Nuclear medicine practice in Japan: a report of the ninth nationwide survey in 2022.

Subcommittee on Survey of Nuclear Medicine Practice in Japan has performed a nationwide survey of nuclear medicine practice every 5 years since 1982 to survey contemporary nuclear medicine practice and its changes over the years. The subcommittee sent questionnaires, including the number and category of examinations as well as the kind of the radiopharmaceuticals during the 30 days of June 2022 to all nuclear medicine institutes in Japan. The total numbers of them for the year 2022 were estimated depends on the 1-month data. A total of 1095 institutes responded to the survey, including 364 positron emission tomography (PET) centers. The recovery rate was 90.6%. The number of gamma cameras installed was 1299 in total, with 2.5% decrease in 5 years. Dual-head cameras and hybrid SPECT/CT scanners accounted for 83.8% and 35.5%, respectively. The number of single-photon tracer studies in 2022 was 1.11 million which means increase in 2.7% in 5 years. Bone scintigraphy was a leading examination (31.0%), followed by myocardial scintigraphy (27.1%) and cerebral perfusion study (23.8%) in order. The percentage of SPECT studies showed an increase from 63.5% in previous survey to 66.8% in this survey. PET centers have also increased from 389 to 412, as compared with the previous one. One hundred and twenty-two PET centers have installed one or two in-house cyclotrons. Increasing trends of the PET studies were observed from 1992 to 2017, the trend changed and PET studies showed 1.5% decrease in 5 years. 18F-FDG accounted for 98.6% (610,497 examinations). PET examinations using 11C-methionine, 13N-NH3 and 11C-PIB have decreased, with 1624, 2146 and 525 examinations, respectively in 2022. The total number of nuclear medicine examination was eventually increased by 1.0%. Therapies for pheochromocytoma or paraganglioma (PPGL) with 131I-MIBG and for neuroendocrine tumor with 177Lu-DOTA-TATE were newly started, however, a total number of targeted radionuclide therapy was decreased by 17.7% because 131I-radioiodine and 223Ra targeted therapies were decreased and supply of some radioisotopes was discontinued. 131I-radioiodine targeted therapy showed a decrease in 5 years (- 15.9%), including 4099 patients for thyroid cancer. The number of out-patient thyroid bed ablation therapy with 1110 MBq of 131I was also decreased to 1015 per year. The number of admission rooms specialized for radionuclide targeted therapy increased from 157 to 160. The number of 223Ra targeted therapies for castration-resistant metastatic prostate cancer (mCRPC) was 1041 patients. This survey was performed during COVID-19 pandemic, however, total number of nuclear medicine examinations was almost same as previous survey (+ 1.0%). Radionuclide therapies with 131I-MIBG and 177Lu-DOTA-TATE were newly started, and new radionuclide therapy will be available in future, therefore, the development of radionuclide therapy will be continued. We are convinced that this survey report is useful in understanding the current status of the nuclear medicine practice in Japan, and in devising the new strategy to strengthen a role of nuclear medicine.

A Case of Rectal Dissemination of Gastric Cancer Diagnosed by Simultaneous 18 F-FDG PET/MRI.

ABSTRACT: Metastatic rectal cancer is rare and difficult to differentiate from primary rectal cancer. A 79-year-old man with a rectal mass detected by CT during postoperative follow-up of gastric cancer underwent 18 F-FDG PET/MRI. Fused PET/MRI images revealed a lower FDG uptake within the mass, which appeared to surround the outside of the rectum, than in the rectal wall, suggesting rectal dissemination of gastric cancer. PET/MRI was useful for differentiating between mass and rectal wall uptake, because of the high contrast resolution of MRI and precise image fusion made possible by simultaneous image acquisition.

[18F]FES PET Resolves the Diagnostic Dilemma of COVID-19-Vaccine-Associated Hypermetabolic Lymphadenopathy in ER-Positive Breast Cancer.

Coronavirus disease (COVID-19) vaccination is known to cause a diagnostic dilemma due to false-positive findings on [18F]FDG PET in vaccine-associated hypermetabolic lymphadenopathy. We present two case reports of women with estrogen-receptor (ER)-positive cancer of the breast who were vaccinated for COVID-19 in the deltoid muscle. [18F]FDG positron emission tomography (PET) demonstrated primary breast cancer and multiple axillary lymph nodes with increased [18F]FDG uptake, diagnosed as vaccine-associated [18F]FDG-avid lymph nodes. Subsequent [18F]FES PET revealed single axillary lymph node metastasis in the vaccine-associated [18F]FDG-avid lymph nodes. To the best of our knowledge, this is the first study showing the usefulness of [18F]FES PET in diagnosing axillary lymph node metastasis in COVID-19-vaccinated patients harboring ER-positive breast cancer. Thus, [18F]FES PET has potential applications in the detection of true-positive metastatic lymph nodes in patients with ER-positive breast cancer regardless of the ipsilateral or contralateral side, who have received COVID-19 vaccination.

Rapid Whole-Body FDG PET/MRI in Oncology Patients: Utility of Combining Bayesian Penalised Likelihood PET Reconstruction and Abbreviated MRI.

This study evaluated the diagnostic value of a rapid whole-body fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) approach, combining Bayesian penalised likelihood (BPL) PET with an optimised ß value and abbreviated MRI (abb-MRI). The study compares the diagnostic performance of this approach with the standard PET/MRI that utilises ordered subsets expectation maximisation (OSEM) PET and standard MRI (std-MRI). The optimal ß value was determined by evaluating the noise-equivalent count (NEC) phantom, background variability, contrast recovery, recovery coefficient, and visual scores (VS) for OSEM and BPL with ß100-1000 at 2.5-, 1.5-, and 1.0-min scans, respectively. Clinical evaluations were conducted for NECpatient, NECdensity, liver signal-to-noise ratio (SNR), lesion maximum standardised uptake value, lesion signal-to-background ratio, lesion SNR, and VS in 49 patients. The diagnostic performance of BPL/abb-MRI was retrospectively assessed for lesion detection and differentiation in 156 patients using VS. The optimal ß values were ß600 for a 1.5-min scan and ß700 for a 1.0-min scan. BPL/abb-MRI at these ß values was equivalent to OSEM/std-MRI for a 2.5-min scan. By combining BPL with optimal ß and abb-MRI, rapid whole-body PET/MRI could be achieved in ≤1.5 min per bed position, while maintaining comparable diagnostic performance to standard PET/MRI.

FDG PET/MRI in Synchronous Uterine Adenocarcinoma and Leiomyosarcoma.

ABSTRACT: A 52-year-old woman with a rapidly growing uterine tumor suspected of uterine sarcoma underwent 18F-FDG PET/MRI, revealing a myometrial mass and an endometrial lesion, suggesting dual primary neoplasms. Based on the PET/MRI findings, we changed the intraoperative procedure to determine the necessity of pelvic lymphadenectomy. PET/MRI was useful in diagnosing and differentiating between 2 malignant neoplasms in the uterus compared with PET/CT, due to MRI's high contrast resolution and precise fusion due to the simultaneous acquisition.

PET/MRI is useful for early detection of pelvic insufficiency fractures after radiotherapy for cervical cancer.

Radiotherapy (RT) is used to manage cervical cancer, and pelvic insufficiency fracture (PIF) is known as a late complication of RT. The present study identified risk factors for PIF after radiotherapy for cervical cancer, and investigated its incidence rate. It also considered the usefulness of positron emission tomography/magnetic resonance imaging (PET/MRI) in PIF diagnosis. A total of 149 patients with cervical cancer who received definitive or adjuvant RT with/without concurrent chemotherapy between January 2013 and December 2018 were investigated in the present study and followed up for more than one month after RT at Kobe University Hospital. The median follow-up period was 32 months (range, 1-87 months), and the median age of all patients was 66 years (age range, 34-90 years). Computed tomography (CT), MRI, PET/CT or PET/MRI were used for image examination. Among the 149 patients, 31 (20.8%) developed PIF. The median age of these patients was 69 years (age range, 44-87 years). Univariate analysis using the log-rank test demonstrated that age (≥60 years) was significantly associated with PIF. The median maximum standardized uptake value of PIF sites on PET/CT was 4.32 (range, 3.04-4.81), and that on PET/MRI was 3.97 (range, 1.21-5.96) (P=0.162). Notably, the detection time of PIF by PET/MRI was significantly earlier compared with PET/CT (P<0.05). The incidence of PIF after RT for cervical cancer was 20.8%, and age was significantly associated with risk factors for such fractures. Taken together, these results suggest that PET/MRI, which offers the advantage of decreased radiation exposure to the patient, is useful for diagnosing PIF and can detect it earlier than PET/CT imaging.

Quantitative bone single-photon emission computed tomography imaging for uninfected nonunion: comparison of hypertrophic nonunion and non-hypertrophic nonunion.

BACKGROUND: Recently, a standardized uptake value (SUV) has been used to evaluate bone single-photon emission computed tomography (SPECT). The aim of this study was to investigate quantitative SPECT imaging of uninfected nonunion to compare hypertrophic nonunion and non-hypertrophic nonunion using volume-based parameters. METHODS: We evaluated 23 patients with uninfected nonunion who underwent SPECT acquisition 3 h after an injection of 99mTc-hydroxymethylene diphosphonate or 99mTc-methylene diphosphonate from April 2014 to November 2019. We reconstructed the acquired data and performed voxel-based quantitative analysis using the GI-BONE software. Quantitative parameters, maximum SUV (SUVmax), peak SUV (SUVpeak), and mean SUV (SUVmean) in the high and low uptake areas of nonunion were compared between hypertrophic nonunion and non-hypertrophic nonunion. The contralateral limb was used as a control, and the ratios of the quantitative parameters were calculated. RESULTS: The values for the quantitative parameters (high uptake area/low uptake area, respectively), SUVmax control ratio (12.13 ± 4.95/6.44 ± 4.71), SUVpeak control ratio (11.65 ± 4.58/6.45 ± 4.64), and SUVmean control ratio (11.94 ± 5.03/6.28 ± 4.95) for hypertrophic nonunion were higher than those for non-hypertrophic nonunion (7.82 ± 4.76/3.41 ± 2.09 (p = 0.065/0.12), 7.56 ± 4.51/3.61 ± 2.23 (p = 0.065/0.22), and 7.59 ± 5.18/3.05 ± 1.91 (p = 0.076/0.23)). CONCLUSIONS: SUVmax, SUVpeak, and SUVmean control ratios obtained from bone SPECT images can quantitatively evaluate the biological activity of nonunions and may be an effective evaluation method for treatment decisions, especially the necessity of autologous bone grafting.

In vivo evaluation of percutaneous carbon dioxide treatment for improving intratumoral hypoxia using 18F-fluoromisonidazole PET-CT.

Carbon dioxide (CO2) treatment is reported to have an antitumor effect owing to the improvement in intratumoral hypoxia. Previous studies were based on histological analysis alone. In the present study, the improvement in intratumoral hypoxia by percutaneous CO2 treatment in vivo was determined using 18F-fluoromisonidazole positron emission tomography-computed tomography (18F-FMISO PET-CT) images. Twelve Japanese nude mice underwent implantation of LM8 tumor cells in the dorsal subcutaneous area 2 weeks before percutaneous CO2 treatment and 18F-FMISO PET-CT scans. Immediately after intravenous injection of 18F-FMISO, CO2 and room air were administered transcutaneously in the CO2-treated group (n=6) and a control group (n=6), respectively; each treatment was performed for 10 minutes. PET-CT was performed 2 h after administration of 18F-FMISO. 18F-FMISO tumor uptake was quantitatively evaluated using the maximum standardized uptake value (SUVmax), tumor-to-liver ratio (TLR), tumor-to-muscle ratio (TMR), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Mean ± standard error of the mean (SEM) of the tumor volume was not significantly different between the two groups (CO2-treated group, 1.178±0.450 cm3; control group, 1.368±0.295 cm3; P=0.485). Mean ± SEM of SUVmax, TLR, MTV (cm3) and TLG were significantly lower in the CO2-treated group compared with the control group (0.880±0.095 vs. 1.253±0.071, P=0.015; 1.063±0.147361 vs. 1.455±0.078, P=0.041; 0.353±0.139 vs. 1.569±0.438, P=0.015; 0.182±0.070 vs. 1.028±0.338, P=0.015), respectively. TMR was not significantly different between the two groups (4.520±0.503 vs. 5.504±0.310; P=0.240). In conclusion, 18F-FMISO PET revealed that percutaneous CO2 treatment improved intratumoral hypoxia in vivo. This technique enables assessment of the therapeutic effect in CO2 treatment by imaging, and may contribute to its clinical application.

Prediction of post-hepatectomy liver failure using gadoxetic acid-enhanced magnetic resonance imaging for hepatocellular carcinoma with portal vein invasion.

PURPOSE: Accurate prediction of post-hepatectomy liver failure (PHLF) is important in advanced hepatocellular carcinoma (HCC). We aimed to retrospectively evaluate the utility of gadoxetic acid-enhanced MRI for predicting PHLF in patients who underwent anatomic hepatectomy for HCC with portal vein invasion. METHODS: Forty-one patients (32 men, 9 women) were included. Hepatobiliary-phase MR images were acquired 20 min after injection of gadoxetic acid using a 3D fat-suppressed T1-weighted spoiled gradient-echo sequence. Liver-spleen ratio (LSR), remnant hepatocellular uptake index (rHUI), and HUI were calculated. The severity of PHLF was defined according to the International Study Group of Liver Surgery. Differences in LSR between the resected liver and the remnant liver, and HUI and rHUI/HUI between no/mild and severe PHLF were compared using the Wilcoxon signed-rank test and Wilcoxon rank-sum test, respectively. Univariate and multivariate logistic regression analyses were performed to identify predictors of severe PHLF. Areas under the receiver operating characteristic curves (AUCs) of rHUI and rHUI/HUI were calculated for predicting severe PHLF. RESULTS: Nine patients developed severe PHLF. LSR of the remnant liver was significantly higher than that of the resected liver (P < 0.001). Severe PHLF demonstrated significantly lower rHUI (P < 0.001) and rHUI/HUI (P < 0.001) compared with no/mild PHLF. Multivariate logistic regression analysis showed that decreased rHUI (P = 0.012, AUC=0.885) and rHUI/HUI (P = 0.002, AUC=0.852) were independent predictors of severe PHLF. CONCLUSION: Gadoxetic acid-enhanced MRI can be a promising noninvasive examination for assessing global and regional liver function, allowing estimation of the functional liver remnant and accurate prediction of severe PHLF before hepatic resection.

Magnetic resonance imaging of intraocular optic nerve disorders: review article.

The optic nerve is morphologically classified as a peripheral nerve, but histologically it shares characteristics with the central nerves. Diseases that affect vision and the optic nerve are many and varied: optic neuritis, demyelination (multiple sclerosis, acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-related disorders), drugs, collagen disease, vasculitis, infection, trauma, vascular abnormalities, tumours, and non-tumoural masses. In this review, we summarise the magnetic resonance imaging findings for various pathological conditions that cause deterioration in visual acuity.

Diagnostic performance of zero-TE lung MR imaging in FDG PET/MRI for pulmonary malignancies.

OBJECTIVES: This study aimed to evaluate the diagnostic performance of the lung zero-echo time (ZTE) sequence in FDG PET/MRI for detection and differentiation of lung lesions in oncologic patients in comparison with conventional two-point Dixon-based MR imaging. METHODS: In this single-institution retrospective study approved by the institutional review board, 209 patients with malignancies (97 men and 112 women; age range, 17-89 years; mean age, 66.5 ± 12.9 years) underwent 18F-FDG PET/MRI between August 2017 and August 2018, with diagnostic Dixon and ZTE under respiratory gating acquired simultaneously with PET. Image analysis was performed for PET/Dixon and PET/ZTE fused images by two readers to assess the detectability and differentiation of lung lesions. The reference standard was pathological findings and/or the data from a chest CT. The detection and differentiation abilities were evaluated for all lesions and subgroups divided by lesion size and maximum standardized uptake value (SUVmax). RESULTS: Based on the reference standard, 227 lung lesions were identified in 113 patients. The detectability of PET/ZTE was significantly better than that of PET/Dixon for overall lesions, lesions with a SUVmax less than 3.0 and lesions smaller than 4 mm (p < 0.01). The diagnostic performance of PET/ZTE was significantly better than that of PET/Dixon for overall lesions and lesions smaller than 4 mm (p < 0.01). CONCLUSIONS: ZTE can improve diagnostic performance in the detection and differentiation of both FDG-avid and non-FDG-avid lung lesions smaller than 4 mm in size, yielding a promising tool to enhance the utility of FDG PET/MRI in oncology patients with lung lesions. KEY POINTS: • The detection rate of PET/ZTE for lesions with a SUVmax of less than 1.0 was significantly better than that of PET/Dixon. • The performance for differentiation of PET/ZTE for lesions that were even smaller than 4 mm in size were significantly better than that of PET/Dixon. • Inter-rater agreement of PET/ZTE for the differentiation of lesions less than 4 mm in size was substantial and better than that of PET/Dixon.

Computed Diffusion-Weighted Imaging in Prostate Cancer: Basics, Advantages, Cautions, and Future Prospects.

Computed diffusion-weighted MRI is a recently proposed post-processing technique that produces b-value images from diffusion-weighted imaging (DWI), acquired using at least two different b-values. This article presents an argument for computed DWI for prostate cancer by viewing four aspects of DWI: fundamentals, image quality and diagnostic performance, computing procedures, and future uses.

Imaging findings in radiation therapy complications of the central nervous system.

Radiation therapy is a useful treatment for tumors and vascular malformations of the central nervous system. Radiation therapy is associated with complications, including leukoencephalopathy, radiation necrosis, vasculopathy, and optic neuropathy. Secondary tumors are also often seen long after radiation therapy. Secondary tumors are often benign tumors, such as hemangiomas and meningiomas, but sometimes malignant gliomas and soft tissue sarcomas emerge. We review the imaging findings of complications that may occur after brain radiation therapy.

Diffusion-Weighted Imaging Shows a False-Negative Finding for Bone Marrow Involvement on 18F-FDG PET/MRI in a Patient With Malignant Lymphoma After Blood Transfusion.

Iron overload is a major complication in blood transfusion procedures. This report presents a case of malignant lymphoma, in which the findings of bone marrow involvement were discordant between F-FDG PET imaging studies and MRI with diffusion-weighted imaging studies. In this case, the PET imaging studies were positive for malignant lymphoma, whereas the MRI studies were negative. Iron deposition in the reticuloendothelial system due to posttransfusion iron overload was considered to be the cause of the decrease in signal intensity on diffusion-weighted imaging, resulting in a false-negative finding on MRI.

Remote effects in the ipsilateral thalamus and/or contralateral cerebellar hemisphere using FDG PET in patients with brain tumors.

PURPOSE: To evaluate reduced metabolism in the ipsilateral thalamus (TH) and/or contralateral cerebellum (CE) according to tumor localization and cortical metabolism around the tumor in patients with brain tumors based on FDG uptake. METHODS: This study investigated 48 consecutive patients with solitary cerebral hemisphere parenchymal brain tumors who underwent PET/CT and MRI. Patients were divided into 4 groups (A: reduced uptake in ipsilateral TH and contralateral CE, B: reduced uptake in ipsilateral TH only, C: reduced uptake in contralateral CE only, and D: no reduced uptake in ipsilateral TH or contralateral CE). FDG uptake and MRI findings were compared among these groups. RESULTS: Of 48 patients, group A included 24 (50%), group B included 10 (21%), group C included 0, and group D included 14 (29%). No significant tendencies were observed between the groups regarding tumor localization. However, reduced cortical metabolism around the tumor was observed in 22 patients in group A, 7 patients in group B, and 1 patient in group D. All patients in group B showed reduced metabolism from around the tumor up to the ipsilateral TH. CONCLUSION: Reduced FDG uptake in ipsilateral TH and contralateral CE usually occur simultaneously in patients with solitary brain tumors.

The safety and efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel in the treatment of non-small cell lung cancer patients with interstitial lung disease.

BACKGROUND: The optimal chemotherapy regimen for non-small cell lung cancer patients with interstitial lung disease is unclear. We therefore investigated the safety and efficacy of carboplatin plus nab-paclitaxel as a first-line regimen for non-small cell lung cancer in patients with interstitial lung disease. METHODS: We retrospectively reviewed advanced non-small cell lung cancer patients with interstitial lung disease who received carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen at Hyogo Cancer Center between February 2013 and August 2016. interstitial lung disease was diagnosed according to the findings of pretreatment chest high-resolution computed tomography. RESULTS: Twelve patients were included (male, n = 11; female, n = 1). The overall response rate was 67% and the disease control rate was 100%. The median progression free survival was 5.1 months (95% CI: 2.9-8.3 months) and the median overall survival was 14.9 months (95% CI: 4.8-not reached). A chemotherapy-related acute exacerbation of interstitial lung disease was observed in one patient; the extent of this event was Grade 2. There were no treatment-related deaths. CONCLUSIONS: Carboplatin plus nab-paclitaxel, as a first-line chemotherapy regimen for non-small cell lung cancer, showed favorable efficacy and safety in patients with preexisting interstitial lung disease.

Serial Assessment of Therapeutic Response to a New Radiosensitization Treatment, Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), in Patients with Stage I/II Breast Cancer Using Breast Contrast-Enhanced Magnetic Resonance Imaging.

BACKGROUND: We have developed a new radiosensitization treatment called Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II). Using KORTUC II, we performed breast-conserving treatment (BCT) without any surgical procedure for elderly patients with breast cancer in stages I/II or patients refusing surgery. Since surgery was not performed, histological confirmation of the primary tumor region following KORTUC II treatment was not possible. Therefore, to precisely evaluate the response to this new therapy, a detailed diagnostic procedure is needed. The goal of this study was to evaluate the therapeutic response to KORTUC II treatment in patients with stage I/II breast cancer using annual breast contrast-enhanced (CE) magnetic resonance imaging (MRI). METHODS: Twenty-one patients with stage I/II breast cancer who were elderly and/or refused surgery were enrolled in this study. All patients underwent MRI prior to and at 3 to 6 months after KORTUC II, and then approximately biannually thereafter. Findings from MRI were compared with those from other diagnostic modalities performed during the same time period. RESULTS: KORTUC II was well tolerated, with minimal adverse effects. All of 21 patients showed a clinically complete response (cCR) on CE MRI. The mean period taken to confirm cCR on the breast CE MRI was approximately 14 months. The mean follow-up period for the patients was 61.9 months at the end of October 2014. CONCLUSIONS: The therapeutic effect of BCT using KORTUC II without surgery could be evaluated by biannual CE MRI evaluations. Approximately 14 months were required to achieve cCR in response to this therapy.

Non-Surgical Breast-Conserving Treatment (KORTUC-BCT) Using a New Radiosensitization Method (KORTUC II) for Patients with Stage I or II Breast Cancer.

The purpose of the present study was to establish a non-surgical breast-conserving treatment (BCT) using KORTUC II radiosensitization treatment. A new radiosensitizing agent containing 0.5% hydrogen peroxide and 0.83% sodium hyaluronate (a CD44 ligand) has been developed for intra-tumoral injection into various tumors. This new method, named KORTUC II, was approved by our local ethics committee for the treatment of breast cancer and metastatic lymph nodes. A total of 72 early-stage breast cancer patients (stage 0, 1 patient; stage I, 23; stage II, 48) were enrolled in the KORTUC II trial after providing fully informed consent. The mean age of the patients was 59.7 years. A maximum of 6 mL (usually 3 mL for tumors of less than approximately 3 cm in diameter) of the agent was injected into breast tumor tissue twice a week under ultrasonographic guidance. For radiotherapy, hypofraction radiotherapy was administered using a tangential fields approach including an ipsilateral axillary region and field-in-field method; the energy level was 4 MV, and the total radiation dose was 44 Gy administered as 2.75 Gy/fraction. An electron boost of 3 Gy was added three times. Treatment was well tolerated with minimal adverse effects in all 72 patients. No patients showed any significant complications other than mild dermatitis. A total of 24 patients under 75 years old with stage II breast cancer underwent induction chemotherapy (EC and/or taxane) prior to KORTUC II treatment, and 58 patients with estrogen receptor-positive tumors also received hormonal therapy following KORTUC II. The mean duration of follow-up as of the end of September 2014 was 51.1 months, at which time 68 patients were alive without any distant metastases. Only one patient had local recurrence and died of cardiac failure at 6.5 years. Another one patient had bone metastases. For two of the 72 patients, follow-up ended after several months following KORTUC II treatment. In conclusion, non-surgical BCT can be performed using KORTUC II, which has three major characteristics: imaging guidance; enzyme-targeting; and targeting of breast cancer stem cells via the CD44 receptor.

Reduction of fibroproliferative changes in irradiated rat lung with soluble transforming growth factor-ß receptor.

The present study investigated whether established fibroproliferative changes in the irradiated rat lung are histopathologically reduced by an adenovirus­mediated soluble transforming growth factor (TGF)­ß type II receptor. Replication­defective adenoviral vectors expressing a type II human TGF­ß receptor (AdTß­ExR) were prepared. Male Fisher­344 rats were divided into the C, R and R + T groups. The rats in the C group did not receive irradiation or treatment. The rats in the R and R + T group each received 30 Gy irradiation to the right lung. Eight weeks following irradiation, the rats in the R and R + T group were treated with saline or AdTß­ExR, respectively. To analyze the TGF­ß expression, myofibroblast proliferation and macrophage/monocyte infiltration, sections of the lung were immunohistochemically stained at 16 weeks following irradiation. Silver staining was performed for semi­quantitative evaluation of the fibroproliferative changes. Definitive TGF­ß expression, myofibroblast proliferation and macrophage/monocyte infiltration were observed in the lungs of the R group, but were significantly lower in the lungs of the R + T group. With respect to the fibroproliferative changes, the proportion of red­stained areas in the R + T group was markedly lower than that in the R group. These data indicate that fibroproliferative changes induced by radiation are reversible and that TGF­ß has a critical role in fibroproliferative changes in the irradiated lung. The present results suggest that gene therapy with an adenoviral vector expressing a soluble TGF­ß receptor may be effective in reducing the established pulmonary fibrosis caused by radiation.