Software-Based Hybrid Perfusion SPECT/CT Provides Diagnostic Accuracy When Other Pulmonary Embolism Imaging Is Indeterminate.

PURPOSE: To investigate the diagnostic performance of perfusion single-photon emission computed tomography/computed tomography (Q-SPECT/CT) in patients suspected to have pulmonary embolism (PE) but with indeterminate computed tomographic pulmonary angiography (CTPA) or planar ventilation/perfusion (V/Q) scans. METHODS: This retrospective study included two groups of patients. Group I consisted of 49 patients with nondiagnostic CTPA. These 49 patients underwent subsequent V/Q scans. Further Q-SPECTs were obtained in patients with indeterminate planar images and fused with existing CTPA. Group II consisted of 182 non-CTPA patients with indeterminate V/Q scans. These 182 patients underwent further Q-SPECT and separate noncontrast low-dose CT chest. Fusion Q-SPECT/CT scans were obtained through FDA-approved software and interpreted according to published criteria as positive, negative, or indeterminate for PE. Upon retrospective analyses, the final diagnosis was made using composite reference standards including all available clinical and imaging information for at least 6-month follow-up. RESULTS: In group I patients, 1 was positive, 24 were negative, and another 24 (49 %, 24/49) were indeterminate. In the subsequent 24 Q-SPECT/CTPAs, 4 were positive, 19 were negative, and 1 was indeterminate (4.2 %, 1/24). In group II patients, 9 (4.9 %, 9/182) were indeterminate, 33 were positive, and 140 were negative. The combined nondiagnostic rate for Q-SPECT/CT was only 4.9 % (10/206). There was six false-negative and one false-positive Q-SPECT/CT examinations. The sensitivity, specificity, and positive and negative predictive value of Q-SPECT/CT were 85.7 % (36/42), 99.4 % (153/154), 97.3 % (36/37) and 96.2 % (153/159), respectively. CONCLUSIONS: Q-SPECT/CT improves the diagnostic rate with promising accuracy in diagnosing PE that yields a satisfactory clinical verdict, especially when the CTPA and planar V/Q scan are indeterminate.

Case study of Tc-99m HMPAO brain SPECT imaging in a patient with hepatic encephalopathy and carotid artery stenosis.

A patient with hepatic encephalopathy is described. An initial SPECT using Tc-99m HMPAO was performed to evaluate relative brain perfusion. The initial brain SPECT images revealed decreased perfusion in the left frontal temporal lobe region. A subsequent carotid Doppler study revealed left-sided carotid artery stenosis. After appropriate medical treatment for elevated NH3 levels and reversal of the patient's symptoms, repeat SPECT brain images showed a normal pattern of activity. The possible causes and significance for these image findings are discussed.

The role of indium-111 radioimmunoscintigraphy in post-radical retropubic prostatectomy management of prostate cancer patients.

Indium-111 radioimmunoscintigraphy (RIS) has an increasing role in the treatment of prostate cancer and is most commonly performed at this disease site using labeled monoclonal antibody against prostate-specific membrane antigen. There are many limitations of RIS, including low spatial resolution, low diagnostic yield and limited availability. Despite these limitations, the efficacy of RIS has been demonstrated in many clinical studies, including multi-institutional investigations. The highest sensitivity and specificity of RIS appears to be in the post-radical retropubic prostatectomy (post-RRP) setting. RIS has recently been explored for its role in clinical radiotherapy decision-making, and was found to have a significant impact in selecting patients for radiotherapy and for the general radiotherapy treatment volume definition. RIS has also recently been explored for its role in radiotherapy planning and was found to impact clinical target volume design. However, manual editing of the RIS volume is still necessary when projected into the radiotherapy-planning scan, as there is often overlap in the RIS-defined uptake regions with normal structures (rectum, bladder and symphysis bone marrow). The impact of RIS on biochemical control has been explored, with studies in this area yielding conflicting results. It appears that the maximum impact of RIS is possible when areas of labeled antibody uptake regions are co-registered with the radiotherapy-planning computed tomography scan. The larger RIS-guided target volumes do not appear to be prohibitive in increasing radiotherapy-related toxicity. Future directions of the use of RIS for post-RRP prostate cancer are discussed.

Complete eradication of hepatic metastasis from colorectal cancer by Yttrium-90 SIRT.

Yttrium-90 (Y-90) radioembolization, also known as selective internal radiation therapy (SIRT), is a regional hepatic therapy used in the treatment of unresectable colorectal cancer (CRC) liver metastases. In SIRT, Y-90 impregnated microspheres are injected into the VASCULAR SUPPLY of hepatic tumor, leading to selective irradiation and necrosis of tumor TISSUE. While several studies demonstrate improved local control and survival with SIRT, the specific indications for this therapy have yet to be defined. Typically, SIRT is given in combination with chemotherapy as multimodal treatment for unresectable hepatic CRC. However, it has also found increasing use as a salvage therapy in chemo-refractory patients. Herein, the authors describe their experience with SIRT as "stand alone" therapy in a surgically-prohibitive, chemotherapy naive patient with hepatic CRC metastasis. The results suggest that Y-90 SIRT may have potential applications beyond its usual role as a palliative or salvage therapy for unresectable hepatic CRC.

Postprostatectomy target-normal structure overlap volume differences using computed tomography and radioimmunoscintigraphy images for radiotherapy treatment planning.

PURPOSE: The purpose of this study was to analyze regions of uptake in normal structures on postprostatectomy radioimmunoscintigraphy (RIS) images by evaluating differences in the overlap volumes of prostate fossa clinical target volume (CTV) and planning target volume (PTV) using correlative computed tomography (CT) images. MATERIALS AND METHODS: The electronic records of 13 patients who received external beam radiotherapy postprostatectomy and who underwent a vessel-based RIS/CT registration were reviewed. For each patient, the RIS-defined CTV (CTV(RIS)) was compared (in terms of the overlap volume with the surrounding bladder, rectum, pubic symphysis, and penile bulb) with the CT-defined CTV(pre) before this registration and also with CTV(post) (the final target volume used for treatment). Similar analyses were done for PTV(RIS), PTV(pre), and PTV(post) defined in each case to be the corresponding CTV + 1-cm margin. RESULTS: CTV(RIS) overlapped significantly more with the bladder, rectum, and symphysis, but not with the penile bulb, than did either the CTV(pre) or CTV(post). However, the corresponding PTV analyses revealed no significant differences between any of the overlap volumes of any of the PTVs with the bladder, rectum, and penile bulb, but did reveal a significant difference between the PTV(RIS) and PTV(post) overlap volumes with the symphysis compared with PTV(pre) overlap volumes with the symphysis. CONCLUSIONS: On RIS images, there appear to be areas of uptake in the bladder, rectum, and pubic symphysis but not the penile bulb; however, the dosimetric consequences of this uptake for radiation treatment planning are minimal on the bladder, rectum, and penile bulb, but require segmentation for dose reduction to the pubic symphysis.

Radioimmunoscintigraphy for postprostatectomy radiotherapy: analysis of toxicity and biochemical control.

UNLABELLED: Our goal was to evaluate the role of radioimmunoscintigraphy (RIS) directed against prostate-specific membrane antigen (PSMA) in influencing postprostatectomy radiotherapy (RT) toxicity and biochemical control. METHODS: The records of 107 postprostatectomy RT patients were reviewed. The group for whom no RIS scan was obtained (group A, n = 54) was identified as was the group for whom a RIS scan was obtained (group B, n = 53). Group B was further subdivided into those who had a RIS and CT-scan correlation to aid in treatment planning (subgroup B1, n = 40) versus those who did not (subgroup B2, n = 13). Gastrointestinal (GI) and genitourinary (GU) toxicities were reviewed for each of these groups and subgroups and compared. Biochemical failures (defined as 2 successive PSA rises after a nadir of >or=0.2 ng/mL) were identified to generate biochemical failure-free survival (BFFS) curves for each of the groups and subgroups. RESULTS: No significant differences in late toxicity were observed between any group or subgroup. However, acute GI toxicity was higher in group B versus group A (P = 0.026), and acute GU toxicity was higher in subgroup B2 versus subgroup B1 (P = 0.050). Overall, most toxicity was grade 1 or 2; only one case of grade 3 toxicity and no cases of grade 4 or 5 toxicity were observed. Three-year BFFS was higher for group B versus group A (80.7% vs. 75.5%) and for subgroup B1 versus subgroup B2 (84.5% vs. 71.6%). On multivariate analysis of pretreatment (age, race), surgical/staging (stage, grade, margin status, extracapsular extension, lymph node status, seminal vesicle invasion, post-radical retropubic prostatectomy [RRP] prostate-specific antigen [PSA] nadir, maximum post-RRP PSA, and RRP-to-RT interval), and treatment (hormone therapy, RT dose, RT technique, RIS scan, and RIS/CT correlation) factors on BFFS, the only covariate reaching significance was RIS/CT correlation (P = 0.042). CONCLUSION: A small BFFS advantage was observed in patients for whom RIS was used to guide RT decision making and treatment planning; however, this advantage only reached significance in this study for those for whom the RIS/CT correlation was used to guide target definition. The improved PSA control using RIS was achieved with a small increase in acute toxicity but with no observed change in late toxicity. These findings can serve as the basis for prospective studies in this area of investigation.

Influence of radioimmunoscintigraphy on postprostatectomy radiotherapy treatment decision making.

UNLABELLED: The aim of this study was to evaluate the role of radioimmunoscintigraphy (RIS) directed against prostate-specific membrane antigen (PSMA) in influencing postradical retropubic prostatectomy (RRP) radiotherapy (RT) decision making. METHODS: The records of consecutive patients who underwent RRP, who were referred for consideration of RT, and for whom an RIS scan was obtained were reviewed. The RT decisions, with regard to (a) the decision to offer RT and (b) the general volume to be treated [prostate fossa (PF) only versus PF + pelvis (P)] before knowledge of the RIS findings were charted. The RIS findings, with regard to uptake in the PF, uptake in the P, or extrapelvic (EP) uptake were tabulated. Then, the RT treatment decisions based on the RIS knowledge were evaluated and compared with the pre-RIS RT treatment decisions. RESULTS: Of the 54 patients originally referred for post-RRP RT, the initial decision was to recommend RT to the PF only in 52 cases and to PF+P in 2 cases. The RIS findings were as follows: PF only, 43 patients; PF+P, 8 patients; PF+EP, 2 patients; PF+P+EP, 1 patient. After knowledge of these RIS results, the decision to offer RT was withdrawn in 4 of 54 patients (7.4%; P = 0.046). Furthermore, RIS changed the general treatment volume (PF only to PF+P) in 6 of 54 patients (11.1%; P = 0.015). In total, RIS altered the RT decision in 10 of 54 patients (18.5%; P = 0.0067). Three-year biochemical failure-free survival (with failure defined as 2 consecutive prostate-specific antigen [PSA] rises above 0.2 ng/mL after PSA nadir) was 78%; no patient, disease, or treatment factor reached statistical significance on univariate or multivariate analysis. CONCLUSION: RIS was found to influence post-RRP RT decision making for the identification of patients not likely to benefit from RT and for guiding general target volume definition.

Impact of radioimmunoscintigraphy on definition of clinical target volume for radiotherapy after prostatectomy.

UNLABELLED: The goal of this study was to evaluate the role of radioimmunoscintigraphy (RIS) directed against prostate-specific membrane antigen in modifying postprostatectomy prostate fossa clinical target volume (CTV) definition. METHODS: The records of 25 postprostatectomy patients who received external-beam radiotherapy after prostatectomy and who underwent vessel-based RIS/planning CT registration were reviewed. For each patient, the CTV that would have been treated (CTV(pre)) before this registration was compared with that defined after the registration (CTV(post)). In addition, using a standard dose of 66 Gy in 2-Gy fractions, the corresponding bladder and rectum dose volume histograms were compared using 2 endpoints: volume receiving > or =60 Gy (V60) and area under the curve (AUC). RESULTS: The mean CTV(pre) vs. CTV(post) volumes were 24.4 vs. 35.0 cm(3), respectively (P = 0.032). The V60 results for CTV(pre) and CTV(post) were 32.7 vs. 41.0 cm(3), respectively, for the rectum (P = 0.168) and 33.9 vs. 46.6 cm(3), respectively, for the bladder (P = 0.015). The AUC results for CTV(pre) and CTV(post) were 4,027 vs. 4,516 Gy x cm(3), respectively, for the rectum (P = 0.396) and 4,782 vs. 5,561, respectively, for the bladder (P = 0.119). No Radiation Therapy Oncology Group grade 3, 4, or 5 (acute or late, gastrointestinal, or genitourinary) toxicity was observed. Two-year biochemical failure-free survival (with failure defined as 2 consecutive prostate-specific antigen rises above 0.2ng/mL) was 87% for the cohort. CONCLUSION: Incorporating RIS uptake resulted in significant modifications in CTV definition. The consequences of these modifications on the rectum V60 or AUC or on the bladder AUC were not significant, although the bladder V60 did increase. However, observed toxicity was low, with acceptable short-term biochemical control, suggesting that treatment to the modified CTV was tolerable.

Labeling anti-HER2/neu monoclonal antibodies with 111In and 90Y using a bifunctional DTPA chelating agent.

The goal of this investigation was to develop stable radioimmunoconjugates (RICs) of anti-HER2/neu monoclonal antibodies (MoAbs) for imaging and therapy in an animal model bearing human breast tumor xenografts that express normal (MCF-7 cells) and increased amounts of HER2/neu receptors (HCC-1954, BT-474, SKBR-3 cells) on their cell surface membranes. Pharmacy-grade Herceptin, a murine anti-HER2/neu MoAb, and nonspecific mouse IgG protein were conjugated with the recently developed DTPA linker known as CHX-A"-DTPA. These immunoconjugates were labeled with (111)InCl(3) and (90)YCl(3). Using a molar excess of 10:1 CHX-A"-DTPA to immunoglobulin, average specific activities of 1.87 microCi (111)In/microg RIC and 2.71 microCi (90)Y/microg RIC were obtained. The purity of RICs was 96%+ for (111)In and 99%+ for (90)Y. Stability in human plasma at 37 degrees C for both RICs ranged from 98% at 24 h to 85% at 96 h. Binding capacity of the RICs was tested with human cancer cell lines MCF-7, HCC-1954, BT-474, and SKBR-3. Using (111)In-labeled nonspecific IgG protein as a control, (111)In-Herceptin RIC was found to bind to MCF-7 cells with a ratio of 2.5:1 and to SKBR-3 cells with a ratio of 85:1 after 3 h of incubation. (111)In anti-HER2/neu RIC bound to MCF-7 cells with a ratio of 6:1 and to SKBR-3 cells with a ratio of 115:1 after 3 h of incubation. (90)Y-anti-HER2/neu RIC bound 10-times greater to BT-474 cells than to MCF-7 cells. Thus, these MoAbs can be labeled with (111)In and (90)Y using the CHX-A"-DTPA linker. The resulting RICs ((111)In- and (90)Y-anti HER2/neu antibodies) are stable and bind significantly to HER2 overexpressing tumor cell lines.

VIP grafted sterically stabilized liposomes for targeted imaging of breast cancer: in vivo studies.

Targeted delivery of radionuclides and therapeutic agents to specific biomarkers of breast cancer has important implications for the diagnosis and therapy of breast cancer. Vasoactive intestinal peptide receptors (VIP-R) are approximately five times more expressed in human breast cancer, compared to normal breast tissue. We have used VIP, a 28 amino acid mammalian neuropeptide, as a breast cancer targeting moiety for targeted imaging of breast cancer. VIP was covalently attached to the surface of sterically stabilized liposomes (SSL) that encapsulated a radionuclide, Tc99m-HMPAO. Rats with n-methyl nitrosourea (MNU)-induced in situ breast cancers were used to test this targeted liposomal imaging agent. Specifically, the pharmacokinetics and biodistribution of Tc99m-HMPAO encapsulating SSL with and without VIP were determined together with their ability to image breast cancer. The presence of VIP did not alter the size and Tc99m-HMPAO encapsulation ability of SSL. It also did not alter the pharmacokinetic profile of SSL. Long-circulating liposomes with and without VIP on their surface accumulated at significantly higher quantities in breast cancer when compared to normal breast, indicating passive targeting of these constructs to cancer tissues. Importantly, in breast cancer, Tc99m-HMPAO encapsulating SSL with VIP showed significantly more accumulation than SSL without VIP. The tumor to non-tumor ratio was also significantly higher for Tc99m-HMPAO encapsulating VIP-SSL than Tc99m-HMPAO encapsulating SSL without VIP, suggesting active targeting of VIP-SSL to breast cancer. Collectively, these data showed that Tc99m-HMPAO encapsulating VIP-SSL can be successfully used for the targeted imaging of breast cancer.