PubMed Health⌕ Search

Biomedical subjects

G H Hinkle

Publications and source records attributed to G H Hinkle.

At least 19 recordsLinked to original sources
PubMed1999

Immunoscintigraphy with indium-111-capromab pendetide: evaluation before definitive therapy in patients with prostate cancer.

OBJECTIVES: No standard noninvasive diagnostic test reliably differentiates patients with organ-confined prostate cancer from those with lymph node metastases. The ability of a radiolabeled monoclonal antibody, indium-111 (111ln)-capromab pendetide, to identify sites of metastatic disease in patients at moderate to high risk of nodal involvement was investigated. METHODS: The study prospectively evaluated 160 patients with prostate cancer scheduled to undergo pelvic lymph node dissection (PLND) before or during definitive treatment. All were at relatively high risk of nodal involvement by virtue of significantly elevated baseline prostate-specific antigen (PSA) values, Gleason scores, and/or locally advanced clinical stages of disease. The histologic findings of the PLNDs were compared with the results of immunoscintigraphy, computed tomography, and magnetic resonance imaging. RESULTS: Among the 152 evaluable patientS studied with 111In-capromab pendetide before PLND, the sensitivity of immunoscintigraphy for lymph node detection was 62% and the specificity was 72%; the positive predictive value was 62% and the negative predictive value was 72%. In comparison, the sensitivity of computed tomography and magnetic resonance imaging was 4% and 15%, respectively, and the specificity was 100% for both procedures on the basis of a large number of negative interpretations. Logistic regression analysis revealed that immunoscintigraphy with 111In-capromab pendetide provided strong, independent evidence of the presence of lymph node metastases. Furthermore, the analysis indicated that certain combinations of PSA, Gleason score, and 111In-capromab pendetide were particularly effective at predicting the risk of nodal involvement. CONCLUSIONS: Immunoscintigraphy with 111In-capromab pendetide outperformed standard diagnostic imaging techniques in the detection of prostate cancer lymph node metastases and provided independent prognostic information that complemented PSA, Gleason score, and clinical stage.

Adenocarcinoma↗
PubMed1999

99mTc-HYNIC-folate: a novel receptor-based targeted radiopharmaceutical for tumor imaging.

UNLABELLED: The folate receptor is overexpressed in a wide variety of human tumors. Conjugates of folate have been shown to be selectively taken up by tumor cells via the folate receptor. In this study, a novel radiopharmaceutical, 99mTc-6-hydrazinonicotinamido-hydrazido (HYNIC)-folate, was synthesized and evaluated for its efficacy as a targeted agent for the imaging of tumors that overexpress the folate receptor. METHODS: HYNIC-folate was synthesized and radiolabeled with 99mTc using tricine and trisodium triphenylphosphine-3,3',3"-trisulfonate as coligands. The receptor binding properties of 99mTc-HYNIC-folate were studied in cultured tumor cells that overexpress the folate receptor. The tumor-localizing properties of 99mTc-HYNIC-folate were then evaluated in C57BL/6 mice bearing subcutaneously implanted folate receptor-positive syngeneic tumors. Tissue distribution was determined at two different time points, and gamma camera images were collected on two animals. RESULTS: The folate receptor-mediated uptake of 99mTc-HYNIC-folate by cultured tumor cells was approximately 300 times higher than the nonspecific binding determined in the presence of 1 mmol/L free folic acid. Excellent tumor selectivity was also shown in the animal model; tumor-to-blood ratios reached 55+/-19 and 81+/-6 at 4 and 24 h after injection, respectively. Tumor uptake of the radiotracer was blocked by the co-injection of 100 microg free folate. Tumors were clearly identifiable on the gamma camera images, with the kidneys and the bladder as the only normal organs showing high levels of the radiotracer. CONCLUSION: 99mTc-HYNIC-folate is a promising, novel receptor-specific radiopharmaceutical with potential applications in the imaging of human tumors.

Animals↗
PubMed1999

Lymphoscintigraphy and intraoperative lymphatic mapping of sentinel lymph nodes in melanoma patients.

Identification of sentinel lymph nodes (SLNs) using lymphoscintigraphy, the blue dye technique and intraoperative lymphatic mapping with a gamma-detecting probe has become the standard of care in diagnosing and treating melanoma. Numerous clinical studies have proven the reliability of predicting the histology of remaining lymph nodes in the lymphatic basin from the histologic evaluation of the SLNs. Technical and clinical factors presented in this paper have been shown to increase the accuracy of localization of SLNs. The nuclear medicine technologist shares a vital role in the radiopharmaceutical preparation and administration for preoperative lymphoscintigraphy and intraoperative lymphatic mapping in patients with melanoma.

Humans↗
PubMed1998

Multicenter radioimmunoscintigraphic evaluation of patients with prostate carcinoma using indium-111 capromab pendetide.

BACKGROUND: Optimum therapy for prostate carcinoma patients requires accurate staging, but computed tomography (CT) and magnetic resonance imaging (MRI) have limitations as methods for detecting soft tissue metastases. In this study, radioimmunoscintigraphy (RIS) was evaluated for its ability to identify sites of metastatic disease in lymph nodes. METHODS: RIS was evaluated in 51 prostate carcinoma patients at high risk for metastatic disease. An intravenous infusion of indium-111 capromab pendetide was given, followed by nuclear medicine imaging on two separate dates. Bilateral, open pelvic lymph node dissection was performed with additional exploration and biopsy of scan positive extraprostatic regions. Histologic evaluation of removed tissue confirmed the accuracy of RIS. In addition, results were compared with other standard methods for diagnosing patients prior to surgery. RESULTS: Nineteen patients (37%) had evidence of lymph node involvement with RIS. Fifteen of the 19 positive patients had pathologic evidence of cancer in the biopsied lymph nodes. Sensitivity, specificity, accuracy, and the positive predictive value for detection of extraprostatic disease were 75%, 86%, 81%, and 79%, respectively. CT, MRI, and ultrasound of the pelvis demonstrated a combined accuracy of only 48% in detecting lymph node disease. Twenty-five previously undetected sites were deemed positive with RIS. Fourteen of these were biopsy-proven tumor sites, seven were probable tumor sites, and four were assumed to be false-positive. CONCLUSIONS: RIS had an impact on patient management through its detection of occult disease in more than 50% of prostate carcinoma patients studied, and it provided information concerning the likelihood that lymph node metastases would be found during surgery.

Antibodies, Monoclonal↗
PubMed1998

Prostate cancer abdominal metastases detected with indium-111 capromab pendetide.

To provide appropriate therapy for prostate cancer, accurate staging of the patient's disease is essential. Determination of tumor size, location, periprostatic extension and metastatic disease in the skeleton and soft tissue are needed to stage properly. Current diagnostic modalities may lead to understaging in 40%-70% of prostate cancer. Detection of metastatic disease, both at the time of initial diagnosis and in patients with suspected local recurrence, can significantly alter the type of therapy given. Clinical studies using the (111)In radiolabeled immunoconjugate, MAb 7E11-C5.3-GYK-DTPA (capromab pendetide), have shown the superiority of radioimmunoscintigraphy over other diagnostic modalities in the detection of both primary and metastatic prostate cancer. Radioimmunoscintigraphy with capromab pendetide depends on expression of tumor-associated antigen rather than lesion size. Earlier detection of extraprostatic invasion and metastases by means of radioimmunoscintigraphy provides valuable information for treatment decisions. A case of metastatic prostate cancer in the abdomen of a patient without local disease, in which the extent of disease was confirmed at autopsy after sudden cardiac arrest, is presented.

Abdominal Neoplasms↗
PubMed1997

Technical considerations for acquiring and processing indium-111 capromab pendetide images.

A diagnostic quality 111In capromab pendetide study depends on parameters such as the quality control of the camera, thorough patient preparation, adequate imaging time and accurate computer processing. Comparisons of different patient preparation methods, imaging times, and camera and processing parameters were evaluated to provide high-quality 111In capromab pendetide images and to develop acquisition and processing parameters for 111In capromab pendetide imaging. SPECT images provide the best views of metastatic pelvic nodal involvement. Volume rendered three-dimensional registration best differentiates between normal vasculature and metastatic disease. Optimal acquisition parameters for delayed imaging included 128 x 128 matrix and 65 sec/step. The LFOV dual-head SPECT camera required only one SPECT acquisition that encompassed both the pelvis and abdomen. Planar and SPECT positioning was critical in evaluating questionable lymph nodes. In processing these images, the most diagnostic results were obtained with a three-dimensional low-pass post filter. The most effective patient preparation consisted of an oral cathartic, enema and catheterization when needed.

Antibodies, Monoclonal↗
PubMed1996

Pharmacokinetics of iodine-125 CC49 monoclonal antibody in patients with colon cancer.

UNLABELLED: Radioimmunoguided Surgery techniques which use radiolabeled tumor specific markers and an intraoperative detector in an attempt to improve therapy and survival in patients with cancer have been under development for over fifteen years. Monoclonal antibody (MAb) CC49 is a second-generation murine IgG1 which has improved localization properties over its predecessor, MAb B72.3, and has been studied in a number of patients. In order to determine the pharmacokinetics of iodine-125 (125I) CC49 MAb, size-exclusion, high-performance liquid chromatography (HPLC) was used to assess radioactive components in serum and urine following administration of the drug to colon cancer patients. METHODS: Five patients received an intravenous infusion of 10 mg of MAb CC49 labeled with 2 mCi 125I. Following infusion, serum and urine specimens were collected from patients at predetermined time intervals prior to surgery. HPLC analysis of these specimens was completed to determine the radioactive species in each sample. RESULTS: Serum and urine specimens showed that serum levels of CC49 decrease exponentially and become unmeasurable by day 14 (half-life 1.89 days, +/- 0.19), with a steady, low-level of free 125I measurable in postinjection serum until day 21 after infusion. There was no evidence of MAb fragmentation or antibody:antigen (Ab:Ag) complex formation in serum, and no evidence of whole MAb, F(ab')2, or Fab fragment excretion in urine. Preinjection sera with MAb added in vitro also failed to demonstrate Ab:Ag complex formation. Analysis of urine showed low level excretion of free 125I which peaked by day 1 and declined exponentially through day 21, with a very low molecular weight (< 1 kDa) MAb fragment excreted in urine between 1 and 21 days. CONCLUSION: Radioiodinated 125I CC49 MAb remains in serum of cancer patients approximately 14 days, and tissue radioactivity beyond this time may reflect tissue sequestered MAb and/or free 125I and not "bloo pool" radioactivity. CC49 MAb appears to be deiodinated in small but significant quantities before it is metabolized, and clearance of radioactivity is mainly in free 125I form in urine. Measurable quantities of a < 1 Kda MAb fragment in urine and not serum may suggest a renal mechanism of MAb metabolism, but may also represent a metabolic end product of MAb metabolism with a very short serum half-life (T1/2) which accumulates in urine.

Aged↗
PubMed1995

Monoclonal antibody imaging of recurrent and metastatic prostate cancer.

In summary, this agent is safe for administration and more accurate than any currently available imaging modality for the detection of extraprostatic metastases. This agent is still under investigation and some day may aid urologists in the evaluation of prostate cancer by improving preoperative staging and demonstration of advanced disease and postoperative localization of recurrent disease. Improved staging and localization will reduce unnecessary tests and treatment that will lead to reduced morbidity, better management, earlier detection, and intervention in advanced disease and improved cost-effectiveness.

Aged↗
PubMed1993

Radioimmunoguided radical prostatectomy and lymphadenectomy.

BACKGROUND: The feasibility of using radioimmunoguided surgery (RIGS) (Neoprobe Corp., Columbus, OH) for intraoperative detection of prostate cancer was examined in a pre-Phase I clinical study involving 10 patients having radical prostatectomy and lymphadenectomy. METHODS: Patients were injected with iodine 125-radiolabeled B72.3 monoclonal antibody, which has been shown previously to bind to TAG-72, a pancarcinoma and oncofetal antigen. At a mean of 26 days after injection, RIGS was performed with a specially designed intraoperative gamma-detecting probe. RESULTS: By comparing probe counts with counts of appropriate background tissues, the RIGS system successfully localized tumor to the prostate of all 10 patients. Clinically occult and histologically confirmed bilateral intraprostatic tumor was identified in three patients. One additional patient had bilateral positive intraprostatic probe count ratios with the RIGS technique; on histologic examination, tumor was identified unilaterally, and extensive high-grade prostatic intraepithelial neoplasia was found on the contralateral side. Probe count ratios were positive in the lymph nodes of three patients; two had tumor confirmed histologically. CONCLUSIONS: The current investigation supports the feasibility of the RIGS technique and the need for additional studies.

Antibodies, Monoclonal↗
PubMed1993

Blood-brain barrier permeability and the brain extracellular space in acute cerebral inflammation.

The diffusion properties of the brain cortical extracellular space have never been examined in models of inflammation, even though inflammation can cause increased blood-brain barrier permeability. Uptake of intravascular 125I-labelled albumin and the diffusion of the tetramethylammonium ion within the brain extracellular space was measured in an experimental brain abscess to determine the effect of acute inflammation upon blood-brain barrier permeability and diffusion properties of the cortical extracellular space. The blood-brain transfer constant for albumin was increased in the abscess region, indicating that an increase in blood-brain barrier permeability occurred in animals inoculated with a weakly pathogenic strain of Staphylococcus aureus. The volume fraction of the extracellular space, as measured by the diffusion of tetramethylammonium ion, ranged from 0.19 to 0.23 in bacteria inoculated subjects and from 0.21 to 0.22 in controls. The tortuosity of the extracellular space ranged from 1.40 to 1.42 in bacteria inoculated subjects and was 1.39 in controls. These results showed that the volume fraction and tortuosity of the cortical extracellular space were not affected by inflammation even though vascular permeability was increased. This result was supported by the finding that brain water content, measured in the same animals, was increased to a non-significant extent in the bacteria inoculated subjects. These findings lead to the conclusion that acute inflammation induced by a weak pathogen can cause increased blood-brain barrier permeability without a significant change in the diffusion properties of the brain cortical space.

Animals↗
PubMed1993

Intraoperative localization of neuroendocrine tumors with 125I-TYR(3)-octreotide and a hand-held gamma-detecting probe.

BACKGROUND: This study evaluates a novel method of intraoperative localization of endocrine gastroenteropancreatic tumors with a hand-held gamma-detecting probe to detect in situ tumor binding of the radioiodinated somatostatin analog 125I-TYR(3)-octreotide. METHODS: Seven patients with biochemical and radiologic evidence of a specific endocrine tumor, one patient with biochemical evidence of gastrinoma but no tumor localized by conventional imaging techniques, and four patients with equivocal preoperative biochemical or radiologic study results but suspected of harboring a neuroendocrine tumor underwent abdominal exploration with intraoperative injection of 125I-TYR(3)-octreotide. 298 +/- 63 microCi. A hand-held gamma-detecting probe was used during operation to determine whether gross tumor accumulated the radiolabeled analog and occult tumor could be detected. Positive uptake was defined as tumor/background ratios exceeding 2:1. RESULTS: The tumor in all seven patients with gross disease accumulated 125I-TYR(3)-octreotide. Occult tumor beyond that appreciated with preoperative imaging or by routine operative exploration was detected in a patient with carcinoid tumor. In the patient with the occult gastrinoma the probe detected the lesion within the duodenal bulb before duodenotomy and also predicted what proved histologically to be positive peripancreatic adenopathy. There was a single false-positive reading from the stomach in a patient with suspected carcinoid tumor in whom no tumor could be found grossly or histologically. A pancreatic mass that probed negative proved to be an adenocarcinoma of ductal origin. CONCLUSIONS: Tumor-specific peptide-receptor binding can be detected in situ with 125J-TYR(3)-octreotide and a hand-held gamma-detecting probe. This technique may facilitate neuroendocrine tumor localization and operative cytoreduction.

Adult↗
PubMed1990

Alterations in monoclonal antibody affinity and antigenic receptor site expression on mycoplasma-infected human colorectal cancer cells.

The affinity of MoAb CO 17-1A and expression of its antigenic target were studied on uninfected and mycoplasma-infected colorectal cancer cell lines SW 1116 and SW 948. Binding of 125I-labeled CO 17-1A to SW 1116 cells was quantified at 37 degrees C by determination of the affinity constant (Ka) and the number of antigenic receptor sites (r) per cell using Scatchard plots. When mycoplasma-free SW 1116 cells were used as targets, Ka was 0.92 +/- 0.06 x 10(8) M-1 and r = 1.32 +/- 0.14 x 10(6) at 37 degrees C. One batch of unspeciated, mycoplasma-infected SW 116 cells had reduced affinity and a decreased number of antigenic receptor sites per cell for 125I-labeled 17-1A, while another batch of infected SW 1116 cells had a 4- to 5-fold increase in r and diminished Ka for the antibody compared with uninfected cells. When unspeciated, mycoplasma-infected SW 948 cells were exposed to 125I-labeled 17-1A and the data subjected to Scatchard analysis, the affinity of the antibody deviated markedly from linearity and rendered analysis for Ka and r meaningless. These data indicate that mycoplasma infection can produce variable effects on the cellular expression of antigenic receptor sites and the affinity of antibody for its target, and emphasize the importance of using mycoplasma-free cell lines in studies of these parameters.

Animals↗
PubMed1990

Quality control test for immunoreactivity of radiolabeled antibody.

A rapid method for the measurement of the immunoreactive fraction of a radiolabeled monoclonal antibody or antibody fragment has been developed. This may be used as a quality control test prior to patient administration of the radiolabeled antibody preparation. The test employs solid phase antigens and the assay is conducted under conditions of antigen excess. Assay parameters have been evaluated and a standardized procedure has been developed. The assay has been compared to a standard extrapolation method and found to give approximately the same result. The test has been used on four different radiolabeled antibodies currently in clinical trials in patients with colorectal cancer. Mean immunoreactive fractions for these radiolabeled antibodies ranged from 35 to 65% and the variability of the immunoreactive fraction ranged from 140 to 240% for different antibodies. We conclude that the quality, defined as the immunoreactive fraction, of radiolabeled antibodies is both low and highly variable, indicating the need for a quality control test of these radiopharmaceuticals in the clinic prior to patient administration.

Animals↗
PubMed1989

The use of a hand-held gamma detector improves the safety of isolated limb perfusion.

We used two hand-held gamma-detecting probes (GDP) (Neoprobe 1000 system) capable of detecting small gamma emissions to monitor leakage in patients undergoing hyperthermic isolated limb perfusion (HILP) who received 800 microCi Technetium 99m pentetate through the perfusate. The percentage of gamma-ray leakage was calculated by a simultaneous reading of two probes at 1-minute intervals (one over the precordial area and one over the thigh) and this was compared to results of simultaneous blood sampling from the perfusate and systemic circulation at 15-minute intervals for gamma well counting (GWC). The percentage of leakage recorded by the GDPs was essentially identical to that detected by the GWC (7.3% and 8.2%, respectively at the conclusion of the perfusion). The GDP gives an immediate and accurate indication of the percentage of leakage during HILP, making it a safer procedure.

Aged↗
PubMed1989

An assessment of prolonged reactivity of seven monoclonal antibodies against CX-1 tumor xenografts using a hand-held gamma-detecting probe.

The biodistribution and kinetics of 7 monoclonal antibodies (MAb) with known reactivity against CX-1 tumor were examined over 21 days using a hand-held gamma-detecting probe (Neoprobe system). Twenty-eight immuno-deprived (athymic) nude mice implanted with human colon adenocarcinoma CX-1 xenografts were injected intraperitoneally with 50 microCi of 125I-labeled antibodies (4 mice/antibody). Of the 7 monoclonal antibodies, 4 were anti-CEA (MA, MB, MC, and MD), 2 were anti-TAG 72 (B72.3 NCI and B72.3 fermented) and one was anti-colorectal cancer (17-1A). Daily probe counts were recorded in duplicate over the tumor site and the contralateral nontumor site (background), and tumor-to-background (Tu/Bkg) ratios were calculated. Animals were sacrificed on day 21, and blood, heart, liver, spleen, lungs, kidneys, intestine, muscle, and the tumor were removed for gamma well counting. All antibodies identified the tumor as early as 24 h postinjection and specific tumor localization improved over time. Patterns of prolonged tumor binding varied considerably from one antibody to another, although all but one (MB) showed continuously increasing Tu/Bkg ratios. These data indicate progressive clearance of the antibodies from the background tissue and a persistence of labeled MAb activity in tumor resulting in improved tumor localization with increasing postinjection time.

Adenocarcinoma↗
PubMed1988

Intraoperative radioimmunolocalization of colorectal carcinoma with a hand-held gamma probe and MAb B72.3: comparison of in vivo gamma probe counts with in vitro MAb radiolocalization.

A new intraoperative approach to tumor localization using radiolabelled monoclonal antibody (MAb) B72.3 involves the use of a hand-held gamma-detecting probe (GDP) by the surgeon and, subsequently, the pathologist. We report here the use of 125I-labelled MAb B72.3 IgG and a GDP to localize primary and metastatic colorectal cancer in 31 patients. The patients were administered radiolabelled MAb i.v., and all underwent surgical exploration 5 to 35 days post-injection. In vivo localization of the MAb was evaluated using a GDP, with tumor and normal tissue counts being obtained. In each case, the subsequent tumor and normal tissue that were resected were analyzed in vitro for MAb localization; this was evaluated by calculating the radiolocalization index, i.e., the ratio of the injected dose per gram localized to tumor versus that of normal tissue. When the GDP was used intraoperatively, MAb B72.3 localized tumors in 68% (21/31) of the patients; the arbitrary criterion of tumor-to-normal tissue ratios higher than or equal to 2.0:1 in vivo being taken as positive. Resected tumor radiolocalization indices ranged from 0.5 to 543, and 71% (22/31) of the patients studied had tumors with radiolocalization indices higher than or equal to 3. Of 50 carcinoma biopsies, 34 that were probe-positive were antigen-positive when B72.3 was used in immunoperoxidase assays, while 4 carcinoma biopsies that were probe-negative were also antigen-negative. Twelve of 50 biopsies were probe-negative and antigen-positive, but many of these lesions only contained a few antigen-positive cells; none of the 50 was probe-positive and antigen-negative. Tumors of all histologic grades localized injected MAb and, in general, higher in vivo probe ratios and radiolocalization indices were obtained from patients who underwent surgery 20 to 35 days following injection of the MAb. MAb B72.3 localized tumor in all sites to which colon carcinoma commonly metastasizes, including mesenteric and peri-aortic lymph nodes, liver, lung, and peri-rectal soft tissue. There was a strong statistical correlation (p = 0.001) between detecting MAb B72.3 localization to tumors using the GDP intraoperatively and subsequent in vitro analysis of cpm/g for tumor versus normal tissues. These studies thus further validate the use of 125I-labelled MAb B72.3 IgG and of a hand-held gamma probe for the intraoperative detection of carcinomatous lesions.

Adult↗