Radiation dosimetry results and safety correlations from 90Y-ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory non-Hodgkin's lymphoma: combined data from 4 clinical trials.

Ibritumomab tiuxetan is an anti-CD20 murine IgG1 kappa monoclonal antibody (ibritumomab) conjugated to the linker-chelator tiuxetan, which securely chelates (111)In for imaging or dosimetry and (90)Y for radioimmunotherapy (RIT). Dosimetry and pharmacokinetic data from 4 clinical trials of (90)Y-ibritumomab tiuxetan RIT for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) were combined and assessed for correlations with toxicity data. METHODS: Data from 179 patients were available for analysis. Common eligibility criteria included <25% bone marrow involvement by NHL, no prior myeloablative therapy, and no prior RIT. The baseline platelet count was required to be > or = 100,000 cells/mm(3) for the reduced (90)Y-ibritumomab tiuxetan administered dose (7.4-11 MBq/kg [0.2-0.3 mCi/kg]) or > or = 150,000 cells/mm(3) for the standard (90)Y-ibritumomab tiuxetan administered dose (15 MBq/kg [0.4 mCi/kg]). Patients were given a tracer administered dose of 185 MBq (5 mCi) (111)In-ibritumomab tiuxetan on day 0, evaluated with dosimetry, and then a therapeutic administered dose of 7.4-15 MBq/kg (0.2-0.4 mCi/kg) (90)Y-ibritumomab tiuxetan on day 7. Both ibritumomab tiuxetan administered doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve ibritumomab tiuxetan biodistribution. Residence times for (90)Y in blood and major organs were estimated from (111)In biodistribution, and the MIRDOSE3 computer software program was used, with modifications to account for patient-specific organ masses, to calculate radiation absorbed doses to organs and red marrow. RESULTS: Median radiation absorbed doses for (90)Y were 7.42 Gy to spleen, 4.50 Gy to liver, 2.11 Gy to lung, 0.23 Gy to kidney, 0.62 Gy (blood-derived method) and 0.97 Gy (sacral image-derived method) to red marrow, and 0.57 Gy to total body. The median effective blood half-life was 27 h, and the area under the curve (AUC) was 25 h. No patient failed to meet protocol-defined dosimetry safety criteria and all patients were eligible for treatment. Observed toxicity was primarily hematologic, transient, and reversible. Hematologic toxicity did not correlate with estimates of red marrow radiation absorbed dose, total-body radiation absorbed dose, blood effective half-life, or blood AUC. CONCLUSION: Relapsed or refractory NHL in patients with adequate bone marrow reserve and <25% bone marrow involvement by NHL can be treated safely with (90)Y-ibritumomab tiuxetan RIT on the basis of a fixed, weight-adjusted dosing schedule. Dosimetry and pharmacokinetic results do not correlate with toxicity.     

90Y-ibritumomab tiuxetan in the treatment of relapsed or refractory B-cell non-Hodgkin's lymphoma

OBJECTIVE: Non-Hodgkin's lymphoma (NHL) is the most frequently diagnosed malignancy of the immune system, with more than 53,900 new cases diagnosed in 2002. Conventional cancer therapies cure many, but not the majority of, cases of the aggressive forms of NHL, and the more indolent and follicular forms of the disease that affect nearly half of all patients with NHL are considered incurable. In the absence of cure or survival benefits, treatments such as radioimmunotherapy that induce remission and prolong time off therapy are considered valuable. (90)Y-Ibritumomab tiuxetan recently became the first radioimmunotherapy agent to be approved for commercial use by the U.S. Food and Drug Administration. After reading this article, the nuclear medicine technologist should be able to understand the incidence and prevalence of NHL, describe the ibritumomab tiuxetan therapy protocol, explain specific infusion techniques for this protocol, list acquisition parameters after injection of (111)In-ibritumomab tiuxetan, and describe specific safety techniques to keep risk as low as reasonably achievable while performing the therapy protocol.     

Diagnostic imaging prior to 90Y-ibritumomab tiuxetan (Zevalin) treatment in follicular non-Hodgkin's lymphoma

Add-on treatment of follicular non-Hodgkin's lymphoma (NHL) with yttrium-90 labelled ((90)Y) ibritumomab tiuxetan (Zevalin) has become an efficacious asset in standard treatment concepts of this disease. First-line treatment with Zevalin is currently under way. Whereas in the U.S. and Switzerland a prediagnostic imaging with (111)In-ibritumomab tiuxetan is mandatory, in Europe there is no such prerequisite. It is shown in this article why a prediagnostic imaging or dosimetry is not necessary as an additional mandatory safety measure to confirm the expected biodistribution.     

Biodistribution and kinetics of (131)I-labelled anti-CD20 MAB IDEC-C2B8 (rituximab) in relapsed non-Hodgkin's lymphoma

The native chimeric human-mouse anti-CD20 antibody IDEC-C2B8 (rituximab) is therapeutically applied in relapsed non-Hodgkin's lymphoma (NHL). The purpose of this study was to evaluate the distribution and pharmacokinetics of iodine-131 labelled rituximab in humans for radioimmunotherapy of relapsed CD20-positive NHL. Thirty-five patients with relapsed NHL were administered 20-40 mg rituximab labelled with 250 MBq (131)I. Biodistribution was determined by the gamma camera whole-body scans, whole-body probe measurements and the analysis of serial blood and urine samples. Dosimetry was performed using the MIRDOSE 3 program. Antibody administration was well tolerated. The whole-body activity showed a mono-exponential decrease with a wide range of effective half-lives, the mean value (88 h) being significantly longer than the half-life of its murine counterpart, tositumomab. This led to appropriately higher dose factors for the whole body and organs. Activity was excreted mainly through the kidneys. Normal organs showed decreasing ratios of organ to whole-body activity over time, whereas the tumour tissue presented different kinetics, with increasing ratios of tumour to whole-body activity as evidence for specific antibody binding. It is concluded that (131)I-labelled rituximab is suitable for pretherapeutic dosimetry. Due to the wide range of whole-body and organ dose factors, individual dosimetry is necessary for radioimmunotherapy with (131)I-labelled rituximab. The therapeutic activities of (131)I-labelled rituximab required to deliver similar doses should be lower than those of its murine counterpart.     

In-111 ibritumomab scintigraphy (planar and SPECT) and FDG PET/CT before Y-90 ibritumomab treatment in a patient with mantle cell lymphoma

We report the case of a 75-year-old man, in whom Y-90 ibritumomab was requested because of relapse of blastoid variant mantle cell lymphoma diagnosed in 1995. Before Y-90 ibritumomab treatment, FDG PET and In-111 ibritumomab scintigraphy with planar views at 24 hours, 48 hours, and 5 days, including SPECT, were performed. Discordant information between both examinations was observed as, in addition to the lesions detected by In-111 ibritumomab imaging, FDG PET detected lesions that did not take up the ibritumomab. The discrepancy shown by both radiotracers has to be kept in mind before planning treatment with Y-90 ibritumomab, and for the correct evaluation of treatment response.     

Perioperative high-dose-rate brachytherapy (PHDRB) in previously irradiated head and neck cancer: Initial results of a Phase I/II reirradiation study

BACKGROUND: This study was undertaken to determine the feasibility of salvage surgery and perioperative high-dose-rate brachytherapy (PHDRB) at the dose/fractionation schedule proposed in patients with previously irradiated, recurrent head and neck cancer or second primary tumors arising in a previously irradiated field. METHODS AND MATERIALS: Twenty-five patients were treated with surgical resection and PHDRB. The PHDRB dose was 4 Gy b.i.d. x 8 (32 Gy) for R0 resections and 4 Gy b.i.d. x 10 (40 Gy) for R1 resections. Further external beam radiotherapy or chemotherapy was not given. RESULTS: Resections were categorized as R0 (negative margins of at least 10 mm) in 3 patients (12.0%) and R1 (negative margins of less than 10 mm or microscopically positive margins) in 22 (88.0%). Twelve patients with R1 resections had microscopically positive margins (48%), and 10 patients had close margins (40%), with a median of 2.0 mm. Ten patients (40.0%) developed Radiation Therapy Oncology Group Grade 3 or greater toxicity. Seven patients (28%) presented complications requiring a major surgical procedure. Four of these complications appeared in the immediate postoperative period and were surgical in nature (flap failure, n = 2; fistula, n = 2), and the other three were mainly related to the brachytherapy procedure (n = 2) or the radiation dose delivered (n = 1). One patient died on postoperative day 11 due to bleeding. After a median followup of 14 months, the 4-year local control rate and overall survival were 85.6% and 46.4%, respectively. CONCLUSIONS: Surgical salvage and PHDRB at the dose/fractionation proposed are feasible in this high-risk population. Toxicity is high, but not substantially different from other reirradiation series. Four-year local control results are encouraging taking into account that 22 of 25 patients (88%) had either close or microscopically positive margins.     

A stylized computational model of the rat for organ dosimetry in support of preclinical evaluations of peptide receptor radionuclide therapy with (90)Y, (111)In, or (177)Lu.

The therapeutic effects of peptide receptor-based radionuclide therapy are extensively being investigated in rats bearing tumors. Both the dose to the tumor and the therapy-limiting dose to normal tissues, such as kidneys and bone marrow, are of interest for these preclinical studies. The aim of this work was to develop a generalized computational model for internal dosimetry in rats. METHODS: Mature rats were dissected and the relative positions, dimensions, and weights of all of their major organs were measured. A mathematic model was set up for the rat body and its internal organs to enable Monte Carlo radiation transport calculations to determine estimates for both tumor and organ self-doses as cross-organ doses for (90)Y, (111)In, and (177)Lu. The organs and body were mostly of ellipsoid shape with the axes given as the measured length, width, and height normalized to values that, together with the measured weights, are consistent with the recommended soft-tissue and bone densities. A spheric tumor of 0.25 g was positioned on the right femur. Calculations were performed with the Monte Carlo neutral particle transport code MCNP for the beta-emitters (maximum energy, 2.28 MeV) and (177)Lu (maximum energy, 0.497 MeV) and for the gamma-emissions from (177)Lu and from (111)In. The presented absorbed dose S values are used to calculate the absorbed dose estimates for the rat organs in a study on the biodistribution of (177)Lu-DOTA-Tyr(3)-octreotate (DOTA is 1,4,7,10-tetraazadodecane-N,N',N",N"'-tetraacetic acid). Three activity distributions were considered in the kidney: uniform in the whole kidney, in the cortex, or in the outer 1-mm-thick rim of the cortex. Isodose curves and dose volume histograms were calculated for the dose distribution to the kidneys. RESULTS: Depending on the activity distribution in the kidneys, the renal dose for (177)Lu-DOTA-Tyr(3)-octreotate is 0.13-0.17 mGy/MBq. CONCLUSION: The renal dose of 70-95 Gy for an injected activity of 555 MBq will likely cause radiation damage, although the higher amount of peptide with this activity may influence the dosimetry by partial receptor saturation. Dose volume histograms show that (111)In and (177)Lu are likely to have a higher threshold for renal damage than (90)Y.     

Mid-term results in otherwise treatment refractory primary or secondary liver confined tumours treated with selective internal radiation therapy (SIRT) using <Superscript>90</Superscript>Yttrium resin-microspheres

The purpose was to determine the response and survival and to analyse the feasibility of single-session, whole-liver SIRT in patients with non-resectable, otherwise non-responding liver cancer. Thirty-nine patients qualified for SIRT. Eighteen patients suffered from colorectal-cancer metastases (CRC), breast-cancer metastases (MBC, 7), HCC (5) and other tumours (9). Response was assessed by tumour-markers and CT-imaging. At 2-4, 5-7 and 8-9 months follow-up in 3/17, 5/15 and 5/10 of CRC-patients CEA-levels were higher than before. In the MBC group 1-3 and 4-6 months after SIRT tumour-marker-levels were higher in 2/6 and 3/3 patients, respectively. In all HCC-patients AFP-levels dropped 1-3 months after SIRT. Using RECIST, in the CRC-group progressive liver disease (PD) was found in 4/17, 2/12, 2/10 and 2/5 patients at 2-4, 5-8, 9-10 and 12-14 months follow-up. Concerning MBC, after 3 months 7/7 patients presented with stable-disease (SD) or partial-response (PR). At 5-6 months, 1/5 patients showed PD. All HCC-patients showed SD/PR at 2-3 months with no PD at 5-8 months. In the mixed-group 5/6 patients presented with SD/PR at 3-4 months and with SD in 2/3 patients at 5-6 months. The median time-to-PD was 6.5, 8.5 and 8 months for the CRC-, MBC- and mixed-group, respectively. SIRT is a promising, liver-targeted approach for patients with otherwise treatment-refractory liver tumours.     

Accelerated partial breast irradiation for suitable elderly women using a single fraction of multicatheter interstitial high-dose-rate brachytherapy: Early results of the Single-Fraction Elderly Breast Irradiation (SiFEBI) Phase I/II trial

Purpose/ObjectiveTo evaluate feasibility and early clinical outcomes of a single fraction of multi-catheter interstitial high-dose rate brachytherapy for accelerated partial breast irradiation (APBI) in the elderly.Material/MethodsFrom November 2012 to September 2014, 26 patients (≥70) with early breast cancer were enrolled in a prospective phase II trial (NCT01727011). After lumpectomy, intra-operative catheter implant was performed for post-operative APBI (single fraction 16 Gy). Surveillance was achieved at 1, 3 and 6 months after APBI, then twice a year. Acute toxicity was investigated. Early cosmetic outcome was analyzed (patient, radiation oncologist, 2 observers). Local and regional relapse-free survival, cancer specific survival and overall survival were analyzed.ResultsMedian age was 77 years [69–89]. Median CTV was 41 cc [22-95]. Acute toxicity was observed in 18 pts (70%) with a total of 44 events: G1: 75.7%; G2: 22.8%; G3: 4.5%. Breast fibrosis (31.8%), puncture site inflammation (13.6%) and skin hyperpigmentation (11.4%) were the most frequent side effects. Cosmetic evaluation at 6 months was excellent/good in 88%, 92%, 85% and 88% for patient, radiation oncologist, observer #1 and #2 respectively. With a median follow-up of 37.2 months [35.6-42.3], side effects were G1: 4 pts (15%) and G2: 1 pt (4%). Three-year Local and regional relapse-free survival, cancer specific survival and overall survival rates were 100%, 100%, 100% and 95.2% respectively.ConclusionsFor elderly early breast cancer, a post-operative multi-catheter interstitial high-dose rate brachytherapy single dose (16 Gy) appears feasible. Acute toxicity is acceptable as well as early cosmetic outcome. Oncologic outcome seems encouraging and allows going forward with new clinical trials focusing on single fraction APBI.     

Biodistribution and therapeutic efficacy of (125/131)I-, (186)Re-, (88/90)Y-, or (177)Lu-labeled monoclonal antibody MN-14 to carcinoembryonic antigen in mice with small peritoneal metastases of colorectal origin.

Therapeutic efficacy in radioimmunotherapy depends, among other things, on the choice of the radionuclide. The aim of the present study was to determine the most suitable radionuclide for radioimmunotherapy with monoclonal antibody MN-14 to carcinoembryonic antigen in an experimental model of small peritoneal metastases of colorectal origin. METHODS: In nude mice with intraperitoneal LS174T tumors (diameter, 1-3 mm), the biodistributions of MN-14 labeled with (131)I ((131)I-MN-14), (186)Re-mercaptoacetyltriglycine ((186)Re-MN-14), and (88)Y-diethylenetriaminepentaacetic acid (DTPA) ((88)Y-MN-14) after intravenous and intraperitoneal administration were determined. Subsequently, the therapeutic efficacies of equally toxic activity doses of (131)I-MN-14 (9.25 MBq per mouse), (186)Re-MN-14 (9.25 MBq per mouse), (90)Y-MN-14 (3.15 MBq per mouse), and MN-14 labeled with (177)Lu-DTPA ((177)Lu-MN-14) (8.33 MBq per mouse) after intraperitoneal administration were determined. RESULTS: Each of the radioimmunoconjugates preferentially accumulated in tumor nodules, both after intravenous administration and after intraperitoneal administration. Values for clearance from blood were similar for all radioimmunoconjugates. The uptake of (88)Y-MN-14 in the liver and spleen was significantly higher than the uptake of (131)I-MN-14 or (186)Re-MN-14. Maximal uptake values (mean +/- SD) in tumors were 58 +/- 7 percentage injected dose per gram of tissue (%ID/g) for (131)I-MN-14 (24 h after administration), 83 +/- 19 %ID/g for (186)Re-MN-14 (72 h after administration), and 148 +/- 89 %ID/g for (88)Y-MN-14 (192 h after administration). Dosimetric analysis of the biodistribution data estimated that the radiation doses guided to the tumor by intraperitoneally administered (131)I-MN-14, (186)Re-MN-14, (90)Y-MN-14, and (177)Lu-MN-14 were 150, 100, 45, and 200 Gy, respectively. The median survival time of control mice, treated with unlabeled MN-14, was 42 d, whereas the median survival times of mice treated with (131)I-MN-14, (186)Re-MN-14, (90)Y-MN-14, and (177)Lu-MN-14 were 100 d (range, 58-142; P < 0.0001), 72 d (range, 46-84; P = 0.0002), 82 d (range, 46-142; P < 0.0001), and 136 d (range, 56-142; P < 0.0001), respectively. At the completion of the experiment (142 d after tumor cell inoculation), no residual disease was found in 8 of 9 long-term survivors ((131)I, n = 3; (90)Y, n = 1; and (177)Lu, n = 4). CONCLUSION: The uptake of (88)Y-MN-14 in small peritoneal LS174T xenografts was higher than the uptake of (131)I-MN-14 or (186)Re-MN-14. The present study indicates that (131)I and (177)Lu are the most suitable radionuclides for the radioimmunotherapy of small peritoneal metastases.     

Accelerated partial breast irradiation in the elderly: 5-Year results of the single fraction elderly breast irradiation (SiFEBI) phase I/II trial

PurposeTo evaluate the clinical outcomes of a very-accelerated partial breast irradiation (vAPBI) in the elderly based on a single fraction of multicatheter interstitial high-dose rate brachytherapy (MIB). Mature results with a median follow-up of 5 years.Methods and MaterialsFrom November 2012 to September 2014, 26 patients (pts) (≥70) with early breast cancer were enrolled in a prospective phase II trial (NCT01727011). After lumpectomy, intraoperative catheter implant was performed for postoperative APBI (single fraction 16 Gy). Surveillance was performed twice a year after APBI. Oncologic outcome (local [LRFS], metastasis-free survival, cancer-specific survival, and overall survival [OS]) as well as late toxicity and cosmetic outcome were investigated.ResultsMedian age was 77 years [69–89]. After a median follow-up of 63 months [60–68], 5-year LRFS, metastasis-free survival, cancer-specific survival, and overall survival rates were 100%, 95.5%, 100%, and 88.5%, respectively. Late toxicity was observed in 5 pts (19.2%) with a total of five events: 3 pts G1 (60%); and 2 pts G2 (40%). The observed late side effects were breast pain in 1 pt (G2 cytosteatonecrosis with occasional acetaminophen consumption), hypopigmentation (puncture site) in 2 pts (G1) and breast fibrosis in 2 pts (G1: 1 pt; G2: 1 pt). Cosmetic evaluation was excellent for 21 pts (81%) and good for 2 pts (19%).ConclusionFor elderly with early breast cancer, a vAPBI using a single fraction of postoperative MIB (16 Gy) provides excellent oncologic results, mainly in terms of local control and cancer death. Late toxicity and cosmetic profile are acceptable.     

Biodistribution, dosimetry and metabolism of 11beta-methoxy-(17alpha,20E/Z)-[123I]iodovinylestradiol in healthy women and breast cancer patients.

The biodistribution and dosimetry of the 20E and 20Z stereoisomers of 11 beta-methoxy-(17alpha,20)-[123I]iodovinylestradiol (MIVE) were evaluated in six healthy women. Tumor uptake and metabolism of the 20Z isomer were evaluated in 13 women referred after abnormal mammography or after discovery of a suspect mass at physical examination. METHODS: The radiopharmaceuticals were prepared from their corresponding stannyl intermediates and administrated intravenously. Blood samples were drawn at different time intervals and urine was collected for up to 24 h. Metabolites were detected by radiochromatography. Tissue distribution was followed for up to 24 h by scintigraphic imaging. The dosimetry was computed according to the Medical Internal Radiation Dose scheme. RESULTS: The 20E and 20Z isomers exhibit similar biodistribution and dosimetry patterns. Chromatographic analysis of plasma samples of healthy volunteers and cancer patients, as well as in vitro plasma incubations, confirmed the in vivo stability of (20Z)-[123I]MIVE. Radioactivity was rapidly cleared from the blood by the liver and excreted through the gut, which received the highest radiation dose (0.211 mGy/MBq). The effective doses for the adult female and male phantom were 0.054 and 0.046 mSv/MBq, respectively. Among the 13 patients imaged with (20Z)-[123I]MIVE, 3 had fibrocystic disease with no focal uptake, 8 had good agreement with in vitro estrogen receptor determination and 2 were false-positive. CONCLUSION: The radiation dose after intravenous administration of 20E- or (20Z)-[123I]MIVE at imaging dose levels is within acceptable limits. There was a good correlation between uptake of (20Z)-[123I]MIVE and the presence of estrogen receptors in breast cancer patients.     

Endoluminal angioplasty, in situ thrombolysis and arterial endoprosthesis. Immediate and long-term results (2 to 8 years): report of 5,216 operations

Over a period of 8 years, 5,216 percutaneous transluminal angioplasties (PTA) and local thrombolysis were performed in the Department of Radiology of the University of Freiburg and the Hochrheinklinik of Bad S?ckingen. From 1984 to 1989, 5,216 patients were reviewed clinically, and, in 360 cases, angiographically. The short-term results were compared with the long term results (i.e. 2 to 8 years after PTA or local lysis). The (stage IIb to stage IV) occlusive disease was treated by PTA. A successful PTA result was obtained in stage IIb in 73% of cases, in stage III in 68% of cases and, in stage IV in 36% of cases after 2-8 years including all regions of treated arteries. Complications occurred in 2.51% of cases. Over the last 2 years, dilatations, local thrombolysis and even intraluminal stent implantations can be controlled by ultrathin angioendoscopes.     

18F-FDG PET/CT联合改良国际预后指标(NCCN-IPI)对弥漫大B细胞淋巴瘤预后评估的价值分析

目的 探讨改良国际预后指标（NCCN-IPI）对治疗结束后18F-FDG PET/CT评价为阴性的弥漫大B细胞淋巴瘤（DLBCL）患者的预后分层价值。 方法 回顾性分析2013年4月至2017年8月在苏州大学附属第一医院经过6~8周期R-CHOP类方案化疗后,并经18F-FDG PET/CT评价为阴性的60例DLBCL患者的临床资料,其中男性28例、女性32例,中位年龄51岁（16~81岁）。采用NCCN-IPI进行危险度分层,采用 Log-rank 检验比较各组间无进展生存（PFS）期和总生存（OS）期的差异。 结果 所有患者2年PFS率为83.33%（50/60）,2年OS率为96.67%（58/60）。根据NCCN-IPI评分,低危组占35.0%（21/60）,低中危组占41.7%（25/60）,中高危组占18.3%（11/60）,高危组占5.0%（3/60）。低危组与其他组间PFS差异有统计学意义（P=0.0272、0.0143、<0.0001）,高危组与其他组间OS差异有统计学意义（P=0.0098、0.0166、0.0045）,余各组间PFS及OS差异无统计学意义（均P>0.05）。 结论 应用NCCN-IPI可以对治疗结束后18F-FDG PET/CT评价为阴性的DLBCL患者进行进一步的预后分层。     

Pharmacokinetics and brain distribution in non human primate of R(-)[123I]DOI,A 5HT(2A/2C) serotonin agonist

Our goal was to synthesize with high specific activity R(-)-1-(2,5-Dimethoxy-4-[123I]iodophenyl)-2-aminopropane [R(-)[123I]DOI], an in vitro potent and selective 5-HT(2A/2C) serotonin agonist, and study in vivo its plasma pharmacokinetics and brain distribution in baboon by SPECT. The purpose was to evaluate this radiotracer as a potential tool in discerning the role of the agonist high affinity state of 5-HT(2) receptors in depression and other neurological disorders.The radiotracer was prepared by electrophilic radioiodination of the N-trifluoroacetyl precursor of R(-)-1-(2,5-Dimethoxyphenyl)-2-aminopropane [R(-)DMA-TFA] with high-purity sodium [123I]iodide in the presence of chloramine-T, followed by amino deprotection with KOH in isopropanol (labeling yield: 73%, radiochemical yield: 62%, radiochemical purity: 99%). In vivo studies in baboon showed high accumulation of radioactivity in thalamus, the frontoparietal cortex, temporal, occipital and the striatum regions, with slightly lower accumulation in the midbrain and cerebellum. Ketanserin did not displaced the radioactivity in any of these brain regions. Plasma metabolite analysis was performed using methanol protein precipitation, the methanol fractions contained from 68% to 92% of the mixture of a labeled metabolite and parent compound. The recovery coefficient of unmetabolized R(-)[123I]DOI was 68%. The percent parent compound present in the extracted fraction, measured by HPLC, decreased gradually with time from 99.8% to 0.3% still present after 4.7 hours post injection whereas the percentage of the only one detected metabolite increased conversely. Free fraction determination (f(1)), was 31 +/- 0.9% (n = 3). For comparison purposes, ex-vivo brain distribution, displacement and metabolite analysis was also carried out in rodents. Although R(-)[123I]DOI displayed good brain uptake and localized in serotonergic areas of the brain, its target to non target ratio and its insensitivity to ketanserin displacement suggest high nonspecific uptake, therefore non potentially useful as brain imaging radiotracer for visualization of the agonist high-affinity state of 5-HT(2A) receptors and for visualizing 5-HT(2C) receptors by SPECT.     

Syntheses, in vitro and in vivo characterization of a 99mTc-(I)-tricarbonyl-benzylamino-dihydroxymethyl phosphine (NP(2)) chelate.

Studies were performed to study the complexation chemistry of 99mTc(CO)(+)(3) with a new tridentate amino-dihydroxymethyl phosphine (NP(2)) ligand with the 99mTc(CO)(3)(OH(2))(+)(3) synthon at tracer levels. A single, well-defined 99mTc(CO)(3)NP(2) complex is formed at pH 7.5 within 10 min at 60 degrees C that exhibits high in vitro and in vivo stability.     

Animal studies on the reduction and/or dilution of 2-deoxy-2-[18F]fluoro-d-glucose (FDG) activity in the urinary system

To evaluate two methods for decreasing and/or diluting the FDG activity in the urinary system, five rats were intraperitoneally given 1,000 μg/g ofl-lysine 4 times, starting from 60 minutes before iv injection of FDG, and then at 30-minute intervals for 90 minutes. Five rats were used as controls. In a furosemide study, 12 rats were allocated to three groups. Group 1 received iv injection of FDG alone. Group 2 received saline before iv injection of FDG. Group 3 received furosemide (7 mg/kg) and saline (1/30 of body weight). Neither renal uptake nor urinary excretion of FDG had a statistically significant difference: renal uptake; 0.179 ± 0.011 (l-lysine) vs. 0.119 ± 0.003 (control) % kg injected dose/g. The % dose excreted and total urine volume were: 15.0 ± 2.5 to 15.5 ± 2.5 with 2.98 ml (l-lysine), 22.9 ± 1.8 to 24.2 ± 1.5 with 1.41ml (control). The furosemide study revealed a statistically significant difference: Group 1; 7.57 ± 4.73, Group 2; 0.686 ± 0.638, Group 3; 2.37 ± 2.33% kg injected dose/g (p < 0.01 for Group 1 vs. Group 2, p < 0.05 for Group 1 vs. Group 3). While pretreatment withl-lysine or furosemide failed to decrease renal activity of FDG, saline injection without furosemide markedly decreased urinary activity.