Mehran Jamali

Pilot Comparison of ⁶⁸Ga-RM2 PET and ⁶⁸Ga-PSMA-11 PET in Patients with Biochemically Recurrent Prostate Cancer.

Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)] (68Ga-PSMA-11) is a PET tracer that can detect prostate cancer relapses and metastases by binding to the extracellular domain of PSMA. 68Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (68Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptors. We present pilot data on the biodistribution of these PET tracers in a small cohort of patients with biochemically recurrent prostate cancer. Methods: Seven men (mean age ± SD, 74.3 ± 5.9 y) with biochemically recurrent prostate cancer underwent both 68Ga-PSMA-11 PET/CT and 68Ga-RM2 PET/MRI scans. SUVmax and SUVmean were recorded for normal tissues and areas of uptake outside the expected physiologic biodistribution. Results: All patients had a rising level of prostate-specific antigen (mean ± SD, 13.5 ± 11.5) and noncontributory results on conventional imaging. 68Ga-PSMA-11 had the highest physiologic uptake in the salivary glands and small bowel, with hepatobiliary and renal clearance noted, whereas 68Ga-RM2 had the highest physiologic uptake in the pancreas, with renal clearance noted. Uptake outside the expected physiologic biodistribution did not significantly differ between 68Ga-PSMA-11 and 68Ga-RM2; however, 68Ga-PSMA-11 localized in a lymph node and seminal vesicle in a patient with no abnormal 68Ga-RM2 uptake. Abdominal periaortic lymph nodes were more easily visualized by 68Ga-RM2 in two patients because of lack of interference by radioactivity in the small intestine. Conclusion: 68Ga-PSMA-11 and 68Ga-RM2 had distinct biodistributions in this small cohort of patients with biochemically recurrent prostate cancer. Additional work is needed to understand the expression of PSMA and gastrin-releasing peptide receptors in different types of prostate cancer.

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.

Simultaneous whole-body time-of-flight 18F-FDG PET/MRI: a pilot study comparing SUVmax with PET/CT and assessment of MR image quality.

Purpose The recent introduction of hybrid PET/MRI scanners in clinical practice has shown promising initial results for several clinical scenarios. However, the first generation of combined PET/MRI lacks time-of-flight (TOF) technology. Here we report the results of the first patients to be scanned on a completely novel fully integrated PET/MRI scanner with TOF. Materials and Methods We analyzed data from patients who underwent a clinically indicated 18F FDG PET/CT, followed by PET/MRI. Maximum standardized uptake values (SUVmax) were measured from 18F FDG PET/MRI and 18F FDG PET/CT for lesions, cerebellum, salivary glands, lungs, aortic arch, liver, spleen, skeletal muscle, and fat. Two experienced radiologists independently reviewed the MR data for image quality. Results Thirty-six patients (19 men, 17 women, mean [±standard deviation] age of 61 ± 14 years [range: 27–86 years]) with a total of 69 discrete lesions met the inclusion criteria. PET/CT images were acquired at a mean (±standard deviation) of 74 ± 14 minutes (range: 49–100 minutes) after injection of 10 ± 1 mCi (range: 8–12 mCi) of 18F FDG. PET/MRI scans started at 161 ± 29 minutes (range: 117 – 286 minutes) after the 18F FDG injection. All lesions identified on PET from PET/CT were also seen on PET from PET/MRI. The mean SUVmax values were higher from PET/MRI than PET/CT for all lesions. No degradation of MR image quality was observed. Conclusion The data obtained so far using this investigational PET/MR system have shown that the TOF PET system is capable of excellent performance during simultaneous PET/MR with routine pulse sequences. MR imaging was not compromised. Comparison of the PET images from PET/CT and PET/MRI show no loss of image quality for the latter. These results support further investigation of this novel fully integrated TOF PET/MRI instrument.

Circulating Tumor Microemboli Diagnostics for Patients with Non–Small-Cell Lung Cancer

Introduction: Circulating tumor microemboli (CTM) are potentially important cancer biomarkers, but using them for cancer detection in early-stage disease has been assay limited. We examined CTM test performance using a sensitive detection platform to identify stage I non–small-cell lung cancer (NSCLC) patients undergoing imaging evaluation. Methods: First, we prospectively enrolled patients during 18F-FDG PET-CT imaging evaluation for lung cancer that underwent routine phlebotomy where CTM and circulating tumor cells (CTCs) were identified in blood using nuclear (DAPI), cytokeratin (CK), and CD45 immune-fluorescent antibodies followed by morphologic identification. Second, CTM and CTC data were integrated with patient (age, gender, smoking, and cancer history) and imaging (tumor diameter, location in lung, and maximum standard uptake value [SUVmax]) data to develop and test multiple logistic regression models using a case-control design in a training and test cohort followed by cross-validation in the entire group. Results: We examined 104 patients with NSCLC, and the subgroup of 80 with stage I disease, and compared them to 25 patients with benign disease. Clinical and imaging data alone were moderately discriminating for all comers (Area under the Curve [AUC] = 0.77) and by stage I disease only (AUC = 0.77). However, the presence of CTM combined with clinical and imaging data was significantly discriminating for diagnostic accuracy in all NSCLC patients (AUC = 0.88, p value = 0.001) and for stage I patients alone (AUC = 0.87, p value = 0.002). Conclusion: CTM may add utility for lung cancer diagnosis during imaging evaluation using a sensitive detection platform.

Molecular profiling of single circulating tumor cells from lung cancer patients

Significance There exists an urgent need for minimally invasive molecular analysis tools for cancer assessment and management, particularly in advanced-stage lung cancer, when tissue procurement is challenging and gene mutation profiling is crucial to identify molecularly targeted agents for treatment. High-throughput compartmentalization and multigene profiling of individual circulating tumor cells (CTCs) from whole-blood samples using modular gene panels may facilitate highly sensitive, yet minimally invasive characterization of lung cancer for therapy prediction and monitoring. We envision this nanoplatform as a compelling research tool to investigate the dynamics of cancer disease processes, as well as a viable clinical platform for minimally invasive yet comprehensive cancer assessment. Circulating tumor cells (CTCs) are established cancer biomarkers for the “liquid biopsy” of tumors. Molecular analysis of single CTCs, which recapitulate primary and metastatic tumor biology, remains challenging because current platforms have limited throughput, are expensive, and are not easily translatable to the clinic. Here, we report a massively parallel, multigene-profiling nanoplatform to compartmentalize and analyze hundreds of single CTCs. After high-efficiency magnetic collection of CTC from blood, a single-cell nanowell array performs CTC mutation profiling using modular gene panels. Using this approach, we demonstrated multigene expression profiling of individual CTCs from non–small-cell lung cancer (NSCLC) patients with remarkable sensitivity. Thus, we report a high-throughput, multiplexed strategy for single-cell mutation profiling of individual lung cancer CTCs toward minimally invasive cancer therapy prediction and disease monitoring.

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.

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.

Initial Experience With Simultaneous 18F-FDG PET/MRI in the Evaluation of Cardiac Sarcoidosis and Myocarditis

Purpose The purpose of this study was to compare combined PET/MRI with PET/CT and cardiac MRI in the evaluation of cardiac sarcoidosis and myocarditis. Methods Ten patients (4 men and 6 women; 56.1 ± 9.6 years old) were prospectively enrolled for evaluation of suspected cardiac sarcoidosis or myocarditis. Written informed consent was obtained. Following administration of 9.9 ± 0.9 mCi 18F-FDG, patients underwent standard cardiac PET/CT followed by combined PET/MRI using a simultaneous 3-T scanner. Cardiac MRI sequences included ECG-triggered cine SSFP, T2-weighted, and late gadolinium-enhanced imaging. Myocardial involvement was assessed with separate analysis of combined PET/MRI, PET/CT, and cardiac MRI data using dedicated postprocessing software. Estimates of radiation dose were derived from the applied doses of 18F-FDG and CT protocol parameters. Results Imaging was acquired with a delay from 18F-FDG injection of 90.2 ± 27.4 minutes for PET/CT and 207.7 ± 40.3 minutes for PET/MRI. Total scan time for PET/MRI was significantly longer than for PET/CT (81.4 ± 14.8 vs 12.0 minutes, P < 0.001). Total effective radiation dose was significantly lower for PET/MRI compared with PET/CT (6.9 ± 0.6 vs 8.2 ± 1.1 mSv, P = 0.007). There was no significant difference in the number of positive cases identified between combined PET/MRI (n = 10 [100%]), PET/CT (n = 6 [60%]), and cardiac MRI (n = 8 [80%]), P = 0.091. Conclusions Simultaneous cardiac PET/MRI is feasible in the evaluation of cardiac sarcoidosis and myocarditis achieving diagnostic image quality.

The potential of TOF PET-MRI for reducing artifacts in PET images

Here we evaluated the potential of TOF PET/MRI to reduce various PET image artifacts, by comparing the images to non-TOF PET/MRI, TOF PET/CT and non-TOF PET/CT.

A Prospective, Matched Comparison Study of SUV Measurements From Time-of-Flight Versus Non-Time-of-Flight PET/CT Scanners.

Purpose As quantitative 18F-FDG PET numbers and pooling of results from different PET/CT scanners become more influential in the management of patients, it becomes imperative that we fully interrogate differences between scanners to fully understand the degree of scanner bias on the statistical power of studies. Patients and Methods Participants with body mass index (BMI) greater than 25, scheduled on a time-of-flight (TOF)–capable PET/CT scanner, had a consecutive scan on a non–TOF-capable PET/CT scanner and vice versa. SUVmean in various tissues and SUVmax of malignant lesions were measured from both scans, matched to each subject. Data were analyzed using a mixed-effects model, and statistical significance was determined using equivalence testing, with P < 0.05 being significant. Results Equivalence was established in all baseline organs, except the cerebellum, matched per patient between scanner types. Mixed-effects method analysis of lesions, repeated between scan types and matched per patient, demonstrated good concordance between scanner types. Conclusions Patients could be scanned on either a TOF or non–TOF-capable PET/CT scanner without clinical compromise to quantitative SUV measurements.