Whole-body Planar Imaging Research Articles

In Vivo Molecular Imaging of Atherosclerotic Lesions in ApoE−/− Mice Using VCAM-1–Specific, 99mTc-Labeled Peptidic Sequences

Vascular cell adhesion molecule 1 (VCAM-1) plays a major role in the chronic inflammatory processes involved in vulnerable atherosclerotic plaque development. We previously showed that the (99m)Tc-labeled major histocompatibility complex 1-derived peptide B2702p bound specifically to VCAM-1 and allowed the ex vivo imaging of atherosclerotic lesions in Watanabe heritable hyperlipidemic rabbits. However, B2702p target-to-background ratio was suboptimal for the in vivo imaging of VCAM-1 expression in atherosclerotic lesions. To improve the target-to-background ratio, 20 derivatives of B2702p (B2702p1-B2702p20) were synthesized using the alanine scan methodology. We hypothesized that (99m)Tc-radiolabeled B2702p derivatives might allow the molecular imaging of VCAM-1 expression in an experimental model of atherosclerosis. A mouse model of focal atherosclerotic plaque development induced by left carotid artery ligation in apolipoprotein E double-knockout (ApoE(-/-)) mice was used (n = 82). (99m)Tc-B2702p and (99m)Tc-B2702p1-(99m)Tc-B2702p20 were injected intravenously in anesthetized animals 3 wk after the ligation. Whole-body planar imaging was performed for 3 h. SPECT imaging of 6 additional ligated ApoE(-/-) mice was also performed with (99m)Tc-B2702p1. The animals were then euthanized, and the biodistribution of (99m)Tc-labeled peptides was evaluated by γ-well counting of excised organs. Expression of VCAM-1 in the ligated and contralateral carotid arteries was evaluated by immunohistology. Robust VCAM-1 immunostaining was observed in the left carotid atherosclerotic lesions as a consequence of artery ligation, whereas no VCAM-1 expression was detected in the contralateral carotid artery. Among all evaluated peptides, (99m)Tc-B2702p1 exhibited the most favorable properties. By γ-well counting, there was a significant 2.0-fold increase in the (99m)Tc-B2702p1 left-to-right carotid artery activity ratio (2.6 ± 0.6) and a 3.4-fold increase in the left carotid-to-blood activity ratio (1.4 ± 0.4) in comparison to (99m)Tc-B2702p (1.3 ± 0.2 and 0.4 ± 0.1, respectively, P < 0.05 for both comparisons). Similarly, planar image quantification indicated a higher left-to-right carotid activity ratio in (99m)Tc-B2702p1- than in (99m)Tc-B2702p-injected mice (1.2 ± 0.1 vs. 1.0 ± 0.0, respectively, P < 0.05). Finally, a significantly higher (99m)Tc-B2702p1 activity in the left than in the right carotid artery was observed by SPECT imaging (2.2 ± 0.4 vs. 1.4 ± 0.3 cpm/mm(2)/injected dose, respectively, P < 0.05). (99m)Tc-B2702p1 is a potentially useful radiotracer for the in vivo molecular imaging of VCAM-1 expression in atherosclerotic plaques.

A phase I imaging and pharmacodynamic trial of CS-1008 in patients (pts) with metastatic colorectal cancer (mCRC).

2583 Background: Death receptor 5 (DR5) is a member of the TNFR superfamily that initiates the extrinsic apoptotic pathway. CS-1008 is a humanised, monoclonal IgG1 agonistic antibody (Ab) to human DR5 created by CDR grafting of the murine Ab TRA-8. The aim of this study was to investigate the impact of CS-1008 dose on biodistribution, quantitative tumor uptake and anti-tumor response in pts with mCRC. Methods: Pts with mCRC were treated with weekly IV CS-1008 in 5 non-sequential cohorts (Co). Different loading doses were used on days 1 and 8 (0.2 to 6 mg/kg), followed by a weekly dose of 2 mg/kg. D1 and D36 doses were trace-labeled with 111In, followed by whole-body planar and regional SPECT imaging over 10 days. Primary endpoints: initial biodistribution, pharmacokinetic (PK) and tumor uptake following single infusion; changes in biodistribution, PK and tumor uptake following sequential doses. Secondary endpoints: tumor response; changes in tumor metabolism by FDG-PET; serum apoptosis biomarkers and tumor response markers. Results: 19 pts (median age 64 yrs; M:F 11:8; 2-6 prior chemotherapy regimens) were enrolled as follows: Co 1, n=2; Co 2, n=4; Co 3, n=5; Co 4, n=3; and Co 5, n=5. Tumor uptake was variable: 7 pts had no uptake, 11 pts had uptake in all sites of disease but liver, 1 pt showed liver uptake. Tumor uptake and PK were not affected by dose or repeated drug administration. No anti-CS-1008 Ab responses were detected. DR5 expression in archived samples did not correlate with uptake or response. 111In‐CS‐1008 biodistribution showed gradual blood pool clearance and no abnormal uptake in normal tissue. Mean % change in SUVmax from baseline in lesions with uptake was higher than in those with no uptake. There were 8 SD, 1 PR and 10 PD. Duration of PR was 3.7 months (mo). Mean duration of SD was 4 mo. Disease control rate (SD + PR) in pts with uptake was 58% vs 28% of pts with no uptake. Lesions with no uptake were more likely to progress, with a PD risk of 3.4 times higher than those lesions with uptake. Conclusions: Tumor DR5 expression, assessed by 111In-CS-1008 imaging, revealed real-time heterogeneous DR5 expression and appeared to be a promising predictive imaging biomarker of clinical benefit in pts with mCRC receiving CS-1008. Clinical trial information: NCT01220999.

Photomultiplier Tube Artifacts on 67Ga-Citrate Imaging Caused by Loss of Correction Floods Due to an Off-Peak Status of One Head of a Dual-Head -Camera

γ-cameras use flood-field corrections to ensure image uniformity during clinical imaging. A loss or corruption of the correction data of one head of a dual-head camera can result in an off-peak artifactual appearance. We present our experience with the occurrence of such an incident on a (67)Ga scan. A patient was referred for a whole-body (67)Ga scan to evaluate for causes of neutropenic fever. Whole-body planar and static images of the head, chest, abdomen, pelvis, and lower extremities in multiple projections were obtained. Whole-body images showed decreased image quality on the anterior view obtained with detector 1 and an unremarkable posterior image obtained with detector 2. A problem with detector 2 was suspected, and additional static images were obtained after rotation of the detector heads. The posterior images taken with detector 1 showed photomultiplier tube outlines. The anterior images taken with detector 2 showed improved count and image quality. It was later found that the uniformity map for detector 2 had been lost and that this software malfunction led to the resulting imaging problem. When artifacts with an off-peak appearance are seen on scintigraphic images, evaluation of possible causes should include not only isotope window settings but also an incorrect or corrupted uniformity map.

99mTc-DMSA (V) in Evaluation of Osteosarcoma: Comparative Studies with 18F-FDG PET/CT in Detection of Primary and Malignant Lesions

To evaluate the role of 99mTc-DMSA (V) and [18F]FDG PET-CT in management of patients with osteosarcoma, 22 patients were included in our study. All patients underwent both 99mTc-DMSA (V) and whole-body [18F]FDG PET-CT scans within an interval of 1 week. 555–740 MBq of 99mTc-DMSA (V) was injected i.v. the whole-body planar, SPECT images of primary site and chest were performed after 3-4 hours. [18F]FDG PET-CT images were obtained 60 minutes after i.v. injection of 370 MBq of F-18 FDG. Both FDG PET-CT (mean SUVmax = 7.1) and DMSA (V) scans showed abnormal uptake at primary site in all the 22 patients (100% sensitivity for both). Whole-body PET-CT detected metastasis in 11 pts (lung mets in 10 and lung + bone mets in 1 patient). Whole-body planar DMSA (V) and SPECT detected bone metastasis in one patient, lung mets in 7 patients and LN in 1 patient. HRCT of chest confirmed lung mets in 10 patients and inflammatory lesion in one patient. 7 patients positive for mets on DMSA (V) scan had higher uptake in lung lesions as compared to FDG uptake on PET-CT. Three patients who did not show any DMSA uptake had subcentimeter lung nodule. Resuts of both 99mTc-DMSA (V) (whole-body planar and SPECT imaging) and [18F]FDG PET-CT were comparable in evaluation of primary site lesions and metastatic lesions greater than 1 cm. Though 99mTc-DMSA (V) had higher uptake in the lesions as compared to [18F]FDG PET-CT, the only advantage [18F]FDG PET-CT had was that it could also detect subcentimeter lesions.

Abstract 1755: Pretargeted radioimmunotherapy of an anti-CEA bispecific antibody and 177Lu-labeled peptide: a phase I study in patients with advanced colorectal cancer

Abstract Table of Contents * Pretargeted radioimmunotherapy of an anti-CEA bispecific antibody and 177Lu-labeled peptide: a phase I study in patients with advanced colorectal cancer * Abstract Objectives: Pretargeted radioimmunotherapy (PRIT) with bispecific monoclonal antibodies (bsMAb) in combination with a radiolabeled peptide reduces the radiation dose of conventional RIT to normal tissues by rapid tumor targeting and fast blood clearance of the radiolabeled molecule. In this phase I trial, PRIT was investigated in 20 patients with advanced colorectal cancer (CRC), using a humanized recombinant bsMAb, TF2, targeting carcinoembryonic antigen (CEACAM5) and the hapten-peptide, IMP288, which was radiolabeled with177Lu. The safety, pharmacokinetics, and tumor targeting of these agents were studied, by optimizing the dose schedule of the pretargeting system. Methods: We included four cohorts with five patients per cohort. We studied the interval between the bsMAb and peptide administration and its consequences for the blood clearance of the radiolabeled peptide (cohort 1: 5 days interval vs next cohorts: 1 day). We escalated TF2 dose to saturate tumor antigens (cohort 3: 150 mg TF2, vs other cohorts: 75 mg). Furthermore, we investigated the effect of labelling the same radioactivity doses to a lower peptide dose, which ideally would increase the fractional targeting to the tumors (cohort 4: 25 µg IMP288 vs other cohorts: 100 µg) A pre-therapy cycle with 111In-labeled IMP288 was used to predict the pharmacokinetics and tumor targeting of 177Lu-IMP288, and to assure safety of high 177Lu activity doses (3.7 GBq in cohort 1 and ≤ 7.4 GBq in cohorts 2-4). Toxicity was determined by NCI-CTC v3.0. Whole-body planar and SPECT images were acquired. Results: Toxicity was generally very mild, with only two patients showing grade 3-4 thrombocytopenia, and one with grade 3 dyspnea. Dose escalation did not increase toxicity. Rapid localization of the radiolabeled peptide in the tumor lesions was clearly visualized with scintigraphy within 1 h of injection, with excellent tumor-to-normal tissue ratios (&amp;gt;20 at 24 h after injection in all cohorts). Low absorbed radiation doses to the red bone marrow (&amp;lt;0.3 Gy) and kidneys (&amp;lt;6 Gy) were calculated for all cohorts. TF2 and 111In/177Lu-IMP288 cleared rapidly from the blood (&amp;lt;2%ID in the blood 1 day p.i. in all cohorts). Conclusion: These first results in man show that CEACAM5-expressing CRC can be safely, specifically and rapidly targeted with TF2 and 177Lu-IMP288, with limited toxicity, by pretargeted radioimmunotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1755. doi:1538-7445.AM2012-1755

Recombinant Human Thyroid-Stimulating Hormone Versus Thyroid Hormone Withdrawal in the Identification of Metastasis in Differentiated Thyroid Cancer with 131I Planar Whole-Body Imaging and 124I PET

Various studies have compared the detection of functioning residual thyroid tissue after thyroidectomy using radioiodine whole-body (WB) imaging following preparation of patients with injections of recombinant human thyroid-stimulating hormone (rhTSH) and thyroid hormone withdrawal (THW). However, metastases may have radiopharmacokinetics different from normal thyroid tissue. The objective of this study was to evaluate these 2 methods of patient preparation for the detection of metastases from differentiated thyroid cancer (DTC) using (131)I WB imaging and (124)I PET. A prospective study approved by the institutional review board was conducted at Washington Hospital Center from 2006 to 2010 recruiting patients who had DTC, were suspected of having metastasis from DTC (e.g., elevated thyroglobulin level without thyroglobulin antibodies, positive results on recent fine-needle aspiration, suspected enlarging mass, and abnormal findings suggesting metastasis on a diagnostic study) and were referred for (131)I WB dosimetry. All patients subsequently underwent both (131)I WB imaging and (124)I PET performed using the same preparation. All foci of uptake identified on these scans were categorized in a masked manner by consensus of 2 physicians in the following manner: 1, definite physiologic uptake or artifact; 2, most likely physiologic uptake or artifact; 3, indeterminate; 4, most likely locoregional metastases in the neck bed; 5, most likely distant metastases; or 6, definite distant metastases. Foci categorized as 4, 5, and 6 were considered positive for functioning metastases. Of 40 patients evaluated, 24 patients were prepared with rhTSH and 16 with THW. No statistical difference was noted between the 2 groups for any of the parameters evaluated, including serum thyroglobulin. The percentages of patients with positive foci detected on the rhTSH (131)I and THW (131)I WB scans were 4% (1/24) and 63% (10/16), respectively (P < 0.02). The number of foci detected on the rhTSH (131)I and THW (131)I WB scans were 2 and 58, respectively (P < 0.05). When (124)I PET was used for imaging, the percentages of patients with foci detected on the rhTSH and THW scans were 29% (7/24) and 63% (10/16), respectively (P < 0.03). The number of foci detected on the rhTSH and THW scans were 17 and 117, respectively (P < 0.03). Significantly more foci of metastases of DTC may be identified in patients prepared with THW than in patients prepared with rhTSH.

Incidental Diagnosis of Carcinoma of the Bladder Due to Uptake of (99m)Tc-MDP.

An 80-year-old male patient presented to the orthopaedist for evaluation of low backache. A bone scan was performed using 740 MBq (20 mCi) 99mTc-MDP. Whole-body planar images were acquired 3 h after injection (Fig. 1). The scan revealed normal physiological tracer uptake in skeletal system but irregular and heterogenous accumulation of tracer in the bladder (Fig. 2). To evaluate this abnormal accumulation further, the patient was given a dose of 40 mg furosemide and asked to drink plenty of water. He was instructed to void three to four times within 2–3 h. After 3 h, the urine became less radioactive. An SPECT-CT image of pelvis was acquired, and the images revealed intense multifocal uptake in multiple bladder polyps (Figs. 3, ​,4).4). Urine cytology was done, which subsequently revealed malignant cells. Further evaluation with cystoscopic biopsy confirmed transitional cell carcinoma (TCC) of the bladder. Intraoperatively multiple broad based polyps were seen in the dome of the bladder. Transurethral resection of the bladder tumors was done, and histopathology revealed arborizing islands and cords of atypical urothelial cells dissecting and infiltrating the bladder musculature (Fig. 5a, b). H&E photomicrograph at higher magnification (×200) showed mitosis and focal squamous differentiation (Fig. 5c). Fig. 1 Anterior and posterior whole-body bone scan showing physiological uptake in skeleton but irregular accumulation in bladder Fig. 2 99mTc-MDP bone scan of anterior and posterior pelvic spot views highlighting the irregular accumulation in the bladder Fig. 3 CT showing multiple bladder polyps; SPECT showing uptake in those polyps and the fused SPECT/CT image Fig. 4 Transaxial SPECT-CT images showing intense 99mTc-MDP uptake in the bladder polyps and less radioactive urine. Corresponding CT images showing multiple bladder polyps Fig. 5 a, b H&E photomicrograph at low magnification (×40) showing arborizing islands and cords of atypical urothelial cells dissecting and infiltrating the bladder musculature. c Photomicrograph at higher magnification (×200) showing ... Soft tissue uptake of 99mTc-MDP is described in various benign and malignant conditions [1–4]. It is known to accumulate in adenocarcinoma of lung, primary breast cancer, and colonic carcinoma among others. The actual mechanism of uptake in the malignant lesion is not known. The postulated causes of 99mTc-MDP uptake in extraosseous neoplasms are numerous and include tumor vascularity, inflammation, local pH factors, altered calcium metabolism, hormonal influences and cell wall damage [4, 5]. Our case shows that TCC of the bladder was incidentally diagnosed due to MDP uptake in multiple bladder polyps detected on a bone scan done for low backache in an 80-year-old man. This report also shows the importance of delayed imaging after diuretic administration.

Estimation of absorbed dose to the kidneys in patients after treatment with 177Lu-octreotate: comparison between methods based on planar scintigraphy.

BackgroundLu-[DOTA0, Tyr3]-octreotate (177Lu-octreotate) is used to treat neuroendocrine tumors with high somatostatin-receptor expression. 177Lu-octreotate is mainly excreted via the kidneys, but to some extent, accumulates in the kidney cortex due to, e.g., tubular reabsorption. Renal toxicity is one of the main limiting factors in 177Lu-octreotate treatment. Further knowledge of the biodistribution and dosimetry of 177Lu-octreotate in individual patients is needed. The aim of this study was to estimate the absorbed dose to the kidneys and compare the results obtained with planar imaging and different dosimetric methods: (1) conjugate-view (CV) method using patient-specific kidney sizes, (2) PA method, based on posterior images only, (3) CV method with reduced number of time points (CVreduced data), and (4) CV method using standard kidney sizes (CVstandard size).MethodsTotally, 33 patients each received 3.4 to 8.2 GBq of 177Lu-octreotate up to five times, with infusion of lysine and arginine to block the renal uptake. Whole-body planar gamma camera images were acquired on days 0, 1, 2, and 7. The 177Lu concentration in the kidneys was determined by the CV method, and the absorbed dose was estimated with patient-specific organ sizes. Comparison to the CV method was made using posterior images only, together with the influence of the number of time points and with standard organ sizes.ResultsLarge interindividual variations were found in the time-activity curve pattern and in the absorbed dose to the kidneys using the CV method: 0.33 to 2.4 Gy/GBq (mean = 0.80 Gy/GBq, SD = 0.30). In the individual patient, the mean deviation of all subsequent kidney doses compared to that of the first administration was 1% (SD = 19%) and 5% (SD = 23%) for the right and left kidneys, respectively. Excluding data for day 7 resulted in large variations in the absorbed dose.ConclusionLarge interindividual variations in kidney dose were found, demonstrating the need for patient-specific dosimetry and treatment planning.

Current activities in the ICRP concerning estimation of radiation doses to patients from radiopharmaceuticals for diagnostic use

A Task Group within the ICRP Committees 2 and 3 is continuously working to improve absorbed dose estimates to patients investigated with radiopharmaceuticals. The work deals with reviews of the literature, initiation of new or complementary studies of the biokinetics of a compound and dose estimates. Absorbed dose calculations for organs and tissues have up to now been carried out using the MIRD formalism. There is still a lack of necessary biokinetic data from measurements in humans. More time series obtained by nuclear medicine imaging techniques such as whole-body planar gamma-camera imaging, SPECT or PET are highly desirable for this purpose. In 2008, a new addendum to ICRP Publication 53 was published under the name of ICRP Publication 106 containing biokinetic data and absorbed dose information to organs and tissues of patients of various ages for radiopharmaceuticals in common use. That report also covers a number of generic models and realistic maximum models covering other large groups of substances (e.g. "123I–brain receptor substances"). Together with ICRP Publication 80, most radiopharmaceuticals in clinical use at the time of publication were covered except the radioiodine labeled compounds for which the ICRP dose estimates are still found in Publication 53. There is an increasing use of new radiopharmaceuticals, especially PET-tracers and the TG has recently finished its work with biokinetic and dosimetric data for 18F-FET, 18F-FLT and 18F-choline. The work continues now with new data for 11C-raclopride, 11C-PiB and 123I-ioflupan as well as re-evaluation of published data for 82Rb-chloride, 18F-fluoride and radioiodide. This paper summarises published ICRP-information on dose to patients from radiopharmaceuticals and gives some preliminary data for substances under review.

Beware of the focal uptake at the ischium on the bone scan in prostate cancer

The isotope bone scan is routinely used in the management of prostate cancer as the skeleton is the second most common area of metastasis after lymph nodes. A classic site of involvement in the pelvis is the ischium, and the aim of this study was to assess the value of single-photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with focal ischial uptake on the planar scan. This was a retrospective study of consecutive 150 patients with prostate cancer who were referred for a whole-body bone scan between August 2007 and 2008. Two experienced nuclear medicine consultants along with a musculoskeletal radiologist reviewed the scans. Sixty-eight patients were diagnosed with widespread metastases and 46 patients showed typical degenerative disease changes on planar whole-body imaging. SPECT/CT imaging was done in 36 patients to clarify the diagnosis in areas of indeterminate uptake noted on planar whole-body imaging. Ten of these 36 patients who had focal increased ischial uptake were included in the study. Only three of these 10 patients were diagnosed as having a metastatic lesion with the presence of an enthesopathy, a common finding. Isolated focal uptake in the ischium is a relatively common finding in patients with prostate cancer and there is concern that this, on occasion, could be misinterpreted as metastasis. SPECT/CT imaging has an important role in differentiating a benign from a malignant lesion.

Solitary Phalangeal Metastasis of Renal Cell Carcinoma on Bone Scintigram

Renal cell carcinoma is known to cause lytic metastasis at various sites including axial and appendicular skeleton. However, it is unusual to find an isolated metastasis of renal cell carcinoma in the distal extremity on bone scintigraphy. A 70-year-old woman with renal cell carcinoma was referred to the Nuclear Medicine Department for a bone scintigram to exclude metastasis. The whole-body planar images were unremarkable, but the local views of the hands demonstrated a solitary metastasis in the middle phalanx of the finger. This rare experience illustrates the need for including local views of extremities in a standard whole-body study.

Comparison of Single Time-Point [111-In] Pentetreotide SPECT/CT With Dual Time-Point Imaging of Neuroendocrine Tumors

to determine whether single time-point single-photon emission computed tomography-computed tomography (SPECT/CT) somatostatin receptor imaging can replace traditional dual time-point planar and SPECT somatostatin receptor scintigraphy for evaluation of neuroendocrine tumors. twenty-four patients (9 males, 15 females; mean age: 56 years; range: 14-82 years) underwent [111-In] pentetreotide scintigraphy, with planar whole-body images acquired at 24 and 48 hours after injection and abdominal SPECT/CT at 24 hours postinjection. Two blinded readers independently interpreted each study, using single time-point (24 hours planar and SPECT/CT) and separately using dual time-point (24- and 48-hours planar, and 24-hour SPECT without CT) image information. Consensus interpretations were compared with surgical pathology, or clinical and radiologic follow-up for at least 12 months. Interobserver agreement was excellent (κ = 0.86) for single time-point imaging, and good (κ = 0.56) with dual time-point imaging. After consensus review, single time-point imaging identified pathologic lesions in 11 of 12 subjects with diagnosis of NET at follow-up, and in 0 of 12 subjects without NET (sensitivity 92%; specificity 100%). Dual time-point imaging performed similarly, but missed an additional NET case (sensitivity 83%; specificity 100%). After review of SPECT/CT, the readers considered that additional 48 hours imaging was not necessary in the majority of cases, indicating high degree of confidence with the single time-point imaging. [111-In] pentetreotide SPECT/CT imaging at 24 hours identifies pathologic disease sites and distinguishes physiologic activity equally well compared to traditional strategies using 2 imaging days. Routine use of SPECT/CT will allow single time-point imaging without loss of diagnostic accuracy, enhancing patient convenience, and clinical throughput.

90Y Bremsstrahlung Imaging for Absorbed-Dose Assessment in High-Dose Radioimmunotherapy

This feasibility study demonstrates (90)Y quantitative bremsstrahlung imaging of patients undergoing high-dose myeloablative (90)Y-ibritumomab treatment. The study includes pretherapy (111)In SPECT/CT and planar whole-body (WB) imaging at 7 d and therapy (90)Y SPECT/CT at 6 d and (90)Y WB imaging at 1 d. Time-activity curves and organ-absorbed doses derived from (90)Y SPECT images were compared with pretherapy (111)In estimates. Organ activities derived from (90)Y WB images at the first day were compared with corresponding pretherapy estimates. Pretherapy (111)In images from 3 patients were similar to the (90)Y images. Differences between absorbed-dose estimates from pretherapy (111)In and (90)Y therapy were within 25%, except for the lungs. Corresponding activity differences derived from WB images were within 25%. Differences were ascribed to incomplete compensation methods and real differences in pharmacokinetics between pretherapy and therapy. Quantitative bremsstrahlung imaging to estimate organ activities and absorbed doses is feasible.

124I Positron Emission Tomography Versus131I Planar Imaging in the Identification of Residual Thyroid Tissue and/or Metastasis in Patients Who Have Well-Differentiated Thyroid Cancer

(124)I emits a positron and can be imaged with a positron emission tomography (PET) scanner. The objective of this study was to compare the ability of diagnostic (124)I PET images versus (131)I planar whole-body imaging in detecting residual thyroid tissue and/or metastatic well-differentiated thyroid cancer (WDTC). Patients were recruited prospectively for this study who (i) had WDTC, (ii) were suspected of having metastatic WDTC, and (iii) were referred for (131)I whole-body dosimetry. The prescribed activity was 1-2 mCi (37-74 MBq) and 1.7 mCi (62.9 MBq) for (131)I and (124)I, respectively. For each image, one blinded reader (D.V.N.) categorized every focus of (131)I and (124)I radioiodine uptake as 1 = definite physiological uptake/artifact, 2 = most likely physiological uptake/artifact, 3 = indeterminate, 4 = residual thyroid tissue/metastases in the neck/bed, 5 = most likely metastases, or 6 = definite metastases. Foci categorized as 4, 5, or 6 were considered positive. When available, foci categorized as 4, 5, or 6 were correlated with other diagnostic studies. Of the 25 patients, 8 patients (32%) had more positive foci on (124)I images than on (131)I, of which 3 patients to date have had metastases confirmed in one or more of the additional positive (124)I foci. (124)I demonstrated the same number of foci as on (131)I in 16 patients (14 with no positive foci, and 2 with two positive and five positive foci each). One patient had one additional positive focus on (131)I not seen on (124)I, which has not yet been confirmed as a metastasis. A total of 97 positive foci were identified on either (124)I or (131)I. (124)I identified 49 positive foci not seen with (131)I, and (131)I identified one positive focus not seen with (124)I. Relative to (131)I planar whole-body imaging, (124)I PET identified as many as 50% more foci of radioiodine uptake suggestive of additional residual thyroid tissue and/or metastases in as many as 32% more patients who had WDTC.

SPECT/CT stabilizes the interpretation of somatostatin receptor scintigraphy findings: a retrospective analysis of inter-rater agreement

Correlating the anatomical information from CT with the functional information from SPECT improves diagnostic accuracy of somatostatin-receptor-scintigraphy (SRS) in patients with neuroendocrine tumors (NET). The aim of the present study was to investigate the impact of dual modality SPECT/CT on the inter-rater agreement in SRS. Twenty-five unselected patients with suspected or histologically proven NET in whom whole body planar imaging and low-dose SPECT/CT had been performed after injection of 200 MBq In-111-octreotide were included retrospectively. Images were interpreted independently by 2 nuclear medicine physicians, an experienced one and an inexperienced one. Both readers first re-evaluated the planar whole-body images alone, then added the SPECT images, and finally the CT-images. Lesions with pathologically increased tracer uptake were categorized according to the following 3-point score: equivocal, probably pathologic, and definitely pathologic. Cohen's linear-weighted kappa coefficient kappa was used to quantify inter-rater agreement. A total number of 50 lesions were described in 23 of the 25 patients. The two readers showed only moderate agreement in the interpretation of the planar findings (kappa = 0.593). Agreement improved to substantial by adding SPECT (kappa = 0.736) and to very good by adding SPECT/CT (kappa = 0.860). SPECT/CT resulted in up-staging of 18% of the lesions and down-staging of 12% compared to planar + SPECT (experienced reader). In addition, SPECT/CT tended to reduce the frequency of indefinite scores (equivocal, probably pathologic), from 18% in planar + SPECT to 6% (p = 0.065). Change of lesion localization by SPECT/CT tended to contribute to the change of lesion score (p = 0.055). The present results suggest that low-dose SPECT/CT stabilizes report quality in SRS by improving inter-rater agreement.

Distribution and Dynamics of 99mTc-Pertechnetate Uptake in the Thyroid and Other Organs Assessed by Single-Photon Emission Computed Tomography in Living Mice

(99m)Tc pertechnetate is a well-known anion, used for clinical imaging of thyroid function. This gamma emitter is transported by the sodium iodide symporter but is not incorporated into thyroglobulin. Scintigraphy using (99m)Tc pertechnetate or (123)iodide represents a powerful tool for the study of sodium iodide symporter activity in different organs of living animal models. However, in many studies that have been performed in mice, the thyroid could not be distinguished from the salivary glands. In this work, we have evaluated the use of a clinically dedicated single-photon emission computed tomography (SPECT) camera for thyroid imaging and assessed what improvements are necessary for the development of this technique. SPECT of the mouse neck region, with pinhole collimation and geometric calibration, was used for the individual measurement of (99m)Tc pertechnetate uptake in the thyroid and the salivary glands. Uptake in the stomach was studied by planar whole-body imaging. Uptake kinetics and biodistribution studies were performed by sequential imaging. This work has shown that thyroid imaging in living mice can be performed with a SPECT camera originally built for clinical use. Our experiments indicate that (99m)Tc pertechnetate uptake is faster in the thyroid than in the salivary glands and the stomach. The decrease in (99m)Tc pertechnetate uptake after injection of iodide or perchlorate as competitive inhibitors was also studied. The resulting rate decreases were faster in the thyroid than in the salivary glands or the stomach. We have shown that a clinically dedicated SPECT camera can be used for thyroid imaging. In our experiments, SPECT imaging allowed the analysis of (99m)Tc pertechnetate accumulation in individual organs and revealed differences in uptake kinetics.

Whole Body and Cardiac Metaiodobenzylguanidine Kinetics in Parkinson Disease and Multiple System Atrophy

This study investigates whether combined analysis of I-123 metaiodobenzylguanidine (MIBG) kinetics in the heart and in the whole body can improve the accuracy of differential diagnosis between idiopathic Parkinson disease (PD) and a Parkinson variant of multiple system atrophy (MSA-P). A total of 30 patients with clinical suspicion of PD (n = 16) or MSA-P (n = 14) underwent MIBG whole-body planar imaging. Final diagnosis was confirmed at follow-up. Images were collected 30 minutes and 4 hours after tracer injection. Myocardial uptake was evaluated by measuring heart/mediastinum (H/M) ratio and the percent fraction of the injected dose retained by the heart (calculated by whole-body counts). Tracer washout was measured from both the heart and the whole body. H/M ratio was lower in PD than in MSA-P at early imaging (1.32 +/- 0.21 vs. 1.81 +/- 0.46, respectively, P < 0.01), although a large overlap in individual data was observed. By contrast, % of injected dose taken up by the heart documented a large difference between PD and MSA-P (0.97% +/- 0.51% vs. 1.91% +/- 0.66% of the dose, P < 0.01), and a very small overlap in individual values. There was no difference in the heart washout between the 2 Groups (31% +/- 13% vs. 32% +/- 15%, P = 0.9), while tracer loss from the whole body was higher in PD than in MSA-P (29% +/- 12% vs. 19% +/- 10%, P < 0.01). PD and its correlated global postganglionic dysfunction alter MIBG kinetics in the heart and in the whole body. Image analysis accounting for tracer kinetics in the whole body may improve the diagnostic accuracy of this test in patients with suspected PD or MSA-P.

Arterial Wall Dosimetry for Non-Hodgkin Lymphoma Patients Treated with Radioimmunotherapy

Tumors in non-Hodgkin lymphoma (NHL) patients are often proximal to the major blood vessels in the abdomen or neck. In external-beam radiotherapy, these tumors present a challenge because imaging resolution prevents the beam from being targeted to the tumor lesion without also irradiating the artery wall. This problem has led to potentially life-threatening delayed toxicity. Because radioimmunotherapy has resulted in long-term survival of NHL patients, we investigated whether the absorbed dose (AD) to the artery wall in radioimmunotherapy of NHL is of potential concern for delayed toxicity. SPECT resolution is not sufficient to enable dosimetric analysis of anatomic features of the thickness of the aortic wall. Therefore, we present a model of aortic wall toxicity based on data from 4 patients treated with (131)I-tositumomab. Four NHL patients with periaortic tumors were administered pretherapeutic (131)I-tositumomab. Abdominal SPECT and whole-body planar images were obtained at 48, 72, and 144 h after tracer administration. Blood-pool activity concentrations were obtained from regions of interest drawn on the heart on the planar images. Tumor and blood activity concentrations, scaled to therapeutic administered activities-both standard and myeloablative-were input into a geometry and tracking model (GEANT, version 4) of the aorta. The simulated energy deposited in the arterial walls was collected and fitted, and the AD and biologic effective dose values to the aortic wall and tumors were obtained for standard therapeutic and hypothetical myeloablative administered activities. Arterial wall ADs from standard therapy were lower (0.6-3.7 Gy) than those typical from external-beam therapy, as were the tumor ADs (1.4-10.5 Gy). The ratios of tumor AD to arterial wall AD were greater for radioimmunotherapy by a factor of 1.9-4.0. For myeloablative therapy, artery wall ADs were in general less than those typical for external-beam therapy (9.4-11.4 Gy for 3 of 4 patients) but comparable for 1 patient (32.6 Gy). Blood vessel radiation dose can be estimated using the software package 3D-RD combined with GEANT modeling. The dosimetry analysis suggested that arterial wall toxicity is highly unlikely in standard dose radioimmunotherapy but should be considered a potential concern and limiting factor in myeloablative therapy.

Autoradiography study and SPECT imaging of reporter gene HSV1-tk expression in heart

To demonstrate the feasibility and optimal conditions of imaging herpes simplex virus 1-thymidine kinase (HSV1-tk) gene transferred into hearts with (131)I-2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil ((131)I-FIAU) using autoradiography (ARG) and single photon emission computed tomography (SPECT) in animal models. HSV1-tk inserted into adenovirus vector (Ad5-tk) and adenovirus (Ad5-null) was prepared. Rats or rabbits were divided into a study group receiving intramyocardial injection of Ad5-tk, and a control group receiving Ad-null injection. In the study group of rats, two sets of experiments, time-course study and dose-dependence study, were performed. In time-course experiments, rats were injected with (131)I-FIAU on Days 1, 2, 3, 5 and 7, after transfection of 1x10(8) pfu Ad5-tk, to study the feasibility and suitable time course for reporter gene imaging. In dose-dependence study, various titers of Ad5-tk (5x10(8), 1x10(8), 5x10(7) and 1x10(7) pfu) were used to determine the threshold and optimal viral titer needed for detection of gene expression. The gamma counts of hearts were measured. The rat myocardium was analyzed by ARG and reverse transcriptase-polymerase chain reaction (RT-PCR). SPECT whole-body planar imaging and cardiac tomographic imaging were performed in the rabbit models. From the ARG images, rats injected with Ad5-tk showed significant (131)I-FIAU activity in the anterolateral wall compared with background signals seen in the control Ad5-null rats. In time-course study, the highest radioactivity in the focal myocardium could be seen on Day 1, and then progressively declined with time. In dose-dependence study, the level of (131)I-FIAU accumulation in the transfected myocardium declined with the decrease of Ad viral titers. From the ARG analysis and gamma counting, the threshold viral titer was 5x10(7) pfu, and the optimal Ad titer was 1x10(8) pfu. The ARG images in region of interest-derived semi-quantitative study correlated well with ex vivo gamma counting and mRNA levels from RT-PCR analysis. The gamma counting and RT-PCR also correlated well with each other in both sets of experiments. Both SPECT planar and tomographic images showed clear uptake of (131)I-FIAU in the anterolateral wall where Ad5-tk was injected. The study confirmed the feasibility of cardiac SPECT reporter gene imaging with HSV1-tk as a reporter gene and (131)I-FIAU as a reporter probe. The optimal Ad5-tk titer for imaging was 1x10(8) pfu and the optimal imaging time was 1-2 days after gene transfer. Thus, the imaging of HSV1-tk transgene expression in the heart is feasible and may be used for the noninvasive SPECT imaging of gene therapy in cardiac diseases.

A gamma camera count rate saturation correction method for whole-body planar imaging

Whole-body (WB) planar imaging has long been one of the staple methods of dosimetry, and its quantification has been formalized by the MIRD Committee in pamphlet no 16. One of the issues not specifically addressed in the formalism occurs when the count rates reaching the detector are sufficiently high to result in camera count saturation. Camera dead-time effects have been extensively studied, but all of the developed correction methods assume static acquisitions. However, during WB planar (sweep) imaging, a variable amount of imaged activity exists in the detector's field of view as a function of time and therefore the camera saturation is time dependent. A new time-dependent algorithm was developed to correct for dead-time effects during WB planar acquisitions that accounts for relative motion between detector heads and imaged object. Static camera dead-time parameters were acquired by imaging decaying activity in a phantom and obtaining a saturation curve. Using these parameters, an iterative algorithm akin to Newton's method was developed, which takes into account the variable count rate seen by the detector as a function of time. The algorithm was tested on simulated data as well as on a whole-body scan of high activity Samarium-153 in an ellipsoid phantom. A complete set of parameters from unsaturated phantom data necessary for count rate to activity conversion was also obtained, including build-up and attenuation coefficients, in order to convert corrected count rate values to activity. The algorithm proved successful in accounting for motion- and time-dependent saturation effects in both the simulated and measured data and converged to any desired degree of precision. The clearance half-life calculated from the ellipsoid phantom data was calculated to be 45.1 h after dead-time correction and 51.4 h with no correction; the physical decay half-life of Samarium-153 is 46.3 h. Accurate WB planar dosimetry of high activities relies on successfully compensating for camera saturation which takes into account the variable activity in the field of view, i.e. time-dependent dead-time effects. The algorithm presented here accomplishes this task.