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Biomedical subjects

Michael J Blend

Publications and source records attributed to Michael J Blend.

9 recordsLinked to original sources
PubMed2006

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.

Humans↗
PubMed2004

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.

Humans↗
PubMed2004

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.

Aged↗
PubMed2004

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.

Cohort Studies↗
PubMed2003

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.

Animals↗
PubMed2003

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.

Antibodies, Monoclonal↗