In Vivo SPECT Quantification of Transplanted Cell Survival After Engraftment Using 111In-Tropolone in Infarcted Canine Myocardium
Kimberley J. Blackwood1,2,
Benoit Lewden1,
R. Glenn Wells3,
Jane Sykes1,
Robert Z. Stodilka1,2,
Gerald Wisenberg1,4 and
Frank S. Prato1,2
1 Imaging Program, Lawson Health Research Institute, London, Ontario, Canada; 2 Medical Imaging and Medical Biophysics Department, University of Western Ontario, London, Ontario, Canada; 3 Cardiac Imaging, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; and 4 Division of Cardiology, London Health Sciences Centre, London, Ontario, Canada
View larger version (16K):
[in this window]
[in a new window]
|
FIGURE 1. SPECT VOI (RLm(t)) containing radiolabel released from dead cells (RLd(t)), leaked from viable cells (RLl(t)) (C is fractional loss from viable cells), and in viable cells (SF(t)). DIRF describes kinetics of 111In after cell death.
|
|
View larger version (9K):
[in this window]
[in a new window]
|
FIGURE 2. Nonspecific uptake of 111In in H9c2 cardiomyoblasts. (A) After incubation of 111In-labeled BMSC cellular debris with H9c2 cells, compared with control H9c2 cells labeled with 111In-tropolone, no significant uptake of 111In in H9c2 cells was found (P < 0.001). (B) Evaluation of nonspecific uptake of 111In leaked from viable BMSCs indicated that significant amount of 111In remained within incubating supernatant, compared with H9c2 cells (P < 0.01).
|
|
View larger version (28K):
[in this window]
[in a new window]
|
FIGURE 3. (A) Biexponential fits to time–activity curves (symbols represent normalized raw data) after injection of 111In-labeled cellular debris into canine myocardium (normal, reperfused, and nonreperfused; n = 11). (B) DIRF as calculated from long component of biexponential fits ( = 19.4 ± 4.1 h). (C) Whole-body scans from 1 dog injected with 111In-labeled cellular debris in peri-infarct region of infarcted myocardium. All images are scaled to maximal pixel count and qualitatively demonstrate biodistribution of labeled debris within injected heart (H), liver (L), kidneys (K), and bladder (Bl).
|
|
View larger version (15K):
[in this window]
[in a new window]
|
FIGURE 4. (A) Biexponential fits to SPECT time–activity curves after injection of 111In-tropolone into normal canine myocardium ( = 882.7 ± 242.8 h) (symbols represent normalized raw data). Dogs were serially imaged on injection day (see inset) and weekly thereafter. (B) Whole-body scans from 1 dog injected with 111In-tropolone showing radiolabel in heart on days 0 (d0), 7 (d7), and 15 (d15). All images are scaled to maximal pixel value. (C) SPECT/CT image of 111In radiolabel in normal myocardium of 1 dog localizing 111In injection within heart in transaxial and sagittal planes, respectively. L = liver; K = kidneys.
|
|
View larger version (18K):
[in this window]
[in a new window]
|
FIGURE 5. (A) SPECT time–activity curves showing long component of monoexponential fits for BMSC injections (Tl1/2 = 74.3 ± 7.6 h) (symbols represent normalized raw data). (B) Whole-body scans from 1 dog injected with 111In-labeled BMSCs within infarcted myocardium. Both images are scaled to maximal pixel count and show 111In activity remaining in heart (H) and liver (L) at days 3 (d3) and 7 (d7) after injection. (C) SPECT/CT images confirm presence of BMSCs in myocardium on transplantation day.
|
|
View larger version (8K):
[in this window]
[in a new window]
|
FIGURE 6. Plot of Tm vs. TSF shows calculated half-life of surviving fraction of TCs after corrections for radiolabel leakage (RLl(t)) and death (RLd(t)) kinetics are made to apparent half-life measured by SPECT (RLm(t)). Error bars represent SD, and  represents incorporation of another DIRF curve in estimation of TSF.
|
|
Copyright © 2009 by the Society of Nuclear Medicine.
