Brad Kemp

Dynamic Tracking During Intracoronary Injection of 18F-FDG-Labeled Progenitor Cell Therapy for Acute Myocardial Infarction

We assessed the feasibility of dynamic 3-dimensional (3D) PET/CT tracking of 18F-FDG-labeled circulating progenitor cell (CPC) therapy during intracoronary injection, using a porcine model of acute myocardial infarction (MI). Methods: Human and porcine CPC were radiolabeled with 18F-FDG, with variation in temperature and incubation time to determine optimal conditions. For in vivo experiments, CPC were harvested before induction of infarction (using 90-min coronary balloon occlusion). At 48 h, animals underwent cardiac MRI to assess infarct size. A balloon catheter was placed in the infarct artery at the same location as that used for induction of MI, and during dynamic 3D PET/CT 3 × 107 autologous 18F-FDG progenitor cells were injected through the central lumen using either (a) 3 cycles of balloon occlusion and reperfusion or (b) high-concentration, single-bolus injection without balloon occlusion (n = 3 for both protocols). Peripheral blood was drawn at 1-min intervals during cell injection. Results: Labeling efficiency was optimized by 30-min incubation at 37°C (human CPC, 89.9% ± 4.8%; porcine CPC, 91.6% ± 6.4%). Cell-bound activity showed a nonsignificant decrease at 1 h (human, 74.3% ± 10.7%; porcine, 77.7% ± 12.8%; P > 0.05) and a significant decrease at 2 h (human, 62.1% ± 8.9%; porcine, 68.6% ± 5.4%; P = 0.009). Mean infarct size was similar for both injection protocols (16.3% ± 3.4% and 20.6% ± 2.7%; P > 0.05). Dynamic scanning demonstrated a sharp rise in myocardial activity during each cycle of balloon-occlusion cell delivery, with a significant fall in activity (around 80%) immediately after balloon deflation. The latter was associated with a transient spike in peripheral blood 18F-FDG activity, consistent with the first pass of labeled cells in the systemic circulation. A single spike and gradual fall in myocardial activity was observed with high-concentration, single-bolus therapy. At 1 h, myocardial activity was 8.7% ± 1.5% of total injected dose for balloon-occlusion delivery and 17.8% ± 7.9% for high-concentration, single-bolus delivery (P = 0.08). Conclusion: Dynamic tracking during intracoronary injection of 18F-FDG-labeled CPC is feasible and demonstrates significant cell washout from the myocardium immediately after balloon deflation. High-concentration, single-bolus therapy may be as effective as balloon-occlusion delivery. This tracking technique should facilitate development of improved delivery strategies for cardiac cell therapy.

Biopsy validation of 18F-DOPA PET and biodistribution in gliomas for neurosurgical planning and radiotherapy target delineation: results of a prospective pilot study

BACKGROUND Delineation of glioma extent for surgical or radiotherapy planning is routinely based on MRI. There is increasing awareness that contrast enhancement on T1-weighted images (T1-CE) may not reflect the entire extent of disease. The amino acid tracer (18)F-DOPA (3,4-dihydroxy-6-[18F] fluoro-l-phenylalanine) has a high tumor-to-background signal and high sensitivity for glioma imaging. This study compares (18)F-DOPA PET against conventional MRI for neurosurgical biopsy targeting, resection planning, and radiotherapy target volume delineation. METHODS Conventional MR and (18)F-DOPA PET/CT images were acquired in 10 patients with suspected malignant brain tumors. One to 3 biopsy locations per patient were chosen in regions of concordant and discordant (18)F-DOPA uptake and MR contrast enhancement. Histopathology was reviewed on 23 biopsies. (18)F-DOPA PET was quantified using standardized uptake values (SUV) and tumor-to-normal hemispheric tissue (T/N) ratios. RESULTS Pathologic review confirmed glioma in 22 of 23 biopsy specimens. Thirteen of 16 high-grade biopsy specimens were obtained from regions of elevated (18)F-DOPA uptake, while T1-CE was present in only 6 of those 16 samples. Optimal (18)F-DOPA PET thresholds corresponding to high-grade disease based on histopathology were calculated as T/N > 2.0. In every patient, (18)F-DOPA uptake regions with T/N > 2.0 extended beyond T1-CE up to a maximum of 3.5 cm. SUV was found to correlate with grade and cellularity. CONCLUSIONS (18)F-DOPA PET SUV(max) may more accurately identify regions of higher-grade/higher-density disease in patients with astrocytomas and will have utility in guiding stereotactic biopsy selection. Using SUV-based thresholds to define high-grade portions of disease may be valuable in delineating radiotherapy boost volumes.

The relative contributions of scatter and attenuation corrections toward improved brain SPECT quantification.

Mounting evidence indicates that scatter and attenuation are major confounds to objective diagnosis of brain disease by quantitative SPECT. There is considerable debate, however, as to the relative importance of scatter correction (SC) and attenuation correction (AC), and how they should be implemented. The efficacy of SC and AC for 99mTc brain SPECT was evaluated using a two-compartment fully tissue-equivalent anthropomorphic head phantom. Four correction schemes were implemented: uniform broad-beam AC, non-uniform broad-beam AC, uniform SC + AC, and non-uniform SC + AC. SC was based on non-stationary deconvolution scatter subtraction, modified to incorporate a priori knowledge of either the head contour (uniform SC) or transmission map (non-uniform SC). The quantitative accuracy of the correction schemes was evaluated in terms of contrast recovery, relative quantification (cortical:cerebellar activity), uniformity ((coefficient of variation of 230 macro-voxels) x 100%), and bias (relative to a calibration scan). Our results were: uniform broad-beam (mu = 0.12 cm(-1)) AC (the most popular correction): 71% contrast recovery, 112% relative quantification, 7.0% uniformity, +23% bias. Non-uniform broad-beam (soft tissue mu = 0.12 cm(-1)) AC: 73%, 114%, 6.0%, +21%, respectively. Uniform SC + AC: 90%, 99%, 4.9%, +12%, respectively. Non-uniform SC + AC: 93%, 101%, 4.0%, +10%, respectively. SC and AC achieved the best quantification; however, non-uniform corrections produce only small improvements over their uniform counterparts. SC + AC was found to be superior to AC; this advantage is distinct and consistent across all four quantification indices.

The geometric modulation transfer function of a transmission imaging system that uses a SPECT scintillation camera and parallel hole collimation.

An analytic expression has been derived to calculate the geometric modulation transfer function of a transmission imaging system that uses parallel hole collimation for both the source and the SPECT camera. This expression describes the resolution of the transmission imaging system and replaces the need to use computer intensive Monte Carlo simulations for the system design. The geometric modulation transfer function, denoted as MTFg(rho) = [A2sc(Ssc rho)**A2cc(Scc rho)]D(rho), where ** denotes two-dimensional convolution; Asc(rho) and Acc(rho) are the Fourier transforms (FT) of the aperture functions for the parallel hole source collimator (SC) and the camera collimator (CC) holes, respectively; D(rho) is the FT of the camera response; and ssc and scc are scaling constants that depend on the respective collimator dimensions, the system dimensions, the object distance above camera collimator and whether MTFg(rho) is calculated for the object or image plane. The theoretical MTFg(rho) was verified with Monte Carlo simulations and experimental results. The formalism shows that the system resolution is characterized by the camera resolution and a combination of the resolutions of the source and camera collimators. This expression can be used to optimize the design of transmission imaging systems to be used in nuclear medicine.

WE‐G‐214‐02: Utility of 18F‐FDOPA PET for Radiotherapy Target Delineation in Glioma Patients

Purpose: To evaluate the impact of adding 18F‐FDOPA‐PET, an amino acid tracer, to standard of care MRI for radiotherapy target volume delineation for gliomas. Methods: 6 patients with newly diagnosed braintumors were given 5.0 mCi +/− 10% of 3,4‐dihydroxy‐6‐[18F]‐fluoro‐L‐phenylalanine (18F‐FDOPA), and underwent a 10‐minute PET/CT acquisition. Overall pathology confirmed WHO grade 3 astrocytoma (n=3), grade 3 oligoastrocytoma (n=1), and glioblastoma (n=2). T1‐weighted post gadolinium (T1‐gad) and T2‐weighted/FLAIR MRI sequences were rigidly aligned to the 18F‐FDOPA‐PET/CT. Three experienced radiation oncologists contoured the T2/FLAIR abnormality, T1‐gad enhancement, and areas of 18F‐FDOPA uptake separately. An experienced nuclear medicine physician contoured 18F‐FDOPA uptake, which was considered as the gold standard for positive disease on PET imaging. Intersection, union, and exclusion boolean operators were performed to determine discordance and concordance between MRI and 18F‐FDOPA‐PET, along with interobserver variability defining 18F‐FDOPA‐PET volume. In addition, uniform expansions of the T1‐gad contours were performed in increments of 0.5 cm until 100% of the 18F‐FDOPA‐PET volume was covered. Results: 18F‐FDOPA‐PET uptake was observed in all patients, with interobserver delineation variability between radiation oncologists (RadOnc1‐RadOnc3) and the gold standard ranging from 47% less to 191% more volume. On average 9.5% (0.3%–29.1%) of the 18F‐FDOPA‐PET gold standard volume extended beyond the RadOnc T2/FLAIR volumes. Half of the cases had no enhancement, and of the remainder on average 77.8% (61.3%–93.1%) of the 18F‐FDOPA‐PET volume extended outside the T1‐gad enhancement. An average expansion of 2.0cm (1.0cm–5.0cm) beyond the T1‐gad contours was necessary to cover 100% of the 18F‐FDOPA‐PET volume. Conclusions: This work introduces the potential utilization of 18F‐FDOPA‐PET for identifying positive disease not visible with conventional MRI and the potential to customize radiotherapy target volumes to the active disease. Future studies will correlate pathology with concordant and discordant regions, and compare biopsy confirmed results with automatic segmentation techniques for 18F‐FDOPA‐PET. Funding has been provided by Brains Together for a Cure