A case of pelvic squamous cell carcinoma of unknown primary origin that responded well to radiotherapy and nivolumab.

Squamous cell carcinoma of unknown primary origin in the pelvis is rare. We report a case of a 64-year-old woman with a large osteolytic squamous cell carcinoma of unknown primary origin in the pelvis that presented with p16 expression. The patient presented with leg pain and swelling and was admitted to our hospital. Computed tomography scans of the pelvis revealed a large osteolytic tumor. A computed tomography-guided needle biopsy was performed, and pathological examination revealed neoplastic cells with metastatic squamous cell carcinoma presenting with p16 expression. Despite a whole-body examination, tumor origin remained undetected. The patient was treated for this metastatic squamous cell carcinoma of unknown primary using palliative radiotherapy for hip pain and nivolumab. Remarkable reduction in the tumor marker levels and tumor size were obtained after therapy. Finally, partial remission and progression-free survival for more than 7 months were achieved. In conclusion, we experienced a rare case with a large p16-positive squamous cell carcinoma of unknown primary in pelvis, which responded well to radiotherapy and nivolumab.

SMARCA4-deficient tumors in the adrenal gland and small intestines: A rare case report.

Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs) are rare undifferentiated thoracic malignancies with poor prognosis. They predominantly affect young men who are heavy smokers. Recently, the category of SMARCA4-deficiency-related malignancy has been expanded to include extra-thoracic sites, such as the paranasal sinuses, gastrointestinal tract, ovary, and uterus. We report a rare case of SMARCA4-deficient tumors in the adrenal gland and small intestines. SMARCA4-deficient tumors should be included in the differential diagnosis when multiple large masses with heterogeneous contrast effect and strong accumulation are seen in cancers of unknown primary on 18F-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET/CT).

Process to Remove the Size Variants Contained in the Antibody-Chelator Complex PCTA-NCAB001 for Radiolabeling with Copper-64.

Understanding the physicochemical properties of antibody-drug conjugates is critical to assess their quality at manufacturing and monitor them during subsequent storage. For radiometal-antibody complexes, it is important to control the properties of the antibody-chelator conjugate to maintain the quality of the final product. We have been developing 64Cu-labeled anti-epidermal growth factor receptor antibody NCAB001 (64Cu-NCAB001) for the early diagnosis and therapy of pancreatic cancer with positron-emission tomography. Here, we characterized the larger size variants contained in the antibody-chelator conjugate PCTA-NCAB001 by multi-angle light scattering coupled with size-exclusion chromatography. Secondly, we developed a chromatographic method to remove these size variants. Lastly, we demonstrated the stability of PCTA-NCAB001 after the removal of size variants. Dimer and oligomers were identified in PCTA-NCAB001. These larger size variants, together with some smaller size variants, could be removed by hydrophobic interaction chromatography. The PCTA-NCAB001 product, after the removal of these size variants, could be stored at 4 °C for six months. The methods developed here can be applied to assure the quality of PCTA-NCAB001 and other antibody-drug conjugates to facilitate the development of antibody-radiometal conjugates for positron-emission tomography and radioimmunotherapy of malignant cancers.

Correlation between L-amino acid transporter 1 expression and 4-borono-2-18 F-fluoro-phenylalanine accumulation in humans.

BACKGROUND: The correlation between L-type amino acid transporter 1 (LAT1) expression and 4-borono-2-18 F-fluoro-phenylalanine (18 F-FBPA) accumulation in humans remains unclear. This study aimed to investigate the correlation between LAT1 expression in tumor tissues and 18 F-FBPA accumulation in patients with head and neck cancer who participated in a clinical trial of 18 F-FBPA positron emission tomography (PET). METHODS: Altogether, 28 patients with head and neck cancer who participated in a clinical trial of 18 F-FBPA PET at our institution between March 2012 and January 2018 were included. Correlations between standardized uptake values (SUVs); the maximum SUV (SUVmax ), the mean SUV within a 1 cm3 sphere centered at a single point, that is, the SUVmax (SUVpeak ), the minimum SUV (SUVmin ), and the intensity of LAT1 expression (maximum and minimum LAT1 expressions) were investigated. RESULTS: Weak correlations were identified between SUVmax and LAT1 maximum score, SUVmin and LAT1 maximum score, and SUVmin and LAT1 minimum score (ρ = 0.427, 0.362, and 0.330, respectively). SUVmax and LAT1 minimum score, SUVpeak and LAT1 maximum score, and SUVpeak and LAT1 minimum score demonstrated moderate correlations (ρ = 0.535, 0.556, and 0.661, respectively). Boron neutron capture therapy (BNCT) was performed in 2 of the 4 patients with discrepancies between 18 F-FBPA accumulation and intensity of LAT1 expression, and the intensity of LAT1 expression was a better predictor of treatment response. CONCLUSION: 18 F-FBPA accumulation and the intensity of LAT1 expression demonstrated a moderate correlation; however, LAT1 expression may be a better predictor of treatment response of BNCT in patients with discrepancies.

SAPHO syndrome with a purely osteolytic form: A case report.

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare, chronic autoinflammatory disorder that can present with a constellation of cutaneous and osteoarticular symptoms. Osteodestructive lesions are not pathognomonic, whereas hyperostosis and osteitis are the most prominent imaging findings. We report the case of a man with osteolytic changes of the lumbar vertebra and a history of palmoplantar pustulosis. Biopsy revealed no neoplasm, suggesting SAPHO syndrome. Our case demonstrates that knowledge of atypical radiologic findings is necessary for the diagnosis of SAPHO syndrome.

Fluorodeoxyglucose positron emission tomography (FDG/PET) shows the effect of carbon-ion radiotherapy (CIRT); with pathologic confirmation.

Response evaluation of carbon-ion radiotherapy poses a diagnostic challenge. Due to its functional aspects, fluorodeoxyglucose positron emission tomography (FDG/PET) has a role in the diagnosis of photon radiation therapy. In addition, several studies suggested that FDG/PET may be useful to select the optimal site for performing a diagnostic biopsy. Here, we report a 73-year-old female in which FDG/PET was effective in determining the recurrence of liposarcoma and the therapeutic effect. Based on the results of FDG/PET, we could make a pathologic definitive diagnosis and selectively performing carbon-ion radiotherapy for active tumors.

Trace Metal Impurities Effects on the Formation of [64Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) ([64Cu]Cu-ATSM).

[64Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) ([64Cu]Cu-ATSM) is a radioactive hypoxia-targeting therapeutic agent being investigated in clinical trials for malignant brain tumors. For the quality management of [64Cu]Cu-ATSM, understanding trace metal impurities' effects on the chelate formation of 64Cu and ATSM is important. In this study, we conducted coordination chemistry studies on metal-ATSM complexes. First, the effects of nonradioactive metal ions (Cu2+, Ni2+, Zn2+, and Fe2+) on the formation of [64Cu]Cu-ATSM were evaluated. When the amount of Cu2+ or Ni2+ added was 1.2 mol or 288 mol, equivalent to ATSM, the labeling yield of [64Cu]Cu-ATSM fell below 90%. Little effect was observed even when excess amounts of Zn2+ or Fe2+ were added to the ATSM. Second, these metals were reacted with ATSM, and chelate formation was measured using ultraviolet-visible (UV-Vis) absorption spectra. UV-Vis spectra showed a rapid formation of Cu2+ and the ATSM complex upon mixing. The rate of chelate formation by Ni2+ and ATSM was lower than that by Cu-ATSM. Zn2+ and Fe2+ showed much slower reactions with the ATSM than Ni2+. Trace amounts of Ni2+, Zn2+, and Fe2+ showed little effect on [64Cu]Cu-ATSM' quality, while the concentration of impurity Cu2+ must be controlled. These results can provide process management tools for radiopharmaceuticals.

Analyzing spatial distribution between 18F-fluorodeoxyglucose and 18F-boronophenylalanine positron emission tomography to investigate selection indicators for boron neutron capture therapy.

BACKGROUND: 18F-FDG PET is often utilized to determine BNCT selection due to the limited availability of 18F-BPA PET, which is performed by synthesizing 18F into the boron drug used for BNCT, although the uptake mechanisms between those are different. Additionally, only a few non-spatial point parameters, such as maximum SUV (SUVmax), have reported a correlation between those in previous studies. This study aimed to investigate the spatial accumulation pattern between those PET images in tumors, which would be expected to either show higher uptake on 18F-BPA PET or be utilized in clinical, to verify whether 18F-FDG PET could be used as a selection indicator for BNCT. METHODS: A total of 27 patients with 30 lesions (11 squamous cell carcinoma, 9 melanoma, and 10 rhabdomyosarcoma) who received 18F-FDG and 18F-BPA PET within 2 weeks were enrolled in this study. The ratio of metabolic tumor volumes (MTVs) to GTV, histogram indices (skewness/kurtosis), and the correlation of total lesion activity (TLA) and non-spatial point parameters (SUVmax, SUVpeak, SUVmin, maximum tumor-to-normal tissue ratio (Tmax/N), and Tmin/N) were evaluated. After local rigid registration between those images, distances of locations at SUVmax and the center of mass with MTVs on each image and similarity indices were also assessed along its coordinate. RESULTS: In addition to SUVmax, SUVpeak, and Tmax/N, significant correlations were found in TLA. The mean distance in SUVmax was [Formula: see text] and significantly longer than that in the center of mass with MTVs. The ratio of MTVs to GTV, skewness, and kurtosis were not significantly different. However, the similarities of MTVs were considerably low. The similarity indices of Dice similarity coefficient, Jaccard coefficient, and mean distance to agreement for MTV40 were [Formula: see text], [Formula: see text], and [Formula: see text] cm, respectively. Furthermore, it was worse in MTV50. In addition, spatial accumulation patterns varied in cancer types. CONCLUSIONS: Spatial accumulation patterns in tumors showed low similarity between 18F-FDG and 18F-BPA PET, although the various non-spatial point parameters were correlated. In addition, the spatial accumulation patterns were considerably different in cancer types. Therefore, the selection for BNCT using 18F-FDG PET should be compared carefully with using 18F-FBPA PET.

Preclinical Safety Evaluation of Intraperitoneally Administered Cu-Conjugated Anti-EGFR Antibody NCAB001 for the Early Diagnosis of Pancreatic Cancer Using PET.

Detecting tumor lesions <1 cm in size using current imaging methods remains a clinical challenge, especially in pancreatic cancer. Previously, we developed a method to identify pancreatic tumor lesions ≥3 mm using positron emission tomography (PET) with an intraperitoneally administered 64Cu-labeled anti-epidermal growth factor receptor (EGFR) antibody (64Cu-NCAB001 ipPET). Here, we conducted an extended single-dose toxicity study of 64Cu-NCAB001 ipPET in mice based on approach 1 of the current ICH M3 [R2] guideline, as our new drug formulation contains 45 µg of the antibody. We used NCAB001 labeled with stable copper isotope instead of 64Cu. The total content of size variants was approximately 6.0% throughout the study. The relative binding potency of Cu-NCAB001 to recombinant human EGFR was comparable to that of cetuximab. The general and neurological toxicities of Cu-NCAB001 ipPET at 62.5 or 625 µg/kg were assessed in mice. The no-observed-adverse-effect level of Cu-NCAB001 was 625 µg/kg, a dose approximately 1000-fold higher at the µg/kg level than the dose of 64Cu-NCAB001 in our formulation (45 µg). The size variants did not affect the safety of the formulation. Therefore, clinical studies on the efficacy of 64Cu-NCAB001 ipPET for early detection of pancreatic cancer using PET imaging can be safely conducted.

In Vitro Tumor Cell-Binding Assay to Select High-Binding Antibody and Predict Therapy Response for Personalized 64Cu-Intraperitoneal Radioimmunotherapy against Peritoneal Dissemination of Pancreatic Cancer: A Feasibility Study.

Peritoneal dissemination of pancreatic cancer has a poor prognosis. We have reported that intraperitoneal radioimmunotherapy using a 64Cu-labeled antibody (64Cu-ipRIT) is a promising adjuvant therapy option to prevent this complication. To achieve personalized 64Cu-ipRIT, we developed a new in vitro tumor cell-binding assay (64Cu-TuBA) system with a panel containing nine candidate 64Cu-labeled antibodies targeting seven antigens (EGFR, HER2, HER3, TfR, EpCAM, LAT1, and CD98), which are reportedly overexpressed in patients with pancreatic cancer. We investigated the feasibility of 64Cu-TuBA to select the highest-binding antibody for individual cancer cell lines and predict the treatment response in vivo for 64Cu-ipRIT. 64Cu-TuBA was performed using six human pancreatic cancer cell lines. For three cell lines, an in vivo treatment study was performed with 64Cu-ipRIT using high-, middle-, or low-binding antibodies in each peritoneal dissemination mouse model. The high-binding antibodies significantly prolonged survival in each mouse model, while low-and middle-binding antibodies were ineffective. There was a correlation between in vitro cell binding and in vivo therapeutic efficacy. Our findings suggest that 64Cu-TuBA can be used for patient selection to enable personalized 64Cu-ipRIT. Tumor cells isolated from surgically resected tumor tissues would be suitable for analysis with the 64Cu-TuBA system in future clinical studies.

Identification and quantitative structure-activity relationship assessment of trace chemical impurities contained in the therapeutic formulation of [64Cu]Cu-ATSM.

BACKGROUND: [64Cu]Cu-diacethyl-bis(N4-methylthiosemicarbazone) ([64Cu]Cu-ATSM) is a radioactive hypoxia-targeting therapeutic agent, and the efficacy and safety of [64Cu]Cu-ATSM in the treatment of malignant brain tumors are evaluated in clinical trials. For the clinical application of [64Cu]Cu-ATSM, we determined a drug formulation incorporating a stabilizer against radiolysis and confirmed its radiochemical stability. This study aimed to identify trace chemical impurities derived from the degradation of ATSM contained in the [64Cu]Cu-ATSM investigational drug formulation and assess their potential hazards by quantitative structure-activity relationship (QSAR) assessment. METHODS: We hypothesized that the chemical impurities contained in the [64Cu]Cu-ATSM formulation were derived from the degradation of ATSM. Therefore, we first identified the degradants of ATSM using LC-MS/MS. ATSM was dissolved with the drug formulation of [64Cu]Cu-ATSM, except for 64Cu, and analyzed by LC-MS/MS at 0 and 48 h after sample preparation. Subsequently, the chemical impurities contained in the [64Cu]Cu-ATSM formulation were measured at 0, 5, and 24 h after preparation by HPLC, and the results were compared to the degradants of ATSM. The potential hazards of the chemical impurities contained in the [64Cu]Cu-ATSM formulation were assessed using the QSAR Toolbox (ver. 4.3). RESULTS: Six ATSM degradants were detected and identified by LC-MS/MS analysis, indicating that the functional groups around the nitrogen and sulfur atoms of ATSM were affected. The same peaks were detected as trace chemical impurities in the [64Cu]Cu-ATSM formulation at 24 h, while no apparent peaks were detected at 0 and 5 h. The estimated LD50 values of these chemical impurities showed 4.31 mg/kg or more by QSAR assessment. In contrast, the estimated amount of each chemical impurity exposed to patients was 31.8 ng/kg or less per dose. The smallest margin between the amount of chemical impurities and smallest estimated LD50 value of the corresponding impurity was a ratio of approximately 1:700,000. CONCLUSIONS: We identified trace chemical impurities derived from ATSM in the [64Cu]Cu-ATSM formulation. This suggests that the potential risk of the systemic exposure of patients to these chemical impurities is substantially low.

Transitional changes of spacer materials used in carbon-ion radiation therapy.

PURPOSE: To evaluate the imaging findings and transitional changes in spacer materials used in carbon-ion radiation therapy MATERIALS: Medical records were retrospectively reviewed, and the maximum thickness, volume, and CT value of spacers were calculated from CT scans. Procedure-related complications were recorded. RESULTS: A spacer was surgically placed in six patients in retroperitoneal, presacral, or peritoneal sites. The spacer material was polyglycolic acid (PGA) in four patients and expanded polytetrafluoroethylene (ePTFE) in two patients. The thickness of PGA spacers showed no changes in any patients within 4 weeks, but increased within 6 weeks in one patient and was unchanged or decreased in the remaining patients. PGA spacer volume decreased gradually after placement in three of four patients; this was observed at 4 months in two patients and at 6 months in one patient. The mean CT value of PGA spacers was 83 HU just after placement, and decreased gradually thereafter. Air was seen in the PGA spacers of two patients. Neither ePTFE spacer showed volume changes over time, and the mean CT value was low (mean, -53.7 HU) just after placement but increased rapidly to 145 HU at 2 months. CONCLUSION: Spacer imaging findings may vary according to type and may change over time. Familiarity with these features is beneficial for diagnostic radiologists.

Preliminary experiences of PET/MRI in predicting complete response in patients with breast cancer treated with neoadjuvant chemotherapy.

Clinical response predictions through image examinations after neoadjuvant chemotherapy (NAC) for breast cancer is important. The present study aimed to evaluate the utility of a novel imaging modality, positron-emission tomography/magnetic resonance imaging (PET/MRI), in predicting the pathological complete response (pCR) to NAC in patients with early breast cancer. A total of 74 patients underwent PET/MRI, mammography (MG), including tomosynthesis, and ultrasound (US) after NAC. The complete response was predicted using each modality and these outcomes were compared accordingly. In terms of PET/MRI, complete response (CR) was defined as the disappearance of 18F-fluorodeoxyglucose uptake and the absence of enhanced lesions with contrast enhanced MRI. In MG and US, undetectable lesions were considered as CR. The background and tumor characteristics of patients were also analyzed between the pCR and non-pCR cases. Overall, 18 (24.3%) of the 74 patients achieved pCR. The overall sensitivity and specificity of PET/MRI were 72.2 and 78.6%, respectively. Both the sensitivity in hormone receptor (HR)-positive cases and the specificity in HR-negative cases were 100%. HR-negative and human epidermal growth factor receptor 2 (HER2)-positive cases demonstrated a significant association with pCR compared with HR-positive cases and triple negative cases (P=0.017). Furthermore, patients with 'mass' type lesions evaluated by MRI before NAC experienced pCR with a higher frequency than those with 'non-mass' type lesions. There was a statistically significant difference between the two groups (P=0.018). In conclusion, PET/MRI is a different diagnostic approach that utilizes a multi-modality system. It demonstrates reasonable diagnostic accuracies of the responses of NAC with reference to hormonal subtypes in breast cancer.

Evaluation of 64Cu-Labeled New Anti-EGFR Antibody NCAB001 with Intraperitoneal Injection for Early PET Diagnosis of Pancreatic Cancer in Orthotopic Tumor-Xenografted Mice and Nonhuman Primates.

OBJECTIVES: To improve the prognosis of pancreatic cancer, new imaging methods to identify tumor lesions at a size of <1 cm are urgently needed. To approach this clinical issue, we developed a new method to detect small tumor lesions in the pancreas (≥3 mm) by positron emission tomography (PET) using an intraperitoneally (ip)-administered 64Cu-labeled new anti-epidermal growth factor receptor (EGFR) antibody (encoded as NCAB001), called 64Cu-NCAB001 ipPET. METHODS: NCAB001 was manufactured under cGMP conditions and labeled with 64Cu. The radiochemical and biological properties of 64Cu-NCAB001 were evaluated. Tumor uptake of an ip-administered 64Cu-NCAB001 in mice with orthotopic pancreatic tumor xPA1-DC xenografts was also evaluated. Pharmacokinetics and radiation dosimetry were examined using PET images acquired after the ip administration of 64Cu-NCAB001 into cynomolgus monkeys with pharmacologic safety monitoring. RESULTS: Radio-chromatography, cell-binding assays, and biodistribution of 64Cu-NCAB001 in mice were identical to those of our previous data with clinically available cetuximab. Small tumor lesions in the pancreas (≥3 mm) of mice could be identified by 64Cu-NCAB001 ipPET. The ip administration of 64Cu-NCAB001 into monkeys was safely conducted using ultrasound imaging. PET images in monkeys showed that ip-administered 64Cu-NCAB001 was distributed throughout the intraperitoneal cavity for up to 6 h and cleared thereafter. Most of the radioactivity was distributed in the liver and the large intestine. The radioactivity around the pancreas became negligible 24 h after administration. The estimated human effective dose was 0.0174 mSv/MBq. CONCLUSION: Our data support the initiation of clinical trials of 64Cu-NCAB001 ipPET to transfer this promising tool for the early diagnosis of pancreatic cancers.

A case of bulla formation after treatment for COVID-19 pneumonia.

In December 2019, coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported in Wuhan, China. An 82-year-old woman presented to our hospital with high fever (39°C) and chest computed tomography revealed ground-glass opacities in the left lung apex. She was positive for SARS-CoV-2 based on a polymerase chain reaction test, and diagnosed with COVID-19 pneumonia. 6 months after treatment, chest CT showed a large bulla (47 mm × 29 mm) in the left lung apex, although pneumonia had partially resolved. Radiologic follow-up is needed after COVID-19 pneumonia, because patients may develop bullae after treatment.

Characterization and Stabilization of a New 64Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography.

Early diagnosis of pancreatic cancer using current imaging modalities remains challenging. We have developed a new approach to identify tumor lesions ≥ 3 mm in the pancreas by positron emission tomography (PET) with a new intraperitoneally administered 64Cu-labeled anti-epidermal growth factor receptor (EGFR) antibody (encoded as NCAB001), called 64Cu-NCAB001 ipPET. Generally, in clinical research, a radiometal-antibody complex must be prepared immediately before use at the imaging site. To make 64Cu-NCAB001 ipPET available to daily clinical practices in a sustainable way, the NCAB001-chelator conjugate and 64Cu-NCAB001 must be characterized and stabilized. NCAB001 was manufactured under cGMP conditions. NCAB001 was conjugated with a bifunctional chelator (p-SCN-Bn-PCTA), and the antibody-chelator conjugate (PCTA-NCAB001) was characterized by LC/MS and ELISA. Thereafter, to effectively manufacture 64Cu-NCAB001, we developed a new formulation to stabilize PCTA-NCAB001 and 64Cu-NCAB001. An average of three PCTA chelators were conjugated per molecule of NCAB001. The relative binding potency of PCTA-NCAB001 was comparable to cetuximab. The formulation consisting of acetate buffer, glycine, and polysorbate-80 stabilized PCTA-NCAB001 for a year-long storage. Additionally, this formulation enabled the stabilization of 64Cu-NCAB001 for up to 24 h after radiolabeling with a sufficient radioactivity concentration for clinical use. These results may accelerate the future use of 64Cu-NCAB001 ipPET in clinical settings for the early diagnosis and treatment of pancreatic cancer.

Transformation Scoring System (TSS): A new assessment index for clinical transformation of follicular lymphoma.

Although histologic analysis is the gold standard for diagnosing follicular lymphoma (FL) transformation, many patients are diagnosed with transformation by clinical factors as biopsy specimens often cannot be obtained. Despite the frequency of clinical diagnosis, no clinical assessment tool has yet been established for FL transformation in the rituximab era. We derived and validated a transformation scoring system (TSS) based on retrospective analyses of 126 patients with biopsy-proven FL and histologic transformation (HT) at two hospitals of the National Cancer Center of Japan. In the derivation set (76 patients), the detailed analyses of the clinical characteristics at disease progression showed that lactate dehydrogenase (LDH) elevation, focal lymph nodal (LN) enlargement, hemoglobin <12 g/dl, and poor performance status (PS) (2-4) were associated with HT. The weights of these variables were decided based on the regression coefficients. Next, we constructed a TSS encompassing the above four factors: LDH, (> upper limit of normal [ULN], ≤ULN ×2) (1 point), (≥ULN ×2) (2 points); focal LN enlargement, (≥3 cm, <7 cm) (1 point), (≥7 cm) (2 points); hemoglobin <12 g/dl (1 point); poor PS (2 points). We identified a high positive predictive value (PPV) (96.4%) and negative predictive value (NPV) (85.4%) for diagnosing HT when a cutoff score of 2 was selected for our TSS. In an external validation set (50 patients), the probability of HT was high with scores ≥2 (PPV, 93.3%; NPV, 82.9%). We developed a TSS that offers a simple, yet, valuable tool, for diagnosing HT, especially in patients who cannot undergo biopsy.

Usefulness of carbon-11-labeled methionine positron-emission tomography for assessing the treatment response of primary central nervous system lymphoma.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) responds relatively quickly to chemotherapy or radiotherapy. However, determination of a complete response after treatment is often difficult because of extremely light residual contrast enhancement on magnetic resonance images due to the effects of microhemorrhages and scar tissue formation. These small enhancing lesions define an unconfirmed complete response. The aim of this study was to investigate the usefulness of carbon-11-labeled methionine (11C-Met) positron-emission tomography (PET) for determining the treatment response of PCNSL. METHODS: Data for 36 patients who were treated for PCNSL between 2011 and 2015 and underwent magnetic resonance imaging and 11C-Met PET were reviewed. Magnetic resonance imaging findings were classified as complete response, unconfirmed complete response, and tumor mass (a composite of partial response, stable disease and progressive disease). PET images were evaluated, standardized uptake values were quantified, and the tumor-to-normal tissue count ratio (TNR) was calculated. Receiver operating characteristic curves were generated to determine the optimal cutoff TNRs. RESULTS: The optimal TNRs for differentiating complete response and unconfirmed complete response from tumor mass were 1.83 (area under the curve, 0.951) and 1.80 (area under the curve, 0.932), respectively. The corresponding sensitivity and specificity values for the diagnosis of tumor mass were 82.4 and 100%, respectively, in the complete response group and 85.3 and 85%, respectively, in the unconfirmed complete response group. CONCLUSIONS: A TNR of ≥1.80 can aid in the detection of active PCNSL using 11C-Met PET. Thus, 11C-Met-PET may be a useful tool for accurate evaluation of the treatment efficacy in PCNSL.

Comparison of 18FBPA uptake with 18FDG uptake in cancer patients.

For the patients who underwent 18fluorinated para-boronophenylalanine (18FBPA) positron emission tomography (PET) and 18fluorodeoxyglucose (18FDG) PET within a period of 2 weeks, maximum standardized uptake value (SUVmax), tumor-to-normal tissue ratio (TNR), and tumor-to-blood ratio (TBR) for 18FBPA were compared with SUVmax for 18FDG. A total of 30 patients were selected for comparison. SUVmax for 18FBPA was correlated the best with SUVmax for 18FDG. Subsequently, the SUVmax correlation between 18FBPA and 18FDG were verified among 82 patients. The correlation factor was 0.4825.