The purpose of this article is to review the status and limitations of anatomic tumor response metrics including the World Health Organization (WHO) criteria, the Response Evaluation Criteria in Solid Tumors (RECIST), and RECIST 1.1. This article also reviews qualitative and quantitative approaches to metabolic tumor response assessment with 18 F-FDG PET and proposes a draft framework for PET Response Criteria in Solid Tumors (PERCIST), version 1.0. Methods: PubMed searches, including searches for the terms RECIST, positron, WHO, FDG, cancer (in-cluding specific types), treatment response, region of interest, and derivative references, were performed. Abstracts and articles judged most relevant to the goals of this report were reviewed with emphasis on limitations and strengths of the anatomic and PET approaches to treatment response assessment. On the basis of these data and the authors' experience, draft criteria were formulated for PET tumor response to treatment.Results: Approximately 3,000 potentially relevant references were screened. Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria is widely applied but still has limitations in response assessments. For example, despite effective treatment, changes in tumor size can be minimal in tumors such as lymphomas, sarcoma, hepatomas, mesothelioma, and gastrointestinal stromal tumor. CT tumor density, contrast enhancement, or MRI characteristics appear more informative than size but are not yet routinely applied. RECIST criteria may show progression of tumor more slowly than WHO criteria. RECIST 1.1 criteria (assessing a maximum of 5 tumor foci, vs. 10 in RECIST) result in a higher complete response rate than the original RECIST criteria, at least in lymph nodes. Variability appears greater in assessing progression than in assessing response. Qualitative and quantitative approaches to 18 F-FDG PET response assessment have been applied and require a consistent PET methodology to allow quantitative assessments. Statistically significant changes in tumor standardized uptake value (SUV) occur in careful test-retest studies of high-SUV tumors, with a change of 20% in SUV of a region 1 cm or larger in diameter; however, medically relevant beneficial changes are often associated with a 30% or greater decline. The more extensive the therapy, the greater the decline in SUV with most effective treatments. Important components of the proposed PERCIST criteria include assessing normal reference tissue values in a 3-cm-diameter region of interest in the liver, using a consistent PET protocol, using a fixed small region of interest about 1 cm 3 in volume (1.2-cm diameter) in the most active region of metabolically active tumors to minimize statistical variability, assessing tumor size, treating SUV lean measurements in the 1 (up to 5 optional) most metabolically active tumor focus as a continuous variable, requiring a 30% decline in SUV for ''response,'' and deferring to RECIST 1.1 in cases that do not have 18 F-FDG avidity or are technically unsuitable...

The purpose of this study was to determine the reproducibility of dynamic contrast-enhanced (DCE)-MRI and compare quantitative kinetic parameters with semi-quantitative methods, and whole region-of-interest (ROI) with pixel analysis. Twenty-one patients with a range of tumour types underwent paired MRI examinations within a week, of which 16 pairs were evaluable. A proton density-weighted image was obtained prior to a dynamic series of 30 T 1 -weighted spoiled gradient echo images every 11.9 s with an intravenous bolus of gadopentetate dimeglumine given after the third baseline data point. Identical ROIs around the whole tumour and in skeletal muscle were drawn by the same observer on each pair of examinations and used for the reproducibility analysis. Semiquantitative parameters, gradient, enhancement and AUC (area under the curve) were derived from tissue enhancement curves. Quantitative parameters (K trans , k ep , v e ) were obtained by the application of the Tofts' model. Analysis was performed on data averaged across the whole ROI and on the median value from individual pixels within the ROI. No parameter showed a significant change between examinations. For all parameters except K trans , the variability was not dependent on the parameter value, so the absolute values for the size of changes needed for significance should be used for future reference rather than percentages. The size of change needed for significance in a group of 16 in tumours for K trans , k ep and v e was À14 to 16%, AE0.20 ml/ml/min (15%) and AE1.9 ml/ml (6%), respectively (pixel analysis), and À16 to 19%, AE0.23 ml/ml/min (16%) and AE1.9 ml/ml (6%) (whole ROI analysis). For a single tumour, changes greater than À45 to 83%, AE 0.78 ml/ml/min (60%) and AE 7.6 ml/ml (24%), respectively, would be significant (pixel analysis). For gradient, enhancement and AUC the size of change needed for significance in tumours was AE0.24 (17%), AE0.05 (6%) and AE0.06 (8%), respectively for a group of 16 (pixel analysis), and AE0.96 (68%), AE0.20 (25%) and AE0.22 (32%) for individuals. In muscle, the size of change needed for significance in a group of 16 for K trans , k ep and v e was À30 to 44%, AE0.81 ml/ml/min (61%) and AE1.7 ml/ml (13%). For gradient, enhancement and AUC it was AE0.09 (20%), AE0.02 (8%) and AE0.03 (12%). v e , enhancement and AUC are highly reproducible DCE-MRI parameters. K trans , k ep and gradient have greater variability, with larger changes in individuals required to be statistically significant, but are nevertheless sufficiently reproducible to detect changes greater than 14-17% in a cohort of 16 patients. Pixel analyses slightly improve reproducibility estimates and retain information about spatial heterogeneity. Reproducibility studies are recommended when treatment effects are being monitored.

Prostate-specific membrane antigen (PSMA) is a type II integral membrane protein expressed on the surface of prostate cancer (PCa) cells, particularly in androgen-independent, advanced, and metastatic disease. Previously, we demonstrated that N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-18F-fluorobenzyl-Lcysteine (18F-DCFBC) could image an experimental model of PSMA-positive PCa using PET. Here, we describe the initial clinical experience and radiation dosimetry of 18F-DCFBC in men with metastatic PCa. Methods Five patients with radiologic evidence of metastatic PCa were studied after the intravenous administration of 370 MBq (10 mCi) of 18F-DCFBC. Serial PET was performed until 2 h after administration. Time- activity curves were generated for selected normal tissues and metastatic foci. Radiation dose estimates were calculated using OLINDA/EXM 1.1. Results Most vascular organs demonstrated a slow decrease in radioactivity concentration over time consistent with clearance from the blood pool, with primarily urinary radiotracer excretion. Thirty-two PET-positive suspected metastatic sites were identified, with 21 concordant on both PET and conventional imaging for abnormal findings compatible with metastatic disease. Of the 11 PET-positive sites not identified on conventional imaging, most were within the bone and could be considered suggestive for the detection of early bone metastases, although further validation is needed. The highest mean absorbed dose per unit administered radioactivity (µGy/MBq) was in the bladder wall (32.4), and the resultant effective dose was 19.9 ± 1.34 µSv/MBq (mean ± SD). Conclusion Although further studies are needed for validation, our findings demonstrate the potential of 18F-DCFBC as a new positron-emitting imaging agent for the detection of metastatic PCa. This study also provides dose estimates for 18F-DCFBC that are comparable to those of other PET radiopharmaceuticals such as 18F-FDG.

CA4P acutely reduces Ktrans in human as well as rat tumors at well-tolerated doses, with no significant changes in kidney or muscle, providing proof of principle that this drug has tumor antivascular activity in rats and humans.

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