yielded an area under the curve of 0.971, such that the accuracy and optimal extent threshold of judgment were 92 and 32.9%, respectively.Statistical z-score mapping with the asymmetry index was more sensitive for detecting regional glucose hypometabolism and more accurate for identifying the side harboring the epileptogenic zone using inter-ictal FDG-PET in unilateral MTLE than z-score mapping with global normalization. Moreover, the automated determination of the side with the epileptogenic zone in unilateral MTLE showed improved accuracy when the combination of SPM with the asymmetry index and extent analysis was applied based on the VOI in the parahippocampal gyrus.

Keywords: Asymmetry index; Statistical parametric mapping; FDG-PET; Mesial temporal lobe epilepsy

Indeterminate pleural metastasis on contrast-enhanced chest CT in non-small cell lung cancer: improved differential diagnosis with ¹⁸F-FDG PET/CT by Min-Young Jung; Ari Chong; Hyun Ju Seon; Song Choi; Yun-Hyeon Kim; Sang Soo Shin; Jin Woong Kim; Hee-Seung Bom (pp. 327-336).

To evaluate the diagnostic performance of ¹⁸F-fluorodeoxyglucose (FDG) PET/CT (PET/CT) for determining the presence of pleural metastasis in patients with indeterminate findings on a contrast-enhanced chest CT (CECT) for non-small cell lung cancer (NSCLC).This is a retrospective study. NSCLC patients (n = 63) who underwent thoracentesis and/or pleural biopsy were enrolled. CECT and PET/CT reports of pleural metastasis were analyzed based on comparison with cytological or histological confirmation. Negative cytologic results were re-confirmed with follow-up study prior to cancer-related therapy. CECT results were classified into 3 categories: negative, indeterminate, and positive for pleural metastasis. PET/CT results were classified into 2 categories (negative and positive for pleural metastasis) based on FDG uptake visual grading. The level of max SUV of pleura was also analyzed. ROC analysis was done for establishing the max SUV cut-off value.PET/CT could differentiate pleural metastasis with 70.8% diagnostic accuracy when the CECT finding was indeterminate (n = 24). Optimal cut-off value to predict pleural metastasis was 2.8 for max SUV. Diagnosis by max SUV 2.8 had lower sensitivity (86.3 vs. 92.2%), but higher specificity (66.7 vs. 58.3%) than PET/CT by FDG visual grading criteria.PET/CT showed better diagnostic performance than CECT for detecting pleural metastasis in NSCLC patients. When the finding of CECT is controversial, PET/CT can differentiate the metastatic pleural lesion. Both FDG uptake visual grading and max SUG cut-off value can be used as diagnostic criteria for pleural metastasis.

Keywords: NSCLC; Pleural metastasis; Chest CT; ¹⁸F FDG; Integrated PET/CT

SPECT study with I-123-Ioflupane (DaTSCAN) in patients with essential tremor. Is there any correlation with Parkinson’s disease? by G. Gerasimou; D. C. Costa; E. Papanastasiou; S. Bostanjiopoulou; M. Arnaoutoglou; E. Moralidis; T. Aggelopoulou; A. Gotzamani-Psarrakou (pp. 337-344).

The differential diagnosis between essential tremor (ET) and Parkinson’s disease (PD) may be, in some cases, very difficult on clinical grounds alone. In addition, it is accepted that a small percentage of ET patients presenting symptoms and signs of possible PD may progress finally to a typical pattern of parkinsonism. Ioflupane, N-u-fluoropropyl-2a-carbomethoxy-3a-(4-iodophenyl) nortropane, also called FP-CIT, labelled with ¹²³I (commercially known as DaTSCAN) has been proven to be useful in the differential diagnosis between PD and ET and to confirm dopaminergic degeneration in patients with parkinsonism. The aim of this study is to identify dopaminergic degeneration in patients with PD and distinguish them from others with ET using semi-quantitative SPECT ¹²³I-Ioflupane (DaTSCAN) data in comparison with normal volunteers (NV), in addition with the respective ones of patients referred as suffering from ET, as well as, of patients with a PD diagnosis at an initial stage with a unilateral presentation of motor signs.Twenty-eight patients suffering from ET (10 males plus 18 females) and 28 NV (12 males and 16 females) were enroled in this study. In addition, 33 patients (11 males and 22 females) with an established diagnosis of PD with unilateral limb involvement (12 left hemi-body and 21 right hemi-body) were included for comparison with ET. We used DaTSCAN to obtain SPECT images and measure the radiopharmaceutical uptake in the striatum (S), as well as the caudate nucleus (CN) and putamen (P) in all individuals.Qualitative (Visual) interpretation of the SPECT data did not find any difference in the uptake of the radiopharmaceutical at the level of the S, CN and P between NV and ET patients. Reduced accumulation of the radiopharmaceutical uptake was found in the P of all PD patients. Semiquantitative analysis revealed significant differences between NV and ET patients in the striatum, reduced in the latter. There was also a significant reduction in the tracer accumulation in the left putamen of patients with right hemi-parkinsonism compared to ET and NV. Patients with left hemi-parkinsonism, demonstrated reduced radioligand uptake in the right putamen in comparison with ET and NV. Clinical follow-up of 20 patients with ET at (so many months afterwards) revealed no significant change in clinical presentation, particularly no signs of PD. Follow-up DaTSCAN performed in 10 of them (so many months afterwards) was negative in all but one. This one had an equivocal baseline study which deteriorated 12 months later.Our results do not support the hypothesis of a link between essential tremor and Parkinson’s disease. However, it appears that ET patients have a small degree of striatal dopaminergic degeneration. If this is due to alterations in the nigrostriatl pathway or of other origin it is not clear. Follow-up studies of essential tremor patients are warranted to assess progression of disease and to understand better the possible cause for striatal dopaminergic degeneration.

Keywords: Essential tremor; Parkinson’s disease; DaTSCAN

Increased FDG uptake in breast cancer is associated with prognostic factors by Yasemin Sanli; Serkan Kuyumcu; Zeynep Gozde Ozkan; Göknur Işık; Hasan Karanlik; Burcu Guzelbey; Cuneyt Turkmen; Sevda Ozel; Ekrem Yavuz; Ayse Mudun (pp. 345-350).

To evaluate the relationship between FDG uptake and prognostic factors of breast cancer such as hormone receptors (estrogen and progesterone), expression of c-erbB-2, axillary lymph node status, tumor histology, grade and size.Between May 2009 and February 2011; 79 patients (mean age ± SD: 52.9 ± 13.9 years) with biopsy proven breast cancer underwent F-18 FDG PET/CT scanning for staging. Patients with excisional biopsy or neoadjuvant chemotherapy were excluded from the study. Histological types included were invasive ductal carcinoma (n = 68), invasive lobular carcinoma (n = 2), and invasive ductal plus lobular mixed carcinoma (n = 9). Maximum standardized uptake values (SUVmax) were compared with estrogen (ER) and progesterone receptors (PR), expression of c-erbB-2, as well as tumor grade and tumor size. For the evaluation of relationship between tumor SUVmax values and prognosticators such as hormone receptors, tumor histologic grade, and tumor size, statistical analyses were performed using Student t test, Mann–Whitney U Test and Pearson correlation coefficient and p values of less than 0.05 were considered to indicate statistically significant differences.All primary breast neoplasms were detected by PET/CT scanner. The mean SUVmax values and breast cancer tumor sizes ranged from 2.09 to 39.0 and 0.7 to 10 cm, respectively. Tumors with negative ER [(n = 19); SUVmax median (min–max): 15 (2.09–39.0)] were associated with higher SUVmax values (p = 0.01). Tumors with overexpression of C-erbB-2 [(n = 28); SUVmax median (min–max): 16.0 (5.0-39.0)]; tumor grade 3 [(n = 25); SUVmax median (min–max): 15 (6.43–39)]; axillary lymph node involvement [(n = 60); SUVmax median (min–max): 13.61 (4.0–39.0)]; tumor histopathology and increased tumor size were associated with higher maximum standardized uptake values. However, PR did not show any relationship with SUVmax values.In the present report, strong relationships were detected between the negativity of ER, overexpression of c-erbB-2, tumor grade, tumor size, histopathology, axillary lymph node involvement and SUVmax values. Accordingly, we believe that SUVmax values obtained with ¹⁸F-FDG PET/CT may provide some information about tumor biology of breast cancer.

Keywords: Breast cancer; FDG PET/CT; Hormone receptors; c-erbB-2

Improvement of the ^99mTc-ECD brain uptake ratio (BUR) method for measurement of cerebral blood flow by Shigeki Ito; Akihiro Takaki; Shinya Inoue; Seiji Tomiguchi; Shinya Shiraishi; Yasuhiko Akiyama; Toshiaki Sasaki; Satoshi Odajima; Satomi Teraoka; Tetsuo Hosoya; Tsutomu Soma; Yoshiharu Miyazaki; Seigo Kinuya; Yasuyuki Yamashita (pp. 351-358).

The brain uptake ratio (BUR) method for the ^99mTc-ECD SPECT, a non-invasive measurement method of rCBF, has been used in clinical practice in Japan, because it is simple to use. However, the accuracy of this method is limited, as it has problems in the determination of input function and the regression equation. The purpose of this study is to improve the BUR method by reconstructing the determination process of the input function and regression equation based on measurement of the rCBF by H ₂ ¹⁵ O PET.The input function was obtained by setting the region of interest on the ascending aorta instead of the aortic arch. The 3DSRT algorithm was used to obtain the anatomically standardized rCBF, and developed a semi-automatic analyzing software using C++ in order to stabilize the repeatability of the improved BUR (IBUR) method. The regression equation for the IBUR method was obtained by the H ₂ ¹⁵ O PET rCBFs in 15 patients with the arterial blood sampling method. All the measurements in this study were performed with the patient in the resting state.A good correlation was observed between the rCBF values measured by H ₂ ¹⁵ O PET and the regional BURs measured by the IBUR method (r = 0.86, p < 0.0001). The rCBF values were calculated for only 5 min using a semi-automatic analyzing software.The BUR method was improved by changing the location of the input function from the aortic arch to the ascending aorta based on arterial blood flow dynamics, and reconstructing regression equation based on the rCBF values obtained using H ₂ ¹⁵ O PET. This finding indicates the potential clinical usefulness of this method.

Keywords: rCBF; Brain uptake ratio; ^99mTc-ECD SPECT; Input function; Non-invasive measurement method

CT tube current for attenuation map in a combined PET/CT system: obese patient simulated phantom study by Akio Nagaki; Masahisa Onoguchi; Norikazu Matsutomo (pp. 359-364).

The CT portion of PET/CT provides attenuation correction of the PET emission scan. This study was performed to evaluate how much the CT tube current can be lowered while still providing attenuation maps on PET images.Two body phantoms (outside diameters of 300 and 500 mm) were used to investigate, and PET/CT acquisitions were performed with an Aquiduo PCA-7000B (Toshiba Medical Systems, Otawara, Japan). The CT scan was performed with the following parameters (120 kVp; 0.5-s rotation; 10, 20, 40, 80, 160, 200, 320, 460 mA). After the CT scan, PET images for ¹⁸F-FDG (5.3 kBq/mL) were obtained for 4 min/bed position. The linear attenuation coefficients for ¹⁸F-FDG in 300- and 500-mm phantoms, pixel values and SD of CT images, radioactivity concentration values and hot- and cold-sphere contrast on PET images in the 500-mm phantom were evaluated.In the 300-mm phantom, all eight tube currents gave average linear attenuation coefficients of approximately 0.095 cm⁻¹. In contrast, the average linear attenuation coefficients of the 500-mm phantom at 10, 20, and 40 mA were significantly decreased (0.081, 0.087, and 0.092 cm⁻¹, respectively; p < 0.05) as compared to 0.096 cm⁻¹ of the other tube currents. Further, CT pixel values decreased 10 and 20 mA. Thus, the background radioactivity concentration values at 10 and 20 mA were substantially underestimated to be 57 and 80%, respectively (p < 0.05); the hot-sphere contrast values at 10 and 20 mA were 0.26 and 0.29; the cold-sphere contrast values at 10, 20, and 40 mA were −0.33, −0.16, and 0.08.Although the linear attenuation coefficients in the 300-mm phantom remained the same with varying CT tube currents, the 500-mm phantom yielded significant differences in the range 10–40 mA. Therefore, the CT tube currents for attenuation correction should be adjusted over 40 mA in obese patients.

Keywords: ¹⁸F-FDG PET; CT tube current; Attenuation map; PET/CT; Obese patient

Peptide receptor radionuclide therapy of Merkel cell carcinoma using ¹⁷⁷lutetium-labeled somatostatin analogs in combination with radiosensitizing chemotherapy: a potential novel treatment based on molecular pathology by Ali Salavati; Vikas Prasad; Claus-Peter Schneider; Rudolf Herbst; Richard Paul Baum (pp. 365-369).

Few studies have been published on the safety and feasibility of synchronous use of peptide receptor radionuclide therapy (PRRNT), as source of internal radiation therapy, in combination with chemotherapy. In this study we reported a 53-year-old man with stage IV Merkel cell carcinoma (MCC), who underwent synchronous internal radiation therapy and chemotherapy. Based on presumable poor prognosis with chemotherapy only, functional similarities of MCC with other neuroendocrine tumors and available evidence of effectiveness and safety of synchronous use of external beam radiation therapy and chemotherapy in treatment of high-risk MCC patients, our interdisciplinary neuroendocrine tumor board recommended him to add PRRNT to his ongoing chemotherapy. He received 2 courses of ¹⁷⁷Lu-DOTATATE(1, 4, 7, 10-Tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-1-D-Phe1-Tyr3-Thr8-octreotide) in combination with ongoing 8 cycles of liposomal doxorubicin based on standard protocols. Response to therapy was evaluated by ¹⁸F-FDG and ⁶⁸gallium-somatostatin-receptor PET/CT. There was an impressive improvement of the clinical symptoms. However, follow-up PET/CT studies showed mixed pattern of response. Synchronous use of PRRNT and radiosensitizing chemotherapy seems safe and feasible in high risk MCC patients, however, further prospective studies and clinical trials are warranted to provide reliable evidence of possible pitfalls and effectiveness of PRRNT and ⁶⁸Ga-somatostatin-receptor PET/CT in the management of MCC.

Keywords: Merkel cell carcinoma; Peptide receptor radionuclide therapy; ⁶⁸Ga-somatostatin-receptor PET/CT; Synchronous chemo-radiation therapy

Thyroid remnant ablation using 1,110 MBq of I-131 after total thyroidectomy: regulatory considerations on release of patients after unsealed radioiodine therapy by Kiyoko Kusakabe; Kunihiko Yokoyama; Koichi Ito; Hiroshi Shibuya; Seigo Kinuya; Mitsuru Ito; Tatsuya Higashi; Takashi Togawa; Kiyoshi Koizumi; Mana Yoshimura; Mayuki Uchiyama; Takahiro Okamoto; Shinichi Kanaya; Kazuko Kanaya; Tatsuya Yoneyama; Hideharu Ikebuchi; Sachiko Yanagida; Keigo Shibata; Koji Segawa; Atsushi Yamamoto (pp. 370-378).

This study was undertaken to measure the radiation exposure level of caregivers following outpatient NaI (I-131) 1,110 MBq therapy for remnant thyroid ablation after total thyroidectomy in patients with differentiated thyroid cancer, and to evaluate the influence of activities of daily living on radiation exposure level, with the goal of proposing an optimum method of I-131 therapy.The study included 37 patients with differentiated thyroid cancer, who had undergone total thyroidectomy and received outpatient based remnant thyroid ablation using NaI (I-131) 1,110 MBq, who were satisfying the following requirements: (1) patients who have no evidence of distant metastases, (2) whose living environments were appropriate for outpatient I-131 (1,110 MBq) therapy, and (3) patients who gave written informed consent.The dose rate at a distance of 1 m from the body surface of the patient at the moment of release was measured using survey meters of the GM type or ionization chamber type. The dose level for the caregiver was measured with a personal dosimeter in all cases.The dose rate at a distance of 1 m from the patient’s body surface 1 h after I-131 administration was in the range of 29–115 μSv/h (mean 63.8 μSv/h). The 7-day cumulative effective dose of caregivers was 0.11 ± 0.08 mSv, on an average, in 34 dosimeters. In 31 of 34 dosimeters, cumulative effective dose of caregivers was below 0.2 mSv. Dose levels exceeding 0.2 mSv were recorded in 3 cases (0.21, 0.35 and 0.43 mSv in one case each). These results suggest that the exposure level of family members (caregiver and others) was minimal and is lower than the radiation levels affecting human environments.Outpatient-based remnant thyroid ablation with I-131 (1,110 MBq) performed after total thyroidectomy in patients with differentiated thyroid cancer is safe if applied in accordance with the appropriate supervision and guidance by experts with certain qualifications.

Keywords: Thyroid; Remnant ablation; Outpatient

Erratum to: PET scanning in plastic and reconstructive surgery by Eirini Liodaki; Emmanouil Liodakis; Othonas Papadopoulos; Hans-Günther Machens; Nikolaos A. Papadopulos (pp. 379-379).

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Annals of Nuclear Medicine (v.26, #4)