Camila Mosci

Combined 18F-Fluoride and 18F-FDG PET/CT Scanning for Evaluation of Malignancy: Results of an International Multicenter Trial

18F-FDG PET/CT is used in a variety of cancers, but because of variable rates of glucose metabolism, not all cancers are reliably identified. 18F− PET/CT allows for the acquisition of highly sensitive and specific images of the skeleton. We prospectively evaluated combined 18F−/18F-FDG as a single PET/CT examination for evaluation of cancer patients and compared it with separate 18F− PET/CT and 18F-FDG PET/CT scans. Methods: One hundred fifteen participants with cancer were prospectively enrolled in an international multicenter trial evaluating 18F− PET/CT, 18F-FDG PET/CT, and combined 18F−/18F-FDG PET/CT. The 3 PET/CT scans were performed sequentially within 4 wk of one another for each patient. Results: 18F−/18F-FDG PET/CT allowed for accurate interpretation of radiotracer uptake outside the skeleton, with findings similar to those of 18F-FDG PET/CT. In 19 participants, skeletal disease was more extensive on 18F− PET/CT and 18F−/18F-FDG PET/CT than on 18F-FDG PET/CT. In another 29 participants, 18F− PET/CT and 18F−/18F-FDG PET/CT showed osseous metastases where 18F-FDG PET/CT was negative. The extent of skeletal lesions was similar in 18 participants on all 3 scans. Conclusion: This trial demonstrated that combined 18F−/18F-FDG PET/CT shows promising results when compared with separate 18F− PET/CT and 18F-FDG PET/CT for evaluation of cancer patients. This result opens the possibility for improved patient care and reduction in health-care costs, as will be further evaluated in future trials.

Prospective Comparison of 99mTc-MDP Scintigraphy, Combined 18F-NaF and 18F-FDG PET/CT, and Whole-Body MRI in Patients with Breast and Prostate Cancer

We prospectively evaluated the use of combined 18F-NaF/18F-FDG PET/CT in patients with breast and prostate cancer and compared the results with those for 99mTc-MDP bone scintigraphy and whole-body MRI. Methods: Thirty patients (15 women with breast cancer and 15 men with prostate cancer) referred for standard-of-care bone scintigraphy were prospectively enrolled in this study. 18F-NaF/18F-FDG PET/CT and whole-body MRI were performed after bone scintigraphy. The whole-body MRI protocol consisted of both unenhanced and contrast-enhanced sequences. Lesions detected with each test were tabulated, and the results were compared. Results: For extraskeletal lesions, 18F-NaF/18F-FDG PET/CT and whole-body MRI had no statistically significant differences in sensitivity (92.9% vs. 92.9%, P = 1.00), positive predictive value (81.3% vs. 86.7%, P = 0.68), or accuracy (76.5% vs. 82.4%, P = 0.56). However, 18F-NaF/18F-FDG PET/CT showed significantly higher sensitivity and accuracy than whole-body MRI (96.2% vs. 81.4%, P < 0.001, 89.8% vs. 74.7%, P = 0.01) and bone scintigraphy (96.2% vs. 64.6%, P < 0.001, 89.8% vs. 65.9%, P < 0.001) for the detection of skeletal lesions. Overall, 18F-NaF/18F-FDG PET/CT showed higher sensitivity and accuracy than whole-body MRI (95.7% vs. 83.3%, P < 0.002, 87.6% vs. 76.0%, P < 0.02) but not statistically significantly so when compared with a combination of whole-body MRI and bone scintigraphy (95.7% vs. 91.6%, P = 0.17, 87.6% vs. 83.0%, P = 0.53). 18F-NaF/18F-FDG PET/CT showed no significant difference from a combination of 18F-NaF/18F-FDG PET/CT and whole-body MRI. No statistically significant differences in positive predictive value were noted among the 3 examinations. Conclusion: 18F-NaF/18F-FDG PET/CT is superior to whole-body MRI and 99mTc-MDP scintigraphy for evaluation of skeletal disease extent. Further, 18F-NaF/18F-FDG PET/CT and whole-body MRI detected extraskeletal disease that may change the management of these patients. 18F-NaF/18F-FDG PET/CT provides diagnostic ability similar to that of a combination of whole-body MRI and bone scintigraphy in patients with breast and prostate cancer. Larger cohorts are needed to confirm these preliminary findings, ideally using the newly introduced simultaneous PET/MRI scanners.

18F-FPPRGD2 PET/CT: Pilot Phase Evaluation of Breast Cancer Patients

PURPOSE To present data from the first prospective pilot phase trial of breast cancer participants imaged with fluorine 18 ((18)F)-2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid ( RGD arginine-glycine-aspartic acid ) peptide (PEG3-E[c{ RGD arginine-glycine-aspartic acid yk}]2) ( FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) ), a radiopharmaceutical agent used in positron emission tomographic (PET) imaging. MATERIALS AND METHODS The local institutional review board approved the HIPAA-compliant protocol. Written informed consent was obtained from each patient. Eight women (age range, 44-67 years; mean age, 54.3 years ± 8.8 [standard deviation]) with newly diagnosed or recurrent breast cancer were recruited between November 2010 and February 2011. (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) PET/computed tomographic (CT) and (18)F-fluorodeoxyglucose ( FDG fluorine 18 fluorodeoxyglucose ) PET/CT examinations were performed within 3 weeks of each other. Dynamic (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) PET and two whole-body static (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) PET/CT scans were obtained. During this time, vital signs and electrocardiograms were recorded at regular intervals. Blood samples were obtained before the injection of (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) and at 24 hours and 1 week after injection to evaluate for toxicity. A nonparametric version of multivariate analysis of variance was used to assess the safety outcome measures simultaneously across time points. A paired two-sample t test was performed to compare the maximum standardized uptake values ( SUVmax maximum standardized uptake value ). RESULTS (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) was well tolerated, without noticeable changes in vital signs, on electrocardiograms, or in laboratory values. A total of 30 lesions were evaluated at (18)F- FDG fluorine 18 fluorodeoxyglucose PET/CT and (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) PET/CT. The primary breast lesions had (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) uptake with SUVmax maximum standardized uptake value of 2.4-9.4 (mean, 5.6 ± 2.8) 60 minutes after injection, compared with (18)F- FDG fluorine 18 fluorodeoxyglucose uptake with SUVmax maximum standardized uptake value of 2.8-18.6 (mean, 10.4 ± 7.2). Metastatic lesions also showed (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) uptake, with SUVmax maximum standardized uptake value of 2.4-9.7 (mean, 5.0 ± 2.3) at 60 minutes, compared with (18)F- FDG fluorine 18 fluorodeoxyglucose uptake with SUVmax maximum standardized uptake value of 2.2-14.6 (mean, 6.6 ± 4.2). CONCLUSION Data from this pilot phase study suggest that (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) is a safe PET radiopharmaceutical agent. Evaluation of (18)F- FPPRGD2 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (PEG3-E[c{RGDyk}]2) in participants with breast cancer demonstrated significant uptake in the primary lesion and in the metastases. Larger cohorts are required to confirm these preliminary findings.

PET/CT imaging of thyroid cancer.

Positron emission tomography (PET) is a highly sensitive, low invasive technology for cancer biology imaging. The role of F-18 FDG PET/CT in differentiated thyroid cancer (DTC) is well established, particularly in patients presenting with elevated Tg levels and negative radioactive iodine WBS. It has been demonstrated that F-18 FDG uptake represents less differentiated thyroid cancer cells or dedifferentiated cells and PET positive lesions are more likely to be resistant to 131I treatment. The uptake of F-18 FDG is related to tumor size, thyroid capsule invasion and histological variants with a poor prognosis. As in other cancers, early detection of recurrences improves outcomes and survival. 124I PET/CT can also be used to image the patients with DTC, similarly to 123I WBS. Compared with F-18 FDG PET/CT, its spatial resolution is only slightly degraded but increasing the imaging time reduces this difference. In addition, F-18 FDG PET/CT has been found helpful in the management of patients with anaplastic and medullary thyroid cancer. Other radiopharmaceuticals such as 68Ga-DOTATOC and F-18 DOPA may provide complimentary information to F-18 FDG PET/CT in the detection of recurrent thyroid cancer.

(18)F-FDG PET/CT in the management of patients with post-transplant lymphoproliferative disorder.

ObjectivesPost-transplant lymphoproliferative disorder (PTLD) is a rare but serious complication in transplant patients. Although fluorine-18 2-fluoro-2-deoxyglucose PET and computed tomography (18F-FDG PET/CT) has been used for the evaluation and management of patients with PTLD, its utility has yet to be documented. We were therefore prompted to review our experience with 18F-FDG PET/CT in PTLD. Materials and methodsWe retrospectively reviewed the records of consecutive patients who had undergone 18F-FDG PET/CT for evaluation of PTLD from January 2004 to June 2012 at our institution. 18F-FDG PET/CT scans were compared with other imaging modalities performed concurrently. A chart review of pertinent clinical information was also conducted. ResultsA total of 30 patients were identified (14 female and 16 male; 1.7–76.7 years of age, average: 23.8 years). Twenty-seven participants had biopsy-proven PTLD and another three had been treated for PTLD because of high clinical suspicion of disease and positive 18F-FDG PET/CT findings in the absence of histological diagnosis. Eighty-three percent of these PTLD patients had extranodal involvement. In 57% of the cases, 18F-FDG PET/CT detected occult lesions not identified on other imaging modalities or suggested PTLD in equivocal lesions. The more aggressive PTLD histological subtypes demonstrated higher SUVmax compared with the less aggressive subtypes. Conclusion18F-FDG PET/CT is beneficial in the diagnostic evaluation of patients with PTLD. 18F-FDG PET/CT has the ability to detect occult lesions not identified on other imaging modalities, particularly extranodal lesions. In addition, 18F-FDG PET/CT may predict the PTLD subtype, as the lesions with higher pathologic grade presented with significantly higher SUVmax compared with the less aggressive forms.

Glioblastoma Multiforme Recurrence: An Exploratory Study of 18F FPPRGD2 PET/CT

PURPOSE To prospectively evaluate fluorine 18 ((18)F) 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) (FPPRGD2) positron emission tomography (PET) in patients with glioblastoma multiforme (GBM). MATERIALS AND METHODS The institutional review board approved this HIPAA-compliant protocol. Written informed consent was obtained from each patient. (18)F FPPRGD2 uptake was measured semiquantitatively in the form of maximum standardized uptake values (SUV(max)) and uptake volumes before and after treatment with bevacizumab. Vital signs and laboratory results were collected before, during, and after the examinations. A nonparametric version of multivariate analysis of variance was used to assess safety outcome measures simultaneously across time points. A paired two-sample t test was performed to compare SUV(max). RESULTS A total of 17 participants (eight men, nine women; age range, 25-65 years) were enrolled prospectively. (18)F FPPRGD2 PET/computed tomography (CT), (18)F fluorodeoxyglucose (FDG) PET/CT, and brain magnetic resonance (MR) imaging were performed within 3 weeks, prior to the start of bevacizumab therapy. In eight of the 17 patients (47%), (18)F FPPRGD2 PET/CT was repeated 1 week after the start of bevacizumab therapy; six patients (35%) underwent (18)F FPPRGD2 PET/CT a third time 6 weeks after starting bevacizumab therapy. There were no changes in vital signs, electrocardiographic findings, or laboratory values that qualified as adverse events. One patient (6%) had recurrent GBM identified only on (18)F FPPRGD2 PET images, and subsequent MR images enabled confirmation of recurrence. Of the 17 patients, 14 (82%) had recurrent GBM identified on (18)F FPPRGD2 PET and brain MR images, while (18)F FDG PET enabled identification of recurrence in 13 (76%) patients. Two patients (12%) had no recurrent GBM. CONCLUSION (18)F FPPRGD2 is a safe PET radiopharmaceutical that has increased uptake in GBM lesions. Larger cohorts are required to confirm these preliminary findings.

18F-sodium fluoride PET/CT in oncology: an atlas of SUVs.

Purpose The purpose of this study was to analyze the distribution of 18F Sodium Fluoride (18F-NaF) uptake in the normal skeleton, benign and malignant bone lesions, and extraskeletal tissues, using semiquantitative SUV measurements. Patients and Methods We retrospectively analyzed data from 129 patients who had 18F-NaF PET/CT at our institution for an oncological diagnosis between 2007 and 2014. There were 99 men and 30 women, 19 to 90 years old (mean [SD], 61.5 [15.5]). The range, average, and SD of SUV were measured for normal bone and extraskeletal tissues uptake for the entire patient population. A separate statistical analysis was performed to compare group A, which corresponds to the population of patient with no 18F-NaF–avid metastatic lesions, and group B, which corresponds to the population of patient with 18F-NaF–avid metastatic lesions. We also measured SUVmax and SUVmean for bony metastases and degenerative changes Results The PET/CT images were acquired at 30 to 169 minutes (mean [SD], 76.5 [22.8]) after injection of 3.9 to 13.6 mCi (mean [SD], 7.3 [2.4]) of 18F-NaF. The range and mean (SD) of SUVmax for 18F-NaF–avid metastasis were 4.5 to 103.3 and 25.9 (16.6) and for 18F-NaF–avid degenerative changes were 3.3 to 52.1 and 16.5 (7.9), respectively. Conclusions Various skeletal sites have different normal SUVs. Skeletal metastases have different SUVs when compared with benign findings such as degenerative changes.

Detection of osseous metastasis by 18F-NaF/18F-FDG PET/CT versus CT alone.

Purpose Sodium fluoride PET (18F-NaF) has recently reemerged as a valuable method for detection of osseous metastasis, with recent work highlighting the potential of coadministered 18F-NaF and 18F-FDG PET/CT in a single combined imaging examination. We further examined the potential of such combined examinations by comparing dual tracer 18F-NaF/18F-FDG PET/CT with CT alone for detection of osseous metastasis. Patients and Methods Seventy-five participants with biopsy-proven malignancy were consecutively enrolled from a single center and underwent combined 18F-NaF/18F-FDG PET/CT and diagnostic CT scans. PET/CT as well as CT only images were reviewed in blinded fashion and compared with the results of clinical, imaging, or histological follow-up as a truth standard. Results Sensitivity of the combined 18F-NaF/18F-FDG PET/CT was higher than that of CT alone (97.4% vs 66.7%). CT and 18F-NaF/18F-FDG PET/CT were concordant in 73% of studies. Of 20 discordant cases, 18F-NaF/18F-FDG PET/CT was correct in 19 (95%). Three cases were interpreted concordantly but incorrectly, and all 3 were false positives. A single case of osseous metastasis was detected by CT alone, but not by 18F-NaF/18F-FDG PET/CT. Conclusions Combined 18F-NaF/18F-FDG PET/CT outperforms CT alone and is highly sensitive and specific for detection of osseous metastases. The concordantly interpreted false-positive cases demonstrate the difficulty of distinguishing degenerative from malignant disease, whereas the single case of metastasis seen on CT but not PET highlights the need for careful review of CT images in multimodality studies.

Semiquantitative Analysis of the Biodistribution of the Combined 18F-NaF and 18F-FDG Administration for PET/CT Imaging

In this study, we evaluated the biodistribution of the 18F−/18F-FDG administration, compared with separate 18F-NaF and 18F-FDG administrations. We also estimated the interaction of 18F-NaF and 18F-FDG in the 18F−/18F-FDG administration by semiquantitative analysis. Methods: We retrospectively analyzed the data of 49 patients (39 men, 10 women; mean age ± SD, 59.3 ± 15.2 y) who underwent separate 18F-FDG PET/CT and 18F-NaF PET/CT scans as well as 18F−/18F-FDG PET/CT sequentially. The most common primary diagnosis was prostate cancer (n = 28), followed by sarcoma (n = 9) and breast cancer (n = 6). The mean standardized uptake values (SUVs) were recorded for 18 organs in all patients, and maximum SUV and mean SUV were recorded for all the identified malignant lesions. We also estimated the 18F−/18F-FDG uptake as the sum of 18F-FDG uptake and adjusted 18F-NaF uptake based on the ratio of 18F-NaF injected dose in 18F−/18F-FDG PET/CT. Lastly, we compared the results to explore the interaction of 18F-FDG and 18F-NaF uptake in the 18F−/18F-FDG scan. Results: The 18F−/18F-FDG uptake in the cerebral cortex, cerebellum, parotid grand, myocardium, and bowel mostly reflected the 18F-FDG uptake, whereas the uptake in the other analyzed structures was influenced by both the 18F-FDG and the 18F-NaF uptake. The 18F−/18F-FDG uptake in extraskeletal lesions showed no significant difference when compared with the uptake from the separate 18F-FDG scan. The 18F−/18F-FDG uptake in skeletal lesions reflected mostly the 18F-NaF uptake. The tumor-to-background ratio of 18F−/18F-FDG in extraskeletal lesions showed no significant difference when compared with that from 18F-FDG alone (P = 0.73). For skeletal lesions, the tumor-to-background ratio of 18F−/18F-FDG was lower than that from 18F-NaF alone (P < 0.001); however, this difference did not result in missed skeletal lesions on the 18F−/18F-FDG scan. Conclusion: The understanding of the biodistribution of radiopharmaceuticals and the lesion uptake of the 18F−/18F-FDG scan as well as the variations compared with the uptake on the separate 18F-FDG PET/CT and 18F-NaF PET/CT are valuable for more in-depth evaluation of the combined scanning technique.

Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies

Purpose (S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid (18F-FSPG) is a novel radiopharmaceutical for Positron Emission Tomography (PET) imaging. It is a glutamate analogue that can be used to measure xC- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies. Experimental Design For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET. For the human study, five subjects with either primary or metastatic brain cancer were recruited (mean age 50.4 years). After injection of 300 MBq of 18F-FSPG, 3 whole-body PET/Computed Tomography (CT) scans were obtained and safety parameters were measured. The three subjects with brain metastases also had an 18F-FDG PET/CT scan. Quantitative and qualitative comparison of the scans was performed to assess kinetics, biodistribution, and relative efficacy of the tracers. Results In the small animals, the orthotopic brain tumors were visualized well with 18F-FSPG. The high tumor uptake of 18F-FSPG in the GS9L model and the absence of background signal led to good tumor visualization with high contrast (tumor/brain ratio: 32.7). 18F-FDG and 18F-FET showed T/B ratios of 1.7 and 2.8, respectively. In the human pilot study, 18F-FSPG was well tolerated and there was similar distribution in all patients. All malignant lesions were positive with 18F-FSPG except for one low-grade primary brain tumor. In the 18F-FSPG-PET-positive tumors a similar T/B ratio was observed as in the animal model. Conclusions 18F-FSPG is a novel PET radiopharmaceutical that demonstrates good uptake in both small animal and human studies of intracranial malignancies. Future studies on larger numbers of subjects and a wider array of brain tumors are planned. Trial Registration ClinicalTrials.gov NCT01186601