A much misunderstood caduceus and the case for an aesculapion.
Explore the source record for details and available documents.
Emblems and Insignia↗
Biomedical subjects
R Finn
Publications and source records attributed to R Finn.
Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography.
We report a series of studies that assess the feasibility and sensitivity of imaging of herpes virus type one thymidine kinase (HSV1-tk) gene transfer and expression with [124I]-5-iodo-2'-fluoro-1-beta-D-arabinofuranosyluracil ([124I]-FIAU) and positron emission tomography (PET) and the ability of [124I]-FIAU-PET imaging to discriminate different levels of HSV1-tk gene expression. Studies were performed in rats bearing multiple s.c. tumors derived from W256 rat carcinoma and RG2 rat glioma cells. In the first set, we tested the sensitivity of [124I]-FIAU-PET imaging to detect low levels of HSV1-tk gene expression after retroviral-mediated gene transfer. HSV1-tk gene transduction of one of preestablished wild-type W256 tumor in each animal was accomplished by direct intratumoral injection of retroviral vector-producer cells (W256-->W256TK* tumors). Tumors produced from W256 and W256TK+ cells served as the negative and positive control in each animal. Highly specific images of [124I]-FIAU-derived radioactivity were obtained in W256TK* tumors (that were transduced in vivo) and in W256TK+ tumors but not in nontransduced wild-type W256 tumors. The level of "specific" incorporated radioactivity in transduced portions of both W256TK* and W256TK+ tumors was relatively constant between 4 and 50 h. In the second set, we tested whether [124I]-FIAU and PET imaging can measure and discriminate between different levels of HSV1-tk gene expression. Multiple s.c. tumors were produced from wild-type RG2 cells and stably transduced RG2TK cell lines that express different levels of HSV1-tk. A highly significant relationship between the level of [124I]-FIAU accumulation [% injected dose/g and incorporation constant (Ki)] and an independent measure of HSV1-tk expression (sensitivity of the transduced tumor cells to ganciclovir, IC50) was demonstrated, and the slope of this relationship was defined as a sensitivity index. We have demonstrated for the first time that highly specific noninvasive images of HSV1-tk expression in experimental animal tumors can be obtained using radiolabeled 2'-fluoro-nucleoside [124I]-FIAU and a clinical PET system. The ability to image the location (distribution) of gene expression and the level of expression over time provides new and useful information for monitoring clinical gene therapy protocols in the future.
Animals↗
Tumor growth modulation by sense and antisense vascular endothelial growth factor gene expression: effects on angiogenesis, vascular permeability, blood volume, blood flow, fluorodeoxyglucose uptake, and proliferation of human melanoma intracerebral xenografts.
Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, has been investigated as a potent mediator of brain tumor angiogenesis and tumor growth. We evaluated the effect of VEGF expression on the pathophysiology of tumor growth in the brain. Human SK-MEL-2 melanoma cells, with minimal VEGF expression, were stably transfected with either sense or antisense mouse VEGF cDNA and used to produce intracerebral xenografts. Vascular permeability, blood volume, blood flow, and tumor fluorodeoxyglucose metabolism were assessed using tissue sampling and quantitative autoradiography. Tumor proliferation was assessed by measuring bromodeoxyuridine labeling indices. Tumor vascular density and morphological status of the blood-brain barrier were evaluated by immunohistochemistry. SK-MEL-2 cells transfected with sense VEGF (V+) expressed large amounts of mouse and human VEGF protein; V+ cells formed well-vascularized, rapidly growing tumors with minimal tumor necrosis. V+ tumors had substantial and significant increases in blood volume, blood flow, vascular permeability, and fluorodeoxyglucose metabolism compared to wild-type and/or V- (antisense VEGF) tumors. VEGF antisense transfected V- expressed no detectable VEGF protein and formed minimally vascularized tumors. V- tumors had a very low initial growth rate with central necrosis; blood volume, blood flow, vascular permeability, and glucose metabolism levels were low compared to wild-type and V+ tumors. A substantial inhibition of intracerebral tumor growth, as well as a decrease in tumor vascularity, blood flow, and vascular permeability may be achieved by down-regulation of endogenous VEGF expression in tumor tissue. VEGF-targeted antiangiogenic gene therapy could be an effective component of a combined strategy to treat VEGF-producing brain tumors.
Animals↗
Anti-G(D2) antibody treatment of minimal residual stage 4 neuroblastoma diagnosed at more than 1 year of age.
PURPOSE: To eradicate minimal residual disease with anti-G(D2) monoclonal antibody 3F8 in stage 4 neuroblastoma (NB) diagnosed at more than 1 year of age. PATIENTS AND METHODS: Thirty-four patients were treated with 3F8 at the end of chemotherapy. Most had either bone marrow (n=31) or distant bony metastases (n=29). Thirteen patients were treated at second or subsequent remission (group I) and 12 patients in this group had a history of progressive/persistent disease after bone marrow transplantation (BMT); 21 patients were treated in first remission following N6 chemotherapy (group II). RESULTS: Before 3F8 treatment, 23 patients were in complete remission CR, eight in very good partial remission (VGPR), one in partial remission (PR), and two had microscopic foci in marrow. Twenty-five had evidence of NB by at least one measurement of occult/minimal tumor (iodine 131[(131)I]-3F8 imaging, marrow immunocytology, or marrow reverse-transcriptase polymerase chain reaction [RT-PCR]). Acute self-limited toxicities of 3F8 treatment were severe pain, fever, urticaria, and reversible decreases in blood counts and serum complement levels. There was evidence of response by immunocytology (six of nine), by GAGE RT-PCR (seven of 12), and by (131)I-3F8 scans (six of six). Fourteen patients are alive and 13 (age 1.8 to 7.4 years at diagnosis) are progression-free (40 to 130 months from the initiation of 3F8 treatment) without further systemic therapy, none with late neurologic complications. A transient anti-mouse response or the completion of four 3F8 cycles was associated with significantly better survival. CONCLUSION: Despite high-risk nature of stage 4 NB, long-term remission without autologous (A)BMT can be achieved with 3F8 treatment. Its side effects were short-lived and manageable. The potential benefits of 3F8 in consolidating remission warrant further investigations.
Antibodies, Monoclonal↗
Interferon-gamma and monoclonal antibody 131I-labeled CC49: outcomes in patients with androgen-independent prostate cancer.
To assess the tumor targeting, safety, and efficacy of monoclonal antibody 131I-labeled CC49 in patients with androgen-independent prostate cancer, 16 patients received 75 mCi/m2 of the radiolabeled antibody after 7 days of IFN-gamma pretreatment. Sequential tumor biopsies in three patients showed a median 5-fold (range, 2-6-fold) increase in the proportion of cells staining positively for the TAG-72 antigen, whereas one showed a decrease in staining. Fourteen patients received 131I-labeled CC49, whereas 2 showed a disease-related decrease in performance status, precluding antibody treatment. The antibody localized to sites of metastatic androgen-independent prostate cancer in 86% (12 of 14; 95% confidence interval, 57-95%) of cases. Both osseous and extraosseous sites were visualized, and in six (42%) patients, more areas were visible when the radioimmunoconjugate was used than were apparent when conventional scanning techniques were used. The localization of the conjugate in the marrow cavity was usually a site not visualized by the radionuclide bone scan, in which the isotope localizes primarily to the tumor-bone interface. The dose-limiting toxicity was thrombocytopenia because five (36%) patients showed grade IV and seven (50%) showed grade III effects. In addition, six (42%) patients, four of whom were hospitalized, showed a flare in baseline pain, and four showed a decrease in pain. No patient showed a >50% decline in prostate-specific antigen, although radionuclide bone scans remained stable in four cases for a median of 4 months. The results are consistent with dosimetry estimates showing that the delivered dose to tumor was subtherapeutic and suggest that approaches that exclusively target the bone tumor interface or the marrow stroma may be unable to completely eradicate disease in the marrow cavity. For CC49, improving outcomes would require repetitive dosing, which was precluded by the rapid development of a human antimouse antibody response.
Aged↗
Segmentation of lung lesion volume by adaptive positron emission tomography image thresholding.
BACKGROUND: It is common protocol in radionuclide therapies to administer a tracer dose of a radiopharmaceutical, determine its lesion uptake and biodistribution by gamma imaging, and then use this information to determine the most effective therapeutic dose. This treatment planning approach can be used to quantitate accurately the activity and volume of lesions and organs with positron emission tomography (PET). In this article, the authors focus on the specification of appropriate volumes of interest (VoI) using PET in association with computed tomography (CT). METHODS: The authors have developed an automatic image segmentation schema to determine the VoI of metastases to the lung from PET images, under conditions of variable background activity. An elliptical Jaszczak phantom containing a set of spheres with volumes ranging from 0.4 to 5.5 mL was filled with F-18 activity (2-3 microCi/mL) corresponding to activities clinically observed in lung lesions. Images were acquired with a cold background and then with variable source-to-background (S/B) ratios of: 7.4, 5.5, 3.1, and 2.8. Lesion VoI analysis was performed on 10 patients with 17 primary or metastatic lung lesions, applying the optimum threshold values derived from the phantom experiments. Initial volume estimates for lung lesions were determined from CT images. Approximate S/B ratios were obtained for the corresponding lesions on F-18-fluoro-2-deoxy-D-glucose (18FDG)-PET images. From the CT estimate of the lesion size and the PET estimate of the S/B ratio, the appropriate optimum threshold could be chosen. The threshold was applied to the PET images to obtain lesion activity and a final estimate of the lesion volume. RESULTS: Phantom data analysis showed that image segmentation converged to a fixed threshold value (from 36% to 44%) for sphere volumes larger than 4 mL, with the exact value depending on the S/B ratios. For patients, the use of optimum threshold schema demonstrated a good correlation (r = 0.999) between the initial volume from CT and the final volume derived from the 18FDG-PET scan (P < 0.02). The mean difference for those volumes was 8.4%. CONCLUSIONS: The adaptive thresholding method applied to PET scans enables the definition of tumor VoI, which hopefully leads to accurate tumor dosimetry. This method can also be applied to small lesions (<4 mL). It should enable physicians to track objectively changes in disease status that could otherwise be obscured by the uncertainties in the region-of-interest drawing, even when the scans are delineated by the same physician.
Aged↗
Pharmacokinetics and acute toxicology of intraventricular 131 I-monoclonal antibody targeting disialoganglioside in non-human primates.
Tumors metastatic to the leptomeninges are often incurable despite current aggressive treatment modalities. Regional therapy by intrathecal administration of monoclonal antibodies (MoAbs) can maximize their concentration to tumor sites while reducing systemic toxicities. Anti-GD2 antibody 3F8 has successfully targeted human neuroectoderm derived tumors. Disialoganglioside GD2 expression in the central nervous system is identical between humans and cynomolgus monkeys. We studied the pharmacokinetics and the acute and subacute toxicities of intraventricular 131I-3F8 in 8 cynomolgus monkeys. Four animals were purposely immunized with intravenous 3F8 administered 2-4 weeks prior to injections. All animals remained clinically stable. Toxicities included weight loss, fever and CSF leukocytosis. One animal developed a left-sided hemiparesis following his seventh injection, presumably due to a local drug accumulation in the setting of an intermittently patent catheter. The estimated radiation dose to the CSF was 19-48 Gy in the immunized monkeys and 19-82 Gy in the nonimmunized monkeys, and to blood was 0.11-0.98 Gy and 0.29-2.03 Gy, respectively. Histopathology revealed chronic reactive changes adjacent to the region of catheter placement and a focal vasculitis in 2 animals. Peripheral blood counts and bone marrow examinations remained normal. Because of the blood-brain barrier, CSF monkey-anti-mouse antibody titers were less than 10 per cent of those in the serum. In contrast to the CSF radioactivity clearance which was similar in all animals, blood clearance was substantially accelerated in 3F8-immunized animals versus controls. Correspondingly, the CSF to blood dose ratio was improved 1.3 to 6.6 fold (mean 3.5). We conclude that intraventricular administration of 131I-3F8 in primates is tolerable. It can deliver very high doses of radiation to the CSF space with minimal toxicity to blood and bone marrow. Serum anti-mouse antibody accelerates the clearance of 131I-3F8 in blood and may improve the therapeutic index.
Animals↗
Imaging experimental brain tumors with 1-aminocyclopentane carboxylic acid and alpha-aminoisobutyric acid: comparison to fluorodeoxyglucose and diethylenetriaminepentaacetic acid in morphologically defined tumor regions.
The goal of this study was to evaluate the differences and define the advantages of imaging experimental brain tumors in rats with two nonmetabolized amino acids, 1-aminocyclopentane carboxylic (ACPC) acid and alpha-aminoisobutyric (AIB) acid compared with imaging with fluorodeoxyglucose (FDG) or the gallium-diethylenetriaminepentaacetic acid chelate (Ga-DTPA). 1-aminocyclopentane carboxylic acid, AIB, and FDG autoradiograms were obtained 60 minutes after intravenous injection to simulate positron emission tomography (PET) imaging, whereas the Ga-DTPA autoradiograms were obtained 5 or 10 minutes after injection to simulate gadolinium (Gd)-DTPA-enhanced magnetic resonance (MR) images. Three experimental tumors were studied (C6, RG2, and Walker 256) to provide a range of tumor types. Triple-label quantitative autoradiography was performed, and parametric images of the apparent distribution volume (Va, mL/g) for ACPC or AIB, relative glucose metabolism (R, micromol/100 g/min), vascular permeability to Ga-DTPA (K1, microL/min/g), and histology were obtained from the same tissue section. The four images were registered in an image array processor, and regions of interest in tumor and contralateral brain were defined on morphologic criteria (histology) and were transferred to the autoradiographic images. A comparative analysis of all measured values was performed. The location and morphologic characteristics of the tumor had an effect on the images and measurements of Va, R, and K1. Meningeal extensions of all three tumors consistently had the highest amino acid uptake (Va) and vascular permeability (K1) values, and subcortical portions of the tumors usually had the lowest values. Va and R (FDG) values generally were higher in tumor regions with high-cell density and lower in regions with low-cell density. Tumor areas identified as "impending" necrosis on morphologic criteria consistently had high R values, but little or no change in Va or K1. Tumor necrosis was seen consistently only in the larger Walker 256 tumors; low values of R and Va for AIB (less for ACPC) were measured in the necrotic-appearing regions, whereas K1 was not different from the mean tumor value. The highest correlations were observed between vascular permeability (K1 for Ga-DTPA) and Va for AIB in all three tumors; little or no correlation between vascular permeability and R was observed. The advantages of ACPC and AIB imaging were most convincingly demonstrated in C6 gliomas and in Walker 256 tumors. 1-aminocyclopentane was substantially better than FDG or Ga-DTPA for identifying tumor infiltration of adjacent brain tissue beyond the macroscopic border of the tumor; ACPC also may be useful for identifying low-grade tumors with an intact blood-brain barrier. Contrast-enhancing regions of the tumors were visualized more clearly with AIB than with FDG or Ga-DTPA; viable and necrotic-appearing tumor regions could be distinguished more readily with AIB than with FDG. [11C]-labeled ACPC and AIB are likely to have similar advantages for imaging human brain tumors with PET.
Aminoisobutyric Acids↗
Noninvasive imaging of herpes virus thymidine kinase gene transfer and expression: a potential method for monitoring clinical gene therapy.
Noninvasive imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression is possible with a clinical gamma camera and by single-photon emission tomography (SPECT) using 131I-labeled 2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil (FIAU). Studies were performed in rats bearing s.c. tumors. Tumors were produced by injection of wild-type RG2 glioma or W256 mammary carcinoma cells into one flank and RG2TK+ glioma or W256TK+ mammary carcinoma cells (that had been transduced in vitro with the HSV1-tk gene) into the opposite flank. In some animals, HSV1-tk gene transduction of the pre-established wild-type tumors was accomplished in vivo by direct intratumoral injection of retroviral vector-producer cells. Imaging studies were performed 2 weeks after tumor transduction to allow time for production and spread of the retroviruses through the tumor and for sufficient growth and increase in size of the tumors to facilitate imaging. The gamma camera and SPECT images revealed highly specific localization of [131I]FIAU-derived radioactivity to areas of HSV1-tk gene expression at 24, 36, and 48 h after i.v. administration of 1.6-2.8 mCi of [131I]FIAU. Comparative analysis of quantitative autoradiographic images obtained from the same tumors confirmed that the high levels of [131I]FIAU-derived radioactivity (> 1% dose) were localized to areas of HSV1-tk gene expression demonstrated by immunohistochemical staining for HSV1-tk protein. In contrast, significantly lower levels of [131I]FIAU-derived radioactivity (< 0.01%) were observed in the surrounding nontransduced tumor tissue, contralateral wild-type tumors, and other tissues that showed no immunohistochemical staining for the HSV1-tk protein. The magnitude of FIAU accumulation in RG2TK+, W256TK+, and wild-type tumors corresponded to the in vitro ganciclovir sensitivity of the cell lines used to produce these tumors, which indicates that the magnitude of FIAU accumulation reflects the level of HSV1-tk gene expression. We suggest that "clinically relevant" levels of HSV1-tk gene expression in transfected tissue can be imaged with [131I]FIAU and a gamma camera or SPECT, and that a significant improvement in imaging sensitivity and resolution is expected with [124I]FIAU and PET.
Animals↗
Pilot clinical trial of 5-[125I]iodo-2'-deoxyuridine in the treatment of colorectal cancer metastatic to the liver.
UNLABELLED: The thymidine analog, 5-iodo-2'-deoxyuridine (IUdR), is incorporated in the DNA of cells in the S phase. When incorporated into DNA, short-range Auger electrons emitted by 125I-labeled IUdR can cause double-strand breaks, delivering a lethal radiation dose to the cell. We conducted therapeutic trial to evaluate[125I/131I]IUdR pharmacokinetics in liver metastases from colorectal cancer. Dosimetry, safety, and therapeutic potential were assessed. METHODS: Four patients were each infused with 5 mCi [125I]IUdR and 10 mCi [131I]IUdR through the sideport of a hepatic artery pump. Iodine-131 images were quantitated and used for pharmacokinetic studies. The radioactivity in the DNA of biopsy samples of tumor, normal liver and bone marrow, obtained 24 or 48 hr after injection, was counted. RESULTS: All patients had [125I]IUdR and [131I]IUdR uptake in tumor, with a biexponential clearance. Repeat injections in individual patients showed little variation in tumor uptake, especially in the slow clearance component. On planar images, no long-term retention was seen in bone marrow or other actively dividing normal tissues. Radioactivity in all tumor DNA samples was greater than background, while that in normal liver cell DNA was at background levels. Radioactivity in the DNA of one marrow sample taken at 24 hr was above background, but in another taken at 48 hr it was equal to background levels. No side effects were noted, no hematologic toxicity was observed in any patients and no tumor responses were seen. CONCLUSION: There is persistent uptake of [125I]IUdR in hepatic tumors, thereby making hepatic artery infusion a suitable mode of delivery for therapy. Repeat injections will be needed because only 15%-50% of tumor cells are in the S phase. Based on results from this pilot study, a therapeutic regimen is being planned.
Adult↗
Pharmacokinetics and dosimetry of iodine-125-IUdR in the treatment of colorectal cancer metastatic to liver.
UNLABELLED: The radiotoxicity of 125I is highly sensitive to the site of decay relative to nuclear DNA. This paper describes a new approach, based upon pharmacokinetic clearance of radioactivity from the tumor, with which to quantify the fraction of [125I]IUdR incorporated within the DNA of tumor cells. METHODS: Patients were injected with [125I]IUdR through the hepatic artery. Iodine-131-IUdR was used as a tracer for imaging and quantitation. Both conventional and DNA-level dosimetry were performed. RESULTS: We calculated that if 15% of the tumor cells were in S phase at the time of injection, there would be 250 decays of 125I in the DNA per tumor cell after an infusion of 5 mCi [125I]IUdR. According to in vitro data based on 5 x 10(8) cells per g tumor, 99% of these cells in S phase would be killed. CONCLUSION: The estimate of cell inactivation is strongly dependent on the number of cells per gram and the fraction of cells in S phase at the time of injection, which indicates that repeat injections would be necessary to achieve a therapeutic effect.
Bone Marrow↗
Quantitative studies of monoclonal antibody targeting to disialoganglioside GD2 in human brain tumors.
Iodine-131 3F8, a murine IgG3 monoclonal antibody that targets to GD2-bearing tumors, was administered intravenously to 12 patients with brain tumors. Six patients received 2 mCi (0.74 Bq) of 131I-3F8, five patients 10 mCi (3.7 Bq)/1.73 m2 of 131I-3F8, and one patient 2.6 mCi (0.96 Bq) of 124I-3F8, with no side-effects. Nine of 11 malignant gliomas and the single metastatic melanoma showed antibody localization, with the best tumor delineation on single-photon emission tomography (SPET) following 10 mCi (3.7 Bq)/1.73 m2 dose. No nonspecific uptake in the normal craniospinal axis was detected. There was no difference in the pharmacokinetics of low-dose versus the higher-dose antibody groups; plasma and total-body half-lives were 18 h and 49 h, respectively. Surgical sampling and time-activity curves based on quantitative imaging showed peak uptake in high-grade glioma at 39 h, with a half-life of 62 h. Tumor uptake at time of surgery averaged 3.5 x 10(-3) %ID/g and peak activity by the conjugate view method averaged 9.2 x 10(-3) %ID/g (3.5-17.8). Mean radiation absorption dose was 3.9 rad per mCi injected (range 0.7-9.6) or 10.5 cGy/Bq (range 1.9-26). There was agreement on positive sites when immunoscintigraphy was compared with technetium-99m glucoheptonate/diethylene triamine penta-acetic acid planar imaging, thallium-201 SPET, and fluorine-18 fluorodeoxyglucose positron emission tomography. Taken together, these data suggest that quantitative estimates of antibody targeting to intracranial tumors can be made using the modified conjugate view method.
Adolescent↗
Case report: the diagnostic value of contrast-enhanced computed tomography in acute bilateral renal cortical necrosis.
Acute bilateral renal cortical necrosis is a relatively rare cause of acute renal failure accounting for only 2% of cases in the Western World. The pathophysiology of this condition is complex, but ultimately leads to the destruction of the renal cortex with sparing of the renal medulla. A definitive diagnosis is based on renal histology. In this report we describe a patient in whom this diagnosis was made using contrast-enhanced computed tomography as renal biopsy was contraindicated.
Acute Kidney Injury↗
The relationship between chronic drug ingestion and multiple myeloma.
Explore the source record for details and available documents.
Drug-Related Side Effects and Adverse Reactions↗
Food intolerance.
Explore the source record for details and available documents.
Food Hypersensitivity↗
Food intolerance.
Explore the source record for details and available documents.
Food Hypersensitivity↗
Phase I dose-escalation trial of iodine 131-labeled monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma.
PURPOSE: Eighteen patients with recurrent or refractory CD21-positive, non-Hodgkin's lymphoma (NHL) were treated in a phase IA dose-escalation therapeutic trial of iodine 131 labeled to a fixed dose of OKB7. METHODS: Individual doses of 30 to 50 mCi of 131I on 25 mg OKB7 were administered 2 to 3 days apart to achieve four total 131I-OKB7 dose levels of 90, 120, 160, and 200 mCi. Pharmacology, dosimetry, therapeutic effects, toxicity, human anti-mouse antibody (HAMA) response, and maximum-tolerated dose (MTD) were determined. Patients were evaluated by imaging studies (including whole-body gamma camera or single-photon emission computed tomography [SPECT] scans), flow cytometric analysis, bone marrow biopsy, and serial blood sampling. RESULTS: Median plasma and whole-body half-lives (T1/2) were 16 hours and 14 hours, respectively. Plasma and whole-body radiation doses were 0.0081 Gy/mCi and 0.0022 Gy/mCi, respectively. Specific tumor visualization was noted in eight of 18 patients. HAMA was detected in 12 of 16 patients. Nonhematologic toxicity was limited to asymptomatic elevations of thyroid-stimulating hormone (TSH) in five of 15 patients. Hematologic toxicity was observed in six of 18 patients, but was severe in only two patients. MTD in patients with diffuse lymphomatous bone marrow involvement was determined to be 200 mCi in four divided doses of 50 mCi 131I/25 mg OKB7. Antitumor activity was observed in 13 of 18 patients (one partial response [PR] and 12 mixed responses) and was dependent on the 131I-OKB7 dose administered. In general, palpable peripheral lymphadenopathy, enlarged spleens, skin lesions, and circulating OKB7-positive peripheral lymphocytes responded most readily to treatment. 131I-OKB7 was safely administered to a patient in leukemic phase of NHL with prompt subsequent loss of approximately 1 kg of tumor cells from the peripheral blood without associated tumor lysis syndrome. CONCLUSION: Because antitumor activity with tolerable toxicity was observed in the majority of this group of heavily pretreated patients, phase II investigation of mAb OKB7 radioconjugates in the therapy of NHL is warranted.
Adult↗
Iododeoxyuridine uptake and retention as a measure of tumor growth.
Iodine-131-iododeoxyuridine (IUdR) uptake and retention was measured in two C6 glioma cell lines (C6m and C6a) with different growth characteristics. Animals with intracerebral (i.c.) C6a tumors had a mean survival of 16 days, whereas only 1 of 20 animals with i.c. C6m tumors died during an 8-wk period of observation. The growth of i.c. C6m tumors could be described by the Gompertz equation; tumor doubling time increased from 1.9 to 5.2 days between Days 8 and 16 after tumor inoculation. Corresponding measurements of 131I-IUdR uptake and retention (24 hr after IUdR administration) by i.c. C6m tumors were also time-dependent and decreased from 0.075 to 0.027 to 0.011 %dose/g in 8-, 10- and 16-day-old tumors, respectively. Iodine-131-IUdR uptake in "rapidly growing" i.c. C6a tumors was substantially higher (0.30 %dose/g at 24 hr) than that in "slowly growing" i.c. C6m tumors and corresponded with differences in the survival data. Subcutaneous C6a tumors had comparable high uptake values (0.49 %dose/g at 24 hr), and 93% of total tumor radioactivity was recovered in DNA 24 hr after IUdR administration. Clearance of radioactivity was rapid in nonproliferative tissues; more than 80% of plasma radioactivity was cleared in 24 hr. Tumor-to-cortex radioactivity ratios ranged from 100/1 to 120/1 and 150/1 between 24, 48 and 96 hr after IUdR injection respectively. A "washout strategy," which reduces tissue background activity and increases specificity for PET and SPECT imaging of IUdR-DNA incorporation, is possible with longer-lived radioisotopes of iodine.
Animals↗