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J A Coderre

Publications and source records attributed to J A Coderre.

At least 73 records · Page 4Linked to original sources
PubMed1994

Pinhole SPECT: an approach to in vivo high resolution SPECT imaging in small laboratory animals.

UNLABELLED: The performance of pinhole SPECT and the application of this technology to investigate the localization properties of radiopharmaceuticals in vivo in small laboratory animals are presented. METHODS: System sensitivity and spatial resolution measurements of a rotating scintillation camera system are made for a low-energy pinhole collimator equipped with 1.0-, 2.0- and 3.3-mm aperture pinhole inserts. The spatial detail offered by pinhole SPECT for in vivo imaging was investigated in studies of the brain and heart in Fisher 344 rats by administering 201TICI, 99mTc-HMPAO, 99mTc-DTPA and 99mTc-MIBI. Image acquisition is performed using a rotating scintillation camera equipped with a pinhole collimator; projection data are acquired in conventional step-and-shoot mode as the camera is rotated 360 degrees around the subject. Pinhole SPECT images are reconstructed using a modified cone-beam algorithm developed from a two-dimensional fanbeam filtered backprojection algorithm. RESULTS: The reconstructed transaxial resolution of 2.8 mm FWHM and system sensitivity of 0.086 c/s/kBq with the 2.0-mm pinhole collimator aperture provide excellent spatial detail and adequate sensitivity for imaging the regional uptake of the radiopharmaceuticals in tumor, organs and other tissues in small laboratory animals. CONCLUSION: The resolution properties of pinhole SPECT are superior to those which have been achieved thus far with conventional SPECT or PET imaging technologies. Pinhole SPECT provides an important approach for investigating localization properties of radiopharmaceuticals in vivo.

Animals↗
PubMed1993

Derivations of relative biological effectiveness for the high-let radiations produced during boron neutron capture irradiations of the 9L rat gliosarcoma in vitro and in vivo.

PURPOSE: Relative biological effectiveness (RBE) values for the high linear-energy-transfer particles produced during boron neutron capture therapy have generally been based on theoretical considerations or in vitro experiments. The purpose of this study was to independently determine RBE values for all of the boron neutron capture therapy dose components. METHODS AND MATERIALS: Clonogenic cell survival data were obtained for 9L rat gliosarcoma cells irradiated in the Brookhaven Medical Research Reactor thermal neutron beam both in vitro and as an intracerebral tumor. These data were analyzed using the linear quadratic model for cell survival to derive measured RBE values for all beam components and for a number of different boron compounds. RESULTS: In the absence of boron, the combined effects of the protons from the nitrogen capture, 14N(n,p)14C, and the fast neutron scatter, 1H(n,n')p, reactions generated RBEs of 3.7 in vitro and 3.2 in an in vivo/in vitro excision assay, compared to 250 kVp X rays using an end point of 1% cell survival. Apparent RBEs for the 10B(n,alpha)7Li reaction products were calculated from cell survival data following reactor irradiations in the presence of the amino acid p-boronophenylalanine, the sulfhydryl dodecaborate monomer or dimer, or boric acid. Apparent RBEs for the 10B(n,alpha)7Li reaction ranged from 1.2 to 9.8 depending on which boron compound was used. RBEs from the in vitro studies were consistently higher than from the in vivo/in vitro studies. Under any conditions, the apparent RBE for the 10B(n,alpha)7Li reaction with p-boronophenylalanine was higher than that with any other boron compound tested. CONCLUSIONS: Generally accepted RBE values for the fast neutron and 14N(n,p)14C reaction components of the total dose are too low. The apparent RBEs calculated for the 10B(n,alpha)7Li reaction were compound-dependent and consistent with differences in the distribution of 10B relative to glioma cell nuclei.

Animals↗
PubMed1993

Boron neutron capture therapy of intracerebral melanoma using boronophenylalanine as a capture agent.

A rat brain tumor model has been developed utilizing nude rats and the human melanoma cell line MRA 27. For pharmacokinetic and tissue distribution studies, 2 10(5) MRA 27 cells were implanted intracerebrally (i.c.), and 30 days later, 120 mg of 10B-enriched L-boronophenylalanine were injected i.p. into nude rats. 10B concentrations in the tumor, blood, and normal brain were 23.7, 9.4, and 8.4 micrograms/g, respectively, 6 h following administration. For therapy experiments, tumor bearing rats were irradiated at the Brookhaven Medical Research Reactor 30 days following implantation. The median survival time was 44 days for untreated rats, 76 days for those receiving a physical dose of 2.7 Gy, and 93 days for those receiving 3.6 Gy. Animals receiving both 10B-L-boronophenylalanine and physical doses of 1.8, 2.7, or 3.6 Gy (total tumor physical doses of 5.0, 7.5, or 10.1 Gy) had median survival times of 170, 182, and 262 days, respectively. Forty % of rats that received the highest tumor dose (10.1 Gy) survived > 300 days. In a replicate experiment 21% of animals that had received L-boronophenylalanine and irradiation (total tumor physical dose of 10.1 Gy) were alive 220 days after therapy. In a parallel study, animals that were irradiated with gamma photons from a 137Cs source with 12 Gy or 2.0 Gy 9 delivered to the head had median survival times of 86 and 79 days, respectively, compared to 47 days for untreated animals. Our results indicate that boron neutron capture therapy is effective against i.c. melanoma in a rodent model and suggest that large animal studies are warranted to further assess its efficacy.

Animals↗
PubMed1992

Identification of estrogen receptor mRNA and the estrogen modulation of parathyroid hormone-stimulated cyclic AMP accumulation in opossum kidney cells.

The opossum kidney (OK) cell was used as a model to test the hypothesis that estrogen directly affects proximal renal tubular epithelial cells. To demonstrate the expression of estrogen receptor in OK cells, we developed an approach using reverse transcription and the polymerase chain reaction. Analysis of the DNA amplified with nested primers revealed the predicted size fragment and restriction enzyme digestion products. To demonstrate the functional effects of estrogen, OK cells at confluence were preincubated in serum-free medium for 7-10 days with or without 17 beta-estradiol. Bovine PTH(1-34) (bPTH(1-34)) then stimulated a dose-dependent intracellular accumulation of cAMP that was maximal after 1 min and then gradually declined. Cyclic AMP in the medium slowly increased over 60 min. Preincubation with 17 beta-estradiol did not affect cell proliferation as measured by total protein content but caused an inhibition of bPTH(1-34)-stimulated intracellular cAMP accumulation that was maximal at 10(-11) M 17 beta-estradiol (71 +/- 3% control, p less than .001). bPTH(1-34) also increased cAMP release into the medium, an effect maximal using 10(-10) M 17 beta-estradiol (118 +/- 3% control, p less than .001). Preincubation with the inactive isomer 17 alpha-estradiol caused no changes in cAMP accumulation or release. Coincubation with the antiestrogen tamoxifen blocked the effects of 17 beta-estradiol. Sodium-dependent phosphate transport was: (1) inhibited by 2-h incubations with 10(-8) or 10(-10) M bPTH(1-34) and not affected by preincubation with 17 beta-estradiol, and (2) not inhibited by a 20-min incubation with 10(-8) M bPTH(1-34) unless cells were preincubated with 10(-8) M 17 beta-estradiol, suggesting that any possible effects of estrogen on phosphate transport are not directly mediated by changes in cAMP. These studies demonstrate the presence of estrogen receptor mRNA in OK cells as well as direct and specific effects of physiologic concentrations of estrogen on cAMP accumulation in these cells. This system may be a good model for further study of estrogen and PTH effects on the kidney.

Aged↗
PubMed1992

Control of intracerebral gliosarcomas in rats by boron neutron capture therapy with p-boronophenylalanine.

Boron neutron capture therapy (BNCT) of transplanted intracerebral GS-9L rat gliosarcomas was effected by irradiation at a nuclear reactor, primarily with thermal neutrons, after two intragastric doses of p-boronophenylalanine (BPA). At the time of BNCT, tumor 10B levels were approximately 40 micrograms 10B/g with tumor:blood and tumor:brain 10B concentration ratios of about 3.3:1 and 3.9:1, respectively. This resulted in calculated doses to tumor that were approximately 2.3-fold greater than those to normal brain parenchyma and brain vascular endothelium within the treatment volume. Approximately 75% of the tumor dose resulted from the 10B(n,alpha)7Li nuclear reaction. The median survival of untreated rats (n = 20) was 20 days after initiation of tumors. Reactor irradiation only (no BPA) increased the median survival to 25 days (n = 25). None of the rats in the untreated or irradiation-only groups survived longer than 34 days after initiation of tumors. Two BNCT dose levels were used: 8.9 Gy (19.3 Gy x relative biological effectiveness, or Gy-eq) and 13.4 Gy (29.0 Gy-eq). The median post-BNCT survivals of BPA-treated rats in the 8.9-Gy (n = 16) and 13.4-Gy (n = 12) groups were 60 and 120 days, respectively, including seven long-term (greater than 12 months) survivors at 8.9 Gy and six long-term (greater than 5 months) survivors at 13.4 Gy. Survival times following BPA-based BNCT (either 8.9 or 13.4 Gy) were significantly longer than those following 250-kVp X-ray doses of 15 Gy (n = 24), 22.5 Gy (n = 32) or 30 Gy (n = 26).

Animals↗
PubMed1991

Boron neutron capture therapy of a murine melanoma with p-boronophenylalanine: dose-response analysis using a morbidity index.

Boron-10 concentrations of 20 or 40 micrograms/g were attained in mouse B16 melanomas following one or two intragastric doses of p-boronophenylalanine (750 mg/kg body weight per dose), respectively. Tumor-to-normal-tissue (blood, muscle) boron concentration ratios were 4:1-6:1. The efficacy of boron neutron capture irradiation was monitored using the Wilcoxon two-sample test in conjunction with a system of ranking outcomes of different therapies that compared living mice and mice sacrificed because of excessive tumor growth concomitantly. Median survivals were extended progressively as radiation doses were increased up to 38.7 gray-equivalent (gray X relative biological effectiveness), with one of five and one of six tumors cured in each of the two highest dose groups, respectively. When comparable tumor inhibitory doses of 250-kVp X rays were used to treat these tumors, instead of the transient erythema and edema that resulted from boron neutron capture therapy, there resulted irreversible muscle necrosis in the irradiated zone and atrophy of the foot distal to the irradiated zone. The improvement in treatment outcome with boron neutron capture therapy is attributable to unprecedented tumor-to-normal-tissue radiation dose ratios of approximately 2.8 to 3.6.

Animals↗
PubMed1990

Selective delivery of boron by the melanin precursor analogue p-boronophenylalanine to tumors other than melanoma.

The melanin precursor analogue p-boronophenylalanine (BPA) has been used to deliver 10B to melanoma tissue for boron neuron capture therapy. Uptake studies in tumor models other than melanoma now indicate that BPA is capable of delivering therapeutic amounts of boron to tumors other than melanoma. The KHJJ murine mammary tumor carried s.c. in BALB/c mice, the GS-9L rat glioma carried both s.c. and intracranially in F-344 rats, and the human U-87 MG glioma xenograft carried s.c. in nude mice have all shown significant accumulation of boron in tumor tissue following single p.o. (intragastric) doses of BPA. In this KHJJ mammary tumor, the L isomer of BPA was preferentially accumulated compared to the D isomer, indicative of a carrier-mediated transport process. Double-label, whole-body autoradiographic studies in a pigmented murine melanoma have shown that the boron distribution (from BPA) differs from the distribution of a tritiated melanin precursor (tyrosine). Boron accumulated only in the tumor; labeled tyrosine accumulated in tumor, liver, intestinal epithelium, bone-marrow, and secretory glands. Toxicity studies in mice and rabbits indicate that, even at very high doses, BPA p.o. caused no adverse effect in tissues, on blood chemistry, or on differential leukocyte counts. These data indicate that BPA may be generally useful as a boron delivery agent for boron neutron capture therapy of tumors.

Animals↗
PubMed1990

Experimental boron neutron capture therapy for melanoma: systemic delivery of boron to melanotic and amelanotic melanoma.

The boron-containing melanin precursor analogue p-boronophenylalanine (BPA) has previously been shown to selectively deliver boron to pigmented murine melanomas when administered in a single intragastric dose. If boron neutron capture therapy is to become a clinically useful method of radiation therapy for human malignant melanoma, the boron carrier must be capable of delivering useful amounts of boron to remote tumor sites (metastases) and to poorly pigmented melanomas. We have now determined the ability of BPA to accumulate in several nonpigmented melanoma models including human melanoma xenografts in nude mice. The absolute amount of boron in the nonpigmented melanomas was about 50% of that observed in the pigmented counterparts but was still selectively concentrated in the tumor relative to normal tissues in amounts sufficient for effective neutron capture therapy. Single intragastric doses of BPA resulted in selective localization of boron in the amelanotic Greene melanoma carried in the anterior chamber of the rabbit eye and in a pigmented murine melanoma growing in the lungs. The ratio of the boron concentration in these tumors to the boron concentration in the immediately adjacent normal tissue was in the range of 3:1 to 4:1. These distribution studies support the proposal that boron neutron capture therapy may be useful as a regional therapy for malignant melanoma.

Animals↗
PubMed1989

Calcitonin inhibits accumulation of cyclic AMP in stimulated peritoneal macrophages from normal rats but not from osteopetrotic (incisors-absent) littermates.

Macrophages and osteoclasts derive from related cell lines. In osteopetrotic mutants the function of osteoclasts is greatly reduced compared to that in normal animals or children and macrophage function is variably affected depending upon the mutation. To further explore macrophage function in osteopetrosis we examined the regulation of cyclic AMP production in macrophages from mutants and normal littermates of the osteopetrotic stock incisors-absent (ia) in the rat. Surface stimulation by latex particles of elicited peritoneal macrophages from normal or osteopetrotic (ia) mutant rats caused an identical increase in the accumulation of cyclic AMP. This effect was inhibited in normal animals by coincubation of macrophages with calcitonin (CT) but this inhibition was either absent or less marked in macrophages from mutant littermates. In contrast to human monocytes preincubation of rat macrophages with pertussis toxin did not relieve this inhibition. This implies that rat peritoneal macrophages respond to CT by a different mechanism. These results demonstrate altered macrophage function in osteopetrotic animals and may be functionally related to the reduced CT binding previously described in ia osteoclasts. Furthermore, the coexistence of reduced function of macrophages and osteoclasts in the ia mutation suggests that macrophages and osteoclasts share a common progenitor.

Animals↗
PubMed1989

Therapeutic effects of S-35-thiouracil in BALB/c mice carrying Harding-Passey melanoma.

Thiouracil (TU) selectively binds to the pigment melanin during melanogenesis and is rapidly cleared from normal tissues. This compound shows little affinity for pre-formed melanin. BALB/c mice, carrying the subcutaneously transplanted Harding-Passey melanoma, were given i.p. injections of 35S-labeled thiouracil in a range of doses and administration schedules. Injected doses ranged from 1.3 to 10 mCi per mouse with resultant tumor dose rates of 10 to 30 cGy/hr, respectively. At the lower dose rates, growth delay of approximately 1 to 2 weeks was observed in all tumors. At the highest doses used, complete tumor regression (no regrowth) was observed in some cases, with extended growth delays of approximately 6 weeks in the rest. These results illustrate the possible utility of radiolabeled thiouracil as a systemically administered brachytherapy agent for melanoma.

Animals↗
PubMed1989

Direct electrophilic iodination of 2-thiouracil using Iodo-Gen.

5-Iodo-2-thiouracil (ITU) is of interest due to its ability to bind specifically to the pigment melanin during melanogenesis and is of potential value in the diagnosis and treatment of malignant melanoma. Radioiodinated ITU was prepared directly from 2-thiouracil in a two-phase reaction using Iodo-Gen in 0.05 M phosphate buffer pH 7.0. The identity radiochemical purity and stability of the product were checked by reversed-phase high pressure liquid chromatography (HPLC). ITU labeled with 123I, 125I or 131I has been produced in millicurie amounts and isolated on a semi-preparative reversed-phase HPLC column. Production time was 2-3 h, overall radiochemical yields averaged 80%; the radiochemical purity was greater than 98%. Specific activities on the order of 20 Ci/mmol have been obtained.

Animals↗
PubMed1989

Effects of estrogen in vivo and in vitro on spontaneous interleukin-1 release by monocytes from postmenopausal women.

Estrogen (E) inhibits bone resorption, but the mechanism of this effect is unknown. Interleukin-1 (IL-1) stimulates bone resorption in vitro and may be produced in bone by mononuclear phagocytes. Recently, the spontaneous release of IL-1 from peripheral monocytes was found to reflect bone formation in a subset of patients with idiopathic osteoporosis. We suspected that the action of E on bone is mediated indirectly by its effect on monocyte IL-1 activity. Eleven normal postmenopausal women taking no medications were given conjugated E (0.625 mg daily) for 3-9 weeks. Supernatants from cultured peripheral monocytes were analyzed for IL-1 production by stimulation of a cloned murine helper T-cell line. IL-1 release was expressed as a percentage of maximum release corrected for monocyte number. IL-1 release before E treatment was 11.0 +/- 0.2% (+/- SE), it was 7.8 +/- 1.6% after E treatment (P = NS). IL-1 release fell in each of the three women with the highest initial values (46% to 5%, 25% to 17%, and 18% to 12%). IL-1 release did not correlate with serum osteocalcin or fasting urinary calcium either before or after E treatment. Addition of 10(-7)-10(-10) mol/L 17 beta-estradiol to cultured monocytes obtained before E treatment caused an increase in IL-1 release that did not follow a dose-response relationship. Treatment of postmenopausal women with E did not affect spontaneous IL-1 release by peripheral monocytes in vitro. The addition of E in vitro did not produce consistent changes in IL-1 release by these cells. This does not exclude the possibility that E may affect monocyte IL-1 release in subsets of women with high spontaneous monocyte IL-1 release with or without osteoporosis.

Adult↗
PubMed1989

Effects of estrogen on mineral metabolism in postmenopausal women as evaluated by multiple assays measuring parathyrin bioactivity.

Data on the effect of estrogen on immunoreactive parathyrin (iPTH) in postmenopausal women are conflicting. We administered estrogen or placebo to 21 postmenopausal women for 12 weeks and measured PTH bioactivity (bioPTH), using the renal cytochemical bioassay. Before treatment, there was a negative correlation between nephrogenous cAMP and the tubular maximum for urinary phosphate excretion and a positive correlation between values measured by a mid-region-specific PTH RIA and those measured in an immunoradiometric assay for intact PTH. Values measured by the midregion-specific RIA were also positively correlated with nephrogenous cAMP. BioPTH values were not correlated with other indices of PTH activity but were increased compared with values for younger subjects. After estrogen treatment there was no change in bioPTH activity despite an early decrease in serum osteocalcin and a later increase in nephrogenous cAMP. PTH concentrations measured by mid-region-specific or intact RIAs were unchanged, but sample size may have been insufficient to exclude the possibility of significant changes in these values. The effects of estrogen on mineral metabolism in postmenopausal women are time-dependent. Early effects are independent of PTH, and later effects are variably associated with increased PTH activity.

Adult↗
PubMed1988

Boron neutron capture therapy of a murine melanoma.

Boron neutron capture therapy has been carried out on BALB/c mice carrying the Harding-Passey melanoma s.c. on the thigh. p-Boronophenylalanine (BPA), a boronated analogue of natural melanin precursors, was used to target boron selectively to melanoma. BPA was administered to the mice either via i.p. injection or p.o. by intubation. 10B concentrations in tumor ranged from 15 to 40 ppm depending on the route and timing of administration. Irradiations with a predominantly thermal neutron beam were performed at the Brookhaven Medical Research Reactor. In the absence of BPA, only transient tumor growth delays were observed at low neutron fluences. At 5 x 10(16) n/m2, 4 of 22 tumors irradiated in the absence of BPA underwent long-term tumor growth control; after p.o. administration of BPA (40 ppm 10B in the tumor), the fraction of tumors controlled increased to 11 of 19. The average dose to the tumor in the latter group was 17.8 Gy, of which 14.8 Gy were due to the 10B neutron capture reaction. The biological effectiveness of the absorbed dose from the neutron capture reaction, at the 50% tumor control level, was found to be twice that of 100 kVp X-rays.

Animals↗