The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.

/pdf/fdg-pet-ct-eanm-procedure-guidelines-for-tumour-imaging-1ha0r3ck8g.pdf

FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0

Purpose Response Evaluation Criteria in Solid Tumors (RECIST) are insensitive in evaluating gastrointestinal stromal tumors (GISTs) treated with imatinib. This study evaluates whether computed tomography (CT) findings of GIST after imatinib treatment correlate with tumor responses by [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and develops reliable, quantitative, CT response criteria. Patients and Methods A total of 172 lesions selected by RECIST were evaluated in 40 patients with metastatic GISTs treated with imatinib. All patients had pretreatment and 2-month follow-up CTs and FDG-PETs. Multivariate analysis was performed using tumor size and density (Hounsfield unit [HU]) on CT and maximum standardized uptake value (SUVmax) on FDG-PET. Patients were observed up to 28 months. Results Mean baseline tumor size and density on CT were 5.3 cm and 72.8 HU, respectively, and mean baseline SUVmax on FDG-PET was 5.8. Thirty-three patients had good response on FDG-PET. A decrease in tumor siz...

Correlation of Computed Tomography and Positron Emission Tomography in Patients With Metastatic Gastrointestinal Stromal Tumor Treated at a Single Institution With Imatinib Mesylate: Proposal of New Computed Tomography Response Criteria

Once a poorly defined pathologic oddity, in recent years, gastrointestinal stromal tumor (GIST) has emerged as a distinct oncogenetic entity that is now center stage in clinical trials of kinase-targeted therapies. This review charts the rapid progress that has established GIST as a model for understanding the role of oncogenic kinase mutations in human tumorigenesis. Approximately 80% to 85% of GISTs harbor activating mutations of the KIT tyrosine kinase. In a series of 322 GISTs (including 140 previously published cases) studied by the authors in detail, mutations in the KIT gene occurred with decreasing frequency in exons 11 (66.1%), 9 (13%), 13 (1.2%), and 17 (0.6%). In the same series, a subset of tumors had mutations in the KIT-related kinase gene PDGF receptor alpha (PDGFRA), which occurred in either exon 18 (5.6%) or 12 (1.5%). The remainder of GISTs (12%) were wild type for both KIT and PDGFRA. Comparative studies of KIT-mutant, PDGFRA-mutant, and wild-type GISTs indicate that there are many similarities between these groups of tumors but also important differences. In particular, the responsiveness of GISTs to treatment with the kinase inhibitor imatinib varies substantially depending on the exonic location of the KIT or PDGFRA mutation. Given these differences, which have implications both for the diagnosis and treatment of GISTs, we propose a molecular-based classification of GIST. Recent studies of familial GIST, pediatric GIST, and variant forms of GIST related to Carney's triad and neurofibromatosis type 1 are discussed in relationship to this molecular classification. In addition, the role of mutation screening in KIT and PDGFRA as a diagnostic and prognostic aid is emphasized in this review.

Biology of gastrointestinal stromal tumors.

Sunitinib (SU011248) is an oral small molecular tyrosine kinase inhibitor that exhibits potent antiangiogenic and antitumor activity. Tyrosine kinase inhibitors such as SU6668 and SU5416 (semaxanib) demonstrated poor pharmacologic properties and limited efficacy; therefore, sunitinib was rationally designed and chosen for its high bioavailability and its nanomolar-range potency against the antiangiogenic receptor tyrosine kinases (RTKs)--vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR). Sunitinib inhibits other tyrosine kinases including, KIT, FLT3, colony-stimulating factor 1 (CSF-1), and RET, which are involved in a number of malignancies including small-cell lung cancer, GI stromal tumors (GISTs), breast cancer, acute myelogenous leukemia, multiple endocrine neoplasia types 2A and 2B, and familial medullary thyroid carcinoma. Sunitinib demonstrated robust antitumor activity in preclinical studies resulting not only in tumor growth inhibition, but tumor regression in models of colon cancer, non-small-cell lung cancer, melanoma, renal carcinoma, and squamous cell carcinoma, which were associated with inhibition of VEGFR and PDGFR phosphorylation. Clinical activity was demonstrated in neuroendocrine, colon, and breast cancers in phase II studies, whereas definitive efficacy has been demonstrated in advanced renal cell carcinoma and in imatinib-refractory GISTs, leading to US Food and Drug Administration approval of sunitinib for treatment of these two diseases. Studies investigating sunitinib alone in various tumor types and in combination with chemotherapy are ongoing. The clinical benchmarking of this small-molecule inhibitor of members of the split-kinase domain family of RTKs will lead to additional insights regarding the biology, potential biomarkers, and clinical utility of agents that target multiple signaling pathways in tumor, stromal, and endothelial compartments.

Sunitinib: From Rational Design to Clinical Efficacy

The recent introduction of high-resolution molecular imaging technology is considered by many experts as a major breakthrough that will potentially lead to a revolutionary paradigm shift in health care and revolutionize clinical practice. This paper intends to balance the capabilities of the two major molecular imaging modalities used in nuclear medicine, namely positron emission tomography (PET) and single photon emission computed tomography (SPECT). The motivations are many-fold: (1) to gain a better understanding of the strengths and limitations of the two imaging modalities in the context of recent and ongoing developments in hardware and software design; (2) to emphasize that certain issues, historically and commonly thought as limitations of one technology, may now instead be viewed as challenges that can be addressed; (3) to point out that current state of the art PET and SPECT scanners can (greatly) benefit from improvements in innovative image reconstruction algorithms; and (4) to identify important areas of research in PET and SPECT imaging that will be instrumental to further improvements in the two modalities. Both technologies are poised to advance molecular imaging and have a direct impact on clinical and research practice to influence the future of molecular medicine.

PET versus SPECT: strengths, limitations and challenges

More than 90% of gastrointestinal stromal tumors (GISTs) express the receptor tyrosine kinase KIT, and activating mutations of the KIT gene are detectable in the vast majority of these tumors. Imatinib mesylate (formerly STI571) is a potent inhibitor of KIT kinase activity and has been proven to be highly active in patients with unresectable or metastatic GIST expressing immunohistochemically detectable KIT protein. Here we report a patient with metastatic GIST who responded well to imatinib mesylate treatment despite the near absence of KIT expression in two different samples of his tumor. The tumor was morphologically typical for a GIST, stained positively for CD34, and harbored an in-frame deletion (WK 557–558) in KIT exon 11 that is common in GISTs. Our experience with this patient suggests that even GISTs with very low levels of KIT expression may respond to imatinib mesylate therapy.

Response to imatinib mesylate of a gastrointestinal stromal tumor with very low expression of KIT

This study was implemented to compare the value of PET, CT, and dual-modality PET/CT imaging for assessing gastrointestinal stromal tumor (GIST) response to imatinib therapy. Methods: Twenty patients with histologically proven GIST underwent 18F-FDG PET/CT imaging before and 1, 3, and 6 mo after the start of imatinib therapy. Separate PET and CT datasets, side-by-side PET and CT datasets, and fused PET/CT images were evaluated according to World Health Organization, Response Evaluation Criteria in Solid Tumors, and European Organisation for Research and Treatment of Cancer criteria for therapy response. Hounsfield units (HU) were assessed on CT images. A mean follow-up period of 381 ± 134 d served as the standard of reference. Results: The numbers of lesions detected in all patients were 135 with PET, 249 with CT, 279 on side-by-side evaluation, and 282 on fused PET/CT images. Tumor response was correctly characterized in 95% of patients after 1 mo and 100% after 3 and 6 mo with PET/CT. PET and CT images viewed side by side were correct in 90% of patients at 1 mo and 100% at 3 and 6 mo. PET accurately diagnosed tumor response in 85% of patients at 1 mo and 100% at 3 and 6 mo. CT was found to be accurate in 44% of patients at 1 mo, 60% at 3 mo, and 57% at 6 mo. HU were found to decrease by at least 25% in 12 of 14 responders after 1 mo. Conclusion: Tumor response to imatinib should be assessed with a combination of morphologic and functional imaging. Image fusion with combined PET/CT can provide additional information in individual cases when compared with side-by-side PET and CT.

https://jnm.snmjournals.org/content/jnumed/45/3/357.full.pdf

Comparison of PET, CT, and Dual-Modality PET/CT Imaging for Monitoring of Imatinib (STI571) Therapy in Patients with Gastrointestinal Stromal Tumors

The authors qualitatively and quantitatively assessed a solution containing 0.2% locust bean gum (LBG) and 2.5% mannitol (mannitol-LBG) dissolved in water to provide a negative oral contrast material in dual-modality positron emission tomography (PET)/computed tomography (CT) scanning. PET/CT was performed in 60 patients with cancer after oral administration of barium, water, or mannitol-LBG. Qualitative and quantitative analyses were conducted to determine bowel distention and a potential influence of the contrast agents on the PET data. Intestinal distention with mannitol-LBG proved superior to that with water or barium. Findings at both quantitative and qualitative analysis revealed apparently increased tracer uptake in the small bowel with barium in comparison to that with mannitol-LBG or water. Mannitol-LBG may, therefore, be used as a negative oral contrast agent at PET/CT scanning because it provides excellent bowel distention while avoiding contrast material-induced PET artifacts.

Dual-Modality PET/CT Scanning with Negative Oral Contrast Agent to Avoid Artifacts: Introduction and Evaluation

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Response to imatinib mesylate of a gastrointestinal stromal tumor with very low expression of KIT

Comparison of PET, CT, and Dual-Modality PET/CT Imaging for Monitoring of Imatinib (STI571) Therapy in Patients with Gastrointestinal Stromal Tumors

Dual-Modality PET/CT Scanning with Negative Oral Contrast Agent to Avoid Artifacts: Introduction and Evaluation