Dynamic Planar Research Articles

Use of a Novel Receptor-Targeted (CD206) Radiotracer,99mTc-Tilmanocept, and SPECT/CT for Sentinel Lymph Node Detection in Oral Cavity Squamous Cell Carcinoma

Sentinel lymph node biopsy has been proposed as an alternative to up-front elective neck dissection (END) for determination of pathologic nodal status in patients undergoing surgical treatment for oral cavity squamous cell carcinoma (OSCC) with clinically negative neck (cN0). Sentinel lymph node biopsy using current standard tracer agents and imaging adjuncts such as radiolabeled sulfur-colloid and planar lymphoscintigraphy (LS), however, is associated with several drawbacks. To assess the preliminary utility of technetium Tc 99m (99mTc)-tilmanocept, a novel molecular imaging agent for sentinel lymph node (SLN) mapping, in OSCC. Prospective, nonrandomized, single-arm, part of an ongoing phase 3 clinical trial. Patients had previously untreated, clinically and radiographically node-negative OSCC (T1-4aN0M0) at an academic tertiary referral center. Patients received a single dose of 50 µg 99mTc-tilmanocept injected peritumorally followed by dynamic planar LS and fused single-photon emission computed tomography/computed tomography (SPECT/CT) prior to surgery. Surgical intervention consisted of excision of the primary tumor and radioguided SLN dissection followed by planned END. The excised lymph nodes (SLNs and non-SLNs) underwent histopathologic evaluation for presence of metastatic disease. False-negative rate and negative predictive value of SLNB using 99mTc-tilmanocept and comparison of planar LS with SPECT/CT in SLN localization. Twelve of 20 patients (60%) had metastatic neck disease on pathologic examination. All 12 had at least 1 SLN positive for metastases. No patients had a positive END node who did not have at least 1 positive SLN. These data yield a false-negative rate of 0% and negative predictive value of 100% using 99mTc-tilmanocept in this setting. Dynamic planar LS and SPECT/CT revealed a mean (range) number of hot spots per patient of 2.9 (1-7) and 3.7 (1-12), respectively. Compared with planar LS, SPECT/CT identified additional putative SLNs in 11 of 20 cases (55%). The high negative predictive value and low false-negative rate in identification of occult metastases shows 99mTc-tilmanocept to be a promising agent in SLN identification in patients with OSCC. Use of SPECT/CT improves preoperative SLN localization including delineation of SLN locations near the primary tumor when compared with planar LS imaging. clinicaltrials.gov Identifier: NCT00911326.

Assessment of renal function in mice with unilateral ureteral obstruction using 99mTc-MAG3 dynamic scintigraphy

BackgroundRenal scintigraphy using 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) is widely used for the assessment of renal function in humans. However, the application of this method to animal models of renal disease is currently limited, especially in rodents. Here, we have applied 99mTc-MAG3 renal scintigraphy to a mouse model of unilateral ureteral obstruction (UUO) and evaluated its utility in studying obstructive renal disease.MethodsUUO mice were generated by complete ligation of the left ureter. Sham-operated mice were used as a control. Renal function was investigated on days 0, 1, 3, and 6 post-surgery using dynamic planar imaging of 99mTc-MAG3 activity following retro-orbital injection. Time-activity curves (TACs) were produced for individual kidneys and renal function was assessed by 1) the slope of initial 99mTc-MAG3 uptake (SIU), which is related to renal perfusion; 2) peak activity; and 3) the time-to-peak (TTP). The parameters of tubular excretion were not evaluated in this study as 99mTc-MAG3 is not excreted from UUO kidneys.ResultsCompared to sham-operated mice, SIU was remarkably (>60%) reduced in UUO kidneys at day 1 post surgery and the TACs plateaued, indicating that 99mTc-MAG3 is not excreted in these kidneys. The plateau activity in UUO kidneys was relatively low (~40% of sham kidney’s peak activity) as early as day1 post surgery, demonstrating that uptake of 99mTc-MAG3 is rapidly reduced in UUO kidneys. The time to plateau in UUO kidneys exceeded 200 sec, suggesting that 99mTc-MAG3 is slowly up-taken in these kidneys. These changes advanced as the disease progressed. SIU, peak activity and TTPs were minimally changed in contra-lateral kidneys during the study period.ConclusionsOur data demonstrate that renal uptake of 99mTc-MAG3 is remarkably and rapidly reduced in UUO kidneys, while the changes are minimal in contra-lateral kidneys. The parametric analysis of TACs suggested that renal perfusion as well as tubular uptake is reduced in UUO kidneys. This imaging technique should allow non-invasive assessments of UUO renal injury and enable a more rapid interrogation of novel therapeutic agents and protocols.

Technetium-99m sulfur colloid (TSC) as a phenotypic probe for predicting pharmacokinetics (PK) and palmar-plantar erythrodysesthesia (PPE) toxicity of pegylated liposomal doxorubicin (PLD) in patients (pts) with recurrent epithelial ovarian cancer (EOC).

5050 Background: There is significant variability in the PK and PD (efficacy and toxicity) of PLD. Clearance (CL) of PLD has been proposed to occur primarily via uptake by cells of the mononuclear phagocyte system (MPS) mainly located in the liver, spleen, and blood. TSC is a radioactive colloid used clinically for diagnostic and functional imaging of the MPS. Our aim is to evaluate TSC as a phenotypic probe of MPS activity, which may predict PLD PK and PPE toxicity in pts (n=9) with EOC. Methods: Prior to administration of PLD on cycle 1 day 1 (C1D1), TSC was administered at 10 mCi IVP × 1. Dynamic planar and SPECT/CT images of the liver, spleen and hands were acquired using a gamma camera. Blood samples were collected up to 60 min after TSC and analyzed for radioactivity using a gamma counter. On C1D1, PLD was administered at 40 mg/m2 alone or at 30 mg/m2 in combination with carboplatin IV over 1 to 3 h. Serial PK samples were obtained from 0h to 672h post PLD dose. Plasma was processed to measure encapsulated and released doxorubicin (dox) using solid phase separation and HPLC. CL of PLD and TSC were calculated by non-compartmental analysis. The grade of PPE toxicity was determined by NCI CTCAE (v4.03) criteria. Results: Nine patients have undergone TSC imaging and eight patients completed TSC blood PK and PLD plasma PK studies. There was a positive linear relationship between TSC CL and encapsulated dox CL (R2 = 0.61, p=0.02). When patients were subdivided, there was a stronger relationship between TSC CL and encapsulated dox CL (R2 = 0.81, p=0.03) in pts receiving PLD monotherapy. A positive relationship using Spearman’s correlation (ρ=0.84, p=0.006) was also found between maximum grade PPE toxicity developed and estimated AUC of encapsulated dox in hands [(TSC AUCBlood)/(TSC AUCHand)*Encapsulated Dox AUCPlasma]. Conclusions: These results suggest that TSC is a probe for MPS function and PLD PK and PD and may be used to individualize PLD therapy in pts with EOC. In addition, our findings suggest TSC may be able to predict the development of PPE in patients.

Renogram comparison of p-[18F]fluorohippurate with o-[125I]iodohippurate and [99mTc]MAG3 in normal rats

We recently identified p-[(18)F]fluorohippurate ([(18)F]PFH) as a potential positron emission tomography (PET) renal agent. The objective of this study was to compare renogram parameters of [(18)F]PFH with o-[(125)I]iodohippurate ([(125)I]OIH) as a surrogate for the renal imaging gold standard (131)I-OIH and with a clinically used agent [(99m)Tc]MAG3. Normal Sprague-Dawley rats (n=4) were sequentially imaged on days 1, 2, and 3 using [(99m)Tc]MAG3 (18.1-19.1 MBq, dynamic planar), [(18)F]PFH (2.6-4.1 MBq, dynamic PET), and [(125)I]OIH (7.7-13.5 MBq, dynamic planar), respectively. The PET data were binned into frames of 30 s each, whereas the planar images were acquired as 30 s per frame. Regions of interest were drawn on both kidneys, and decay-corrected renograms were generated for each imaging modality. The PET-derived [(18)F]PFH renograms revealed an average time-to-peak (T(max)) of 4.8±2.4 min, which was comparable to the T(max) of 3.6±1.7 min and 4.3±1.7 min for [(125)I]OIH and [(99m)Tc]MAG3 renograms, respectively. The average time-to-half-maximal activity was found to be 16.6±6.6 min, 8.3±2.4 min, and more than 20 min with [(18)F]PFH, [(125)I]OIH, and [(99m)Tc]MAG3, respectively. Compared with [(99m)Tc]MAG3, the renogram parameters of [(18)F]PFH seem to be closer to those obtained from [(125)I]OIH. The quality of the renogram and the images obtained with the dynamic [(18)F]PFH PET study were remarkably better than those obtained with the [(99m)Tc]MAG3 dynamic planar imaging study.

Patient-Specific Radiation Dosimetry of 99mTc-HYNIC-Tyr3-Octreotide in Neuroendocrine Tumors

(99m)Tc-hydrazinonicotinamide-Tyr(3)-octreotide ((99m)Tc-HYNIC-TOC) is increasingly gaining acceptance as a new radiopharmaceutical for the diagnosis of pathologic lesions overexpressing somatostatin receptors. However, little information has been published about the radiation dosimetry of this agent. The aim of this study was to assess the biodistribution and radiation dosimetry of commercially available (99m)Tc-HYNIC-TOC. A dose calculation procedure designed to be feasible to implement in a busy clinical environment was used. Twenty-eight patients were imaged for suspected neuroendocrine tumors using a series of whole-body planar, dynamic planar, and SPECT/CT studies, after injection with (99m)Tc-HYNIC-TOC. Patient-specific dosimetry was performed using the OLINDA/EXM software with time-integrated activity coefficients estimated from a hybrid planar/SPECT technique. A phantom experiment was performed to establish adaptive thresholds for determination of source region volumes and activities. Pathologic uptake, diagnosed as due to neuroendocrine tumors, was observed in 12 patients. Normal organs with significant uptake included the kidneys, liver, and spleen. The mean effective dose after (99m)Tc-HYNIC-TOC injection was 4.6 ± 1.1 mSv. Average normal-organ doses were 0.030 ± 0.012, 0.021 ± 0.007, and 0.012 ± 0.005 mGy/MBq for the spleen, kidneys, and liver, respectively. The interpatient kidney dose ranged from 0.011 to 0.039 mGy/MBq, whereas the range of tumor doses varied from 0.003 to 0.053 mGy/MBq. The ratio of tumor to kidney dose ranged from 0.13 to 2.9. The optimal thresholds for recovery of true activity in the phantom study were significantly lower than those used for volume determination. The patient-specific 3-dimensional dosimetry protocol used in this study is a clinically feasible technique that has been applied to demonstrate large dose variations in tumors and normal organs between patients imaged with (99m)Tc-HYNIC-TOC.

Technetium-99m sulfur colloid (TSC) as a phenotypic probe for the pharmacokinetics (PK) and pharmacodynamics (PD) of pegylated liposomal doxorubicin (PLD) in patients (pts) with recurrent epithelial ovarian cancer (EOC).

2582 Background: There is significant inter- and intra-patient variability in the PK and PD (efficacy and toxicity) of PLD in pts with EOC and other malignancies. This has been attributed to age and gender, but more specifically, may be related to the mononuclear phagocyte system (MPS). Clearance (CL) of PLD has been proposed to occur primarily via uptake by monocytes, dendritic cells, and macrophages mainly located in the liver, spleen, and blood. TSC is a radioactive colloid used clinically for diagnostic and functional imaging of the MPS. Our aim is to evaluate TSC as a phenotypic probe of MPS activity, which may predict PLD PK and PD in pts with EOC. Methods: Prior to (day -7 to -1) administration of PLD on cycle 1 day 1 (C1D1), TSC was administered at 10 mCi IV × 1. Dynamic planar and SPECT/CT images of the liver and spleen were acquired using a gamma camera. Blood samples were collected up to 60 min after TSC and analyzed for radioactivity using a gamma counter. On C1D1, PLD was administered at 40 mg/m2 alone or at 30 mg/m2 in combination with carboplatin IV over 1 to 1.5 h. Serial blood samples were collected up to 28 days after PLD. Plasma samples were processed to measure encapsulated (encap) and released doxorubicin via HPLC with fluorescence. Results: Six pts have undergone TSC imaging and blood PK, and PLD plasma PK studies. Mean ± SD encap doxorubicin CL and TSC CL were 25.4 ± 4.1 mL/h and 18.9 ± 5.4 mL/h, respectively. There was a positive linear relationship between TSC CL and encap doxorubicin CL (R2 = 0.58). Mean ± SD of encap doxorubicin area under the concentration versus time curve (AUC) and TSC splenic outflow were 2.4 ± 0.5 mg/mL·h and 0.5 ± 0.1 s-1, respectively. There was a positive linear relationship between TSC splenic outflow and encap doxorubicin AUC (R2 = 0.85). There was no relationship between TSC AUC in the liver and spleen and PLD PK. Conclusions: These results suggest that TSC is a probe for MPS function and PLD PK and may be used to individualize PLD therapy in pts with EOC and other malignancies. Evaluation of the relationship between TSC and PLD PD is undergoing further investigation.

Rapid hepatic clearance of 99mTc‐TMEOP: a new candidate for myocardial perfusion imaging

(99m)Tc labeled radiotracers used in clinical practice lack the perfect characteristics for myocardial perfusion imaging. In particular, the high liver uptake can interfere in the interpretation of the inferior myocardial wall. Within the tricarbonyl approach, we used tris(pyrazolyl)methane (99m)Tc organometallic complexes as a lead structure. Herein we present the production, in vivo and in vitro metabolic studies in rats and the first in vivo biodistribution in rats for tri-methoxy-tris-pyrazolyl-(99m)Tc-(CO)(3) ((99m)Tc-TMEOP), compared with (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. The chemical identity of (99m)Tc-TMEOP was characterized by RP-HPLC. The octanol-water partition coefficient was determined under physiological conditions. In vitro stability and protein binding were determined using RP-HPLC. In vivo stability was determined in blood, heart, liver and kidney homogenates, intestine and urine using RP-HPLC. In vivo biodistribution was determined using dynamic planar acquisitions. Pinhole gated SPECT images were performed in other animals. Cardiac, liver and lung uptake were expressed as differential uptake ratios by drawing regions of interest in the organs of interest and around the total body. Heart-liver and heart-lung ratios were derived. Cardiac uptake was also expressed as percentage of injected activity. SPECT images were processed to determine the heart-liver ratio on SPECT images, to compare functional parameters between different tracers and to visualize homogeneous intracardiac tracer distribution. (99m)Tc-TMEOP is a moderately lipophilic cation, is stable and does not undergo any transformation in vitro. (99m)Tc-TMEOP also shows a high in vivo stability. In vivo imaging shows liver kinetics faster than those of (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. Cardiac uptake and functional analysis of pinhole gated SPECT data are comparable to those of (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. Although (99m)Tc-TMEOP shows a cardiac uptake between those of (99m)Tc-sestamibi and (99m)Tc-tetrofosmin, a better heart-liver ratio is obtained due to the faster liver washout. These results suggest possible faster cardiac perfusion imaging using (99m)Tc-TMEOP without liver activity interference.

Breast lymphatic drainage via the pulmonary lymphatic system

A 43-year-old woman underwent sentinel lymph node localisation prior to a left mastectomy and sentinel node biopsy for recurrent multifocal left-sided breast cancer. Previous treatment included a wide local excision and left axillary nodal clearance 15 months ago. Following one peri-areolar intradermal injection of 15 MBq of Tcantimony colloid in the upper inner quadrant of the left breast, dynamic planar imaging failed to identify a sentinel node. SPECT/CT imaging demonstrated a lymphatic channel extending from the left subpectoral region through the lingula of the left lung into the mediastinum posterior to the pulmonary trunk and terminating in the subcarinal nodal station (arrow). This unusual pattern of breast lymphatic drainage via the pulmonary lymphatic system is attributed to opening of collateral lymphatic channels following the previous left axillary nodal clearance. A left internal mammary sentinel lymph node (arrowhead) was also demonstrated and confirmed intraoperatively. While it is commonly believed that spread of breast cancer beyond the regional lymph nodes is haematogenous, it is also increasingly being recognised that traditional anatomical descriptions of lymphatic anatomy do not necessarily reflect observed variations in lymphatic pathways [1, 2]. Given that breast cancer is one of the known extrathoracic malignancies that metastasise to mediastinal nodes [3–5], this finding of a direct communication of breast lymphatic drainage with the intrapulmonary lymphatic system provides a potential mechanism for this pattern of spread. This case highlights how the combination of functional and anatomical information provided by SPECT/CT in lymphoscintigraphy continues to improve our understanding of potential paths of cancer spread.

(R,S)-2-Iodo-reboxetine: Development as a novel SPECT radiotracer for imaging the noradrenaline transporter in brain

Introduction: Dysregulation of noradrenergic function has been implicated in multiple brain disorders, including: depression, post-traumatic stress, anxiety, attention-deficit/hyperactivity disorder, Alzheimer's disease and Parkinson's disease. Despite this, few attempts have been made to develop radiotracers for imaging the noradrenaline transporter (NAT) in vivo using either positron emission tomography or single photon emission computerised tomography (SPECT). We set out to develop a novel SPECT radiotracer, based on the selective noradrenaline re-uptake inhibitor, reboxetine, for imaging the NAT in brain. Methods: The lead candidate, (R,S)-2-iodo-reboxetine [1], was radiolabelled via electrophillic iododestannylation of the corresponding tin precursor using peracetic acid as an oxidant. In vitro binding assays, in vitro and ex vivo brain autoradiography, in vivo biodistribution and pharmacokinetics studies using whole body dynamic planar imaging and ex vivo displacement studies, were performed in rats in order to evaluate radiolabelled (R,S)-2-iodo-reboxetine as a NAT SPECT radiotracer. Results: (R,S)-2-Iodo-reboxetine against 3H-Nisoxetine has nanomolar affinity for the NAT in homogenates of whole rat brain (Ki = 8.4 ± 1.7 nM, mean ± SEM, n = 5). 123I and 125I radiolabelling of (R,S)-2-iodo-reboxetine was successfully accomplished. The percentage non specific binding (of total binding), as measured by in vitro autoradiography with 123I-(R,S)-2-iodo-reboxetine in rat brain sections (mean ± SEM, n = 3), was 26 ± 2% in the locus coeruleus, 97 ± 3% in the corpus callosum, 98 ± 2% in the caudate putamen, 97 ± 2% in the hippocampus, 87 ± 6% in the anterior thalamus, 75 ± 2% in the raphe and 85 ± 8% in the cerebral cortex. Ex vivo autoradiography showed a specific to non-specific binding ratio (locus coeruleus:striatum) of 2.7. In vivo brain uptake was 2.96 ± 0.33% (mean ± SEM, n = 4) of the injected dose, as measured by whole body dynamic planar imaging. The elimination route of 123I-(R,S)-2-iodo-reboxetine, determined by both in vivo whole body dynamic planar imaging and ex vivo studies, was mainly intestinal. Conclusion: The data indicate that 123I-(R,S)-2-iodo-reboxetine may have potential as a radiotracer for imaging the NAT in brain.

SU‐GG‐I‐180: Application of Molecular Imaging in the Monitoring of Angiogenesis of a Hindlimb Ischemia Model

Purpose: Avβ3 integrin expression is a characteristic feature of the angiogenic phenotype of endothelial cells. Targeted molecular imaging of integrins may be a further step forward in the evaluation of specific and early aspects of angiogenesis. The purpose of our study was to investigate the potential of molecular imaging with the aid of a dedicated high resolution γ camera in the rabbit hindlimb ischemia model. Method and Materials: A 99mTc labeled cyclic RGD peptide ([c RGDfk‐His]‐99mTc) was employed for angiogenesis imaging in the New Zealand white rabbits hindlimb ischemia model. Imaging of αvβ3 expression was performed in two animal groups. In group A imaging was employed 3 days and in group B 9 days post femoral artery occlusion (2 rabbits in each group). Each rabbit was injected intravenously with 200 μl of [c RGDfk‐His]‐99mTc (0.5 mCi). Consequently dynamic planar imaging was performed with a high resolution gamma camera with FOV 5×10 cm, equipped with a parallel hole collimator. Static 8 minute images at 80 minutes post injection of the radiotracer were acquired. Results: We have imaged 4 rabbits. An increase of 12.2% was observed in group A in relative radiotracer retention at the ischemic hindlimb compared to control. In group B this relative radiotracer retention was increased to 25.8%. The control limbs showed an increase in the radiotracer retention at day 9 but still much lower compared to ischemic limbs. Moreover, radiotracer accumulation was observed to a region distal to the original area of occlusion, where the newly formed proximal collaterals are located. Conclusion: Our study demonstrates that the phenomenon of angiogenesis proceeds and is maximized within on day 9 following induction of ischemia in a mammalian experimental model. Further studies are deemed necessary in order to establish this conclusion and provide quantitative results.

Estimation of 123I-IMP arterial blood activity from dynamic planar imaging of the chest using a graph plot method for the quantification of regional cerebral blood flow

I-123-labeled N-isopropyl-p-iodoamphetamine ((123)I-IMP) is used for the measurement of regional cerebral blood flow (rCBF). A continuous or single arterial blood sampling (ABS) is necessary to estimate an integral of arterial input function (AIF) for the measurement of rCBF by using a microsphere model analysis. Therefore, a method of measuring rCBF without any blood sampling is desired. The aim of this study was to establish a method to estimate the AIF from the time-activity curve of the lungs after an injection of (123)I-IMP, using a regression analysis for the measurement of rCBF without any blood sampling. Thirty-seven prospective studies in 10 consecutive patients were enrolled. A chest planar dynamic imaging for 3 min and continuous ABS for 5 min after a bolus injection of 167MBq (123)I-IMP were performed in all studies. Data from the chest imaging were analyzed in comparison with ABS data (AIF(5)) in the first 10 studies, and an equation for estimation yielding accurate AIF(5) from the total counts cleared from the lungs, during 5 min after injection of (123)I-IMP (TCL(5)), was derived. The validity of the proposed method was evaluated in the subsequent 27 studies. A good correlation was obtained between the AIF and TCL by regression analysis in the first 10 studies (r = 0.94, P < 0.001). An equation for the estimation of AIF by the regression analysis in the first 10 studies was defined as follows: estimated AIF = 2147 + 4.174 x TCL(5). In the subsequent 27 studies, a good linear correlation was obtained between the measured and the estimated AIF(5) by using the equation (r = 0.79, P < 0.001). AIF(5) can be accurately estimated from TCL(5). Therefore, estimated AIF(5) can be used for the measurement of rCBF instead of ABS data.

Dynamic Planar Solid Phase Microextraction−Ion Mobility Spectrometry for Rapid Field Air Sampling and Analysis of Illicit Drugs and Explosives

A preconcentration device that targets the volatile chemical signatures associated with illicit drugs and explosives (high and low) has been designed to fit in the inlet of an ion mobility spectrometer (IMS). This is the first reporting of a fast and sensitive method for dynamic sampling of large volumes of air using planar solid phase microextraction (PSPME) incorporating a high surface area for absorption of analytes onto a sol-gel polydimethylsiloxane (PDMS) coating for direct thermal desorption into an IMS. This device affords high extraction efficiencies due to strong retention properties at ambient temperature, resulting in the detection of analyte concentrations in the parts per trillion range when as low as 3.5 L of air are sampled over the course of 10 s (absolute mass detection of less than a nanogram). Dynamic PSPME was used to sample the headspace over the following: 3,4-methylenedioxymethamphetamine (MDMA) tablets resulting in the detection of 12-40 ng of piperonal, high explosives (Pentolite) resulting in the detection of 0.6 ng of 2,4,6-trinitrotoluene (TNT), and low explosives (several smokeless powders) resulting in the detection of 26-35 ng of 2,4-dinitrotoluene (2,4-DNT) and 11-74 ng of diphenylamine (DPA).

99mTc-Mebrofenin Hepatobiliary Scintigraphy with SPECT for the Assessment of Hepatic Function and Liver Functional Volume Before Partial Hepatectomy

Preoperative evaluation of future remnant liver (FRL) function is crucial in the determination of whether a patient can safely undergo liver resection. Although dynamic (99m)Tc-mebrofenin hepatobiliary scintigraphy (HBS) is used to measure FRL function, 2-dimensional planar images lack the ability to assess segmental liver function. Modern SPECT/CT cameras combine dynamic (99m)Tc-mebrofenin HBS with additional SPECT and the anatomic information of the CT scan. The aim of this study was to evaluate the additional value of (99m)Tc-mebrofenin SPECT for the measurement of segmental liver function and liver functional volume. Preoperative CT volumetry and (99m)Tc-mebrofenin HBS with SPECT were performed in 36 patients undergoing liver resection. In 18 patients, postoperative (99m)Tc-mebrofenin HBS with SPECT was performed within 3 d after operation. Dual-head dynamic acquisitions were used to calculate FRL function using anterior and geometric mean (Gmean) datasets. Total and FRL functional liver volumes were measured by SPECT. Because of the anatomic position of the liver, the anterior projection resulted in an underestimation of FRL function in patients undergoing left hemihepatectomy. In patients with normal liver parenchyma, total functional liver volume was comparable to total liver volume measured by CT volumetry, indicating that (99m)Tc-mebrofenin SPECT is an accurate method to measure hepatic volume. In compromised livers, compared with normal livers, FRL function per cubic centimeter of liver volume was significantly less. In addition, liver function was not distributed homogeneously, with the segments to be resected relatively more affected. FRL function, measured by a combination of SPECT and dynamic HBS, was able to accurately predict actual postoperative remnant liver function. The Gmean dataset is recommended for the assessment of hepatic function by dynamic planar (99m)Tc-mebrofenin HBS. The combination of SPECT data with the dynamic uptake function measured by planar HBS provides valuable visible and quantitative information regarding segmental liver function and is an accurate measure for FRL function.

Endovascular Interventions following Intravenous Thrombolysis May Improve Survival and Recovery in Patients with Acute Ischemic Stroke: A Case-Control Study

Since the introduction of recombinant tissue plasminogen activator (rtPA) into clinical practice in the mid 1990s, no adjunctive treatment has further improved clinical outcomes in patients with ischemic stroke. The safety, feasibility, and efficacy of combining intravenous (IV) rtPA with endovascular interventions has been described; however, no direct comparative study has yet established whether endovascular interventions after IV rtPA are superior to IV rtPA alone. A retrospective case-control study was designed to address this issue. Between 2003 and 2006, 33 consecutive patients with acute ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) scores >/=10 were treated with IV rtPA in combination with endovascular interventions (IV plus intervention) at a tertiary care facility. Outcomes were compared with a control cohort of 30 consecutive patients treated with IV rtPA (IV only) at a comparable facility where endovascular interventions were not available. Baseline parameters were similar between the 2 groups. We found that the IV-plus-intervention group experienced significantly lower mortality at 90 days (12.1% versus 40.0%, P = .019) with a significantly greater improvement in NIHSS scores by the time of discharge or follow-up (P = .025). In the IV-plus-intervention group, patients with admission NIHSS scores between 10 and 15 and patients </=80 years of age showed the greatest improvement, with a significant change of the NIHSS scores from admission (P = .00015 and P = .013, respectively). In this small case-control study of patients with acute ischemic stroke and admission NIHSS scores >/=10, there was a suggestion of incremental clinical benefit among patients receiving endovascular interventions following standard administration of IV rtPA.

Dynamics of Excited-State Conformational Relaxation and Electronic Delocalization in Conjugated Porphyrin Oligomers

We have investigated the influence of nuclear geometric relaxation on the extent of the excited-state electronic delocalization in conjugated zinc porphyrin oligomers using ultrafast transient photoluminescence spectroscopy. By use of metal-coordinating templates that force the oligomers into specific geometries in solution we are able to distinguish clearly between relaxation effects arising from the two vibrational modes that preferentially couple to the electronic transitions in such materials, i.e., carbon-carbon bond stretches and inter-ring torsions. We find that light absorption generates an excited state that is initially strongly delocalized along the oligomer but contracts rapidly following vibrational relaxation of the nuclei along C-C stretch coordinates on the subpicosecond time scale. We are able to monitor such excitonic self-trapping effects by observing the extent to which the concomitant ultrafast rotation of the transition dipole moment is found to correlate with the degree of bending induced in the molecular backbone. We further demonstrate that interporphyrin torsional relaxation leads to a subsequent increase in the excited-state electronic delocalization on a longer time scale (approximately 100 ps). Such dynamic planarization of the molecular backbone is evident from the time-dependent increase in the overall emission intensity and red-shift in the peak emission energy that can be observed for wormlike flexible porphyrin octamers but not for torsionally rigidified cyclic or double-strand octamer complexes. These results therefore indicate that, following excitation, the initially highly delocalized excited-state wave function first contracts and then expands again along the conjugated backbone in accordance with the time periods for the vibrational modes coupled to the electronic transition.

Varying Appearance of Focal Nodular Hyperplasia in Nuclear Medicine Imaging

The focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor, which contains variable quantities of normal hepatic cellular elements: Kupffer cells, hepatocytes, bile ducts, and blood vessels. Two patients with suspicion of FNH were investigated by colloidal, blood pool, and hepatobiliary scintigraphy. Dynamic perfusion examination (with labeled RBCs), planar and SPECT studies were performed in all cases. Diagnosis was confirmed by histologic examination. We suggest the importance of combined imaging because of various appearance of the tumor. In our experience SPECT imaging after a planar study is a useful sequence, especially in small tumors in the exact location of activity.

Rodent brain imaging with SPECT/CT

We evaluated methods of imaging rat models of stroke in vivo using a single photon emission computed tomography (SPECT) system dedicated to small animal imaging (X-SPECT, Gamma Medica-Ideas, Northridge, CA). An animal model of ischemic stroke was developed for in vivo SPECT/CT imaging using the middle cerebral artery occlusion (MCAO) technique. The presence of cerebral ischemia was verified in ex vivo studies using triphenyltetrazolium chloride (TTC) staining. In vivo radionuclide imaging of cerebral blood flow was performed in rats following MCAO using dynamic planar imaging of 99mTc-exametazime with parallel hole collimation. This was followed immediately by in vivo radionuclide imaging of cerebral blood flow with 99mTc-exametazime in the same animals using 1-mm pinhole SPECT. Correlated computed tomography imaging was performed to localize radiopharmaceutical uptake. The animals were allowed to recover and ex vivo autoradiography was performed with separate administration of 99mTc-exametazime. Time activity curve of 99mTc-exametazime showed that the radiopharmaceutical uptake could be maintained for over 9 min. The activity would be expected to be relatively stable for a much longer period, although the data were only obtained for 9 min. TTC staining revealed sizable infarcts by visual observation of inexistence of TTC stain in infracted tissues of MCAO rat brains. In vivo SPECT imaging showed cerebral blood flow deficit in the MCAO model, and the in vivo imaging result was confirmed with ex vivo autoradiography. We have demonstrated a capability of imaging regions of cerebral blood flow deficit in MCAO rat brains in vivo using a pinhole SPECT dedicated to small animal imaging.

A Linogram/Sinogram Cross-Correlation Method for Motion Correction in Planar and SPECT Imaging

In this work, a correlation function based on linograms and sinograms of the projection data was introduced, implemented and evaluated in order to estimate and compensate for the patient motion. Parabolic fitting of the peak of the correlation function was utilized to improve in the motion-estimation task. In dynamic planar imaging, the method checked for motion via its separate frames similar to the SPECT work; on the other hand, in static planar imaging, the data acquisition protocol was first exchanged from static to the dynamic modality, followed by application of the motion-correction scheme, and a final combination via summation of the motion-compensated frames. The method was successfully evaluated in many cases. Our tests showed that in SPECT imaging, the time of motion starting in a specific projection and the duration of motion are very important in the motion detection process. Measuring relative error showed that the error in the images with presence of motion along the axis of patient bed was 21.1%, being reduced to 1.4% while the 24.4% error along the perpendicular axis to the patient bed was reduced to 1.5% with the inclusion of our motion correction scheme. Experimental results in planar imaging also demonstrated the ability of this method to reduce error in the maximum count from 40.7% to 9.7%, wherein intended sudden motion was introduced in static planar acquisition. Similarly, the error produced by gradual simulated motion was reduced from 37% to 1.6%. This method was clinically examined in the bone scan (static planar data) of an old man for an Osteomyelitis study, as well as in a kidney washout study (dynamic planar data) for a child. As a result, the motion artifacts shown in the images were reduced considerably

Comparison of the uptake of [123/125I]-2-iodo-d-tyrosine and [123/125I]-2-iodo-l-tyrosine in R1M rhabdomyosarcoma cells in vitro and in R1M tumor-bearing Wag/Rij rats in vivo

Recently, promising results concerning uptake in vivo in tumors of D-amino acids have been published. Therefore, we decided to evaluate the tumor uptake of the D-analogue of [(123)I]-2-iodo-L-tyrosine, a tracer recently introduced by our group into clinical trials. The uptake of 2-amino-3-(4-hydroxy-2-[(123/125)I]iodophenyl)-D-propanoic acid (2-iodo-D-tyrosine) was studied in vitro in LAT1-expressing R1M rat rhabdomyosarcoma cells and in vivo in R1M tumor-bearing Wag/Rij rats. The uptake of [(125)I]-2-iodo-L-tyrosine and [(125)I]-2-iodo-D-tyrosine into R1M cells was determined in appropriate buffers, allowing the study of the involved transport systems. In vivo, the biodistribution in R1M-bearing rats of [(123)I]-2-iodo-L-tyrosine and [(123)I]-2-iodo-D-tyrosine was performed by both dynamic and static planar imaging with a gamma camera. In in vitro conditions, the uptake of both [(125)I]-2-iodo-L-tyrosine and [(125)I]-2-iodo-D-tyrosine in the HEPES buffer was 25% higher in the presence of Na(+) ions. In the absence of Na(+) ions, [(125)I]-2-iodo-D-tyrosine was taken up reversibly in the R1M cells, with an apparent accumulation, probably for the larger part by the LAT1 system. Dynamic planar imaging showed that the uptake in the tumors of [(123)I]-2-iodo-D-tyrosine was somewhat lower than that of [(123)I]-2-iodo-L-tyrosine. At 30 min postinjection, the mean differential uptake ratio values of the L- and D-enantiomers are 2.5+/-0.7 and 1.7+/-0.6, respectively. Although the uptake of the D-isomer is lower, probably due to a faster clearance from the blood, the tumor-background ratio is the same as that of the l-analogue. A large part (75%) of [(125)I]-2-iodo-D-tyrosine in vitro and [(123)I]-2-iodo-D-tyrosine in vivo is reversibly highly taken up in R1M tumor cells by Na(+)-independent LAT transport systems, more likely by the LAT1. The clearance from the blood of [(123)I]-2-iodo-D-tyrosine in the rats is faster than that of the L-analogue, resulting in a slightly lower tumor uptake but with the same tumor-background ratio.

123/125I-labelled 2-iodo-L-phenylalanine and 2-iodo-D-phenylalanine: comparative uptake in various tumour types and biodistribution in mice

In vitro in the R1M cell model and in vivo in the R1M tumour-bearing athymic model, both [(123)I]-2-iodo-L: -phenylalanine and [(123)I]-2-iodo-D: -phenylalanine have shown promising results as tumour diagnostic agents for SPECT. In order to compare these two amino acid analogues and to examine whether the observed characteristics could be generalised, both isomers were evaluated in various tumour models. Transport type characterisation in vitro in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M cells with [(123)I]-2-iodo-L: -phenylalanine was performed using the method described by Shotwell et al. Subsequently, [(123)I]-2-iodo-L: -phenylalanine and [(123)I]-2-iodo-D: -phenylalanine tumour uptake and biodistribution were evaluated using dynamic planar imaging and/or dissection in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M inoculated athymic mice. Two-compartment blood modelling of the imaging results was performed. In vitro testing demonstrated that [(123)I]-2-iodo-L: -phenylalanine was transported in all tumour cell lines by LAT1. In all tumour models, the two amino acid analogues showed the same general biodistribution characteristics: high and specific tumour uptake and renal tracer clearance. Two-compartment modelling revealed that the D: -isomer showed a faster blood clearance together with a faster distribution to the peripheral compartment in comparison with [(123)I]-2-iodo-L: -phenylalanine. [(123)I]-2-iodo-L: -phenylalanine and its D: -isomer are promising tumour diagnostic agents for dynamic planar imaging. They showed a high and similar uptake in all tested tumours. [(123)I]-2-iodo-D: -phenylalanine showed better tracer characteristics concerning radiation dose to other organs.