Biomedical subjects

F F Knapp

Publications and source records attributed to F F Knapp.

At least 55 records · Page 3Linked to original sources

PubMed1998

Localization of colorectal carcinoma by rhenium-188-labeled B72.3 antibody in xenografted mice.

In order to evaluate the feasibility of 188Re-labeled antibodies for radioimmunotargeting, monoclonal antibody B72.3, recognizing TAG-72, expressed on the surface membranes of colorectal cancer cells, was directly labeled with 188Re, obtained from a 188W/188Re generator, using stannous tartrate and compared with 125I-labeled B72.3. As a control, a human IgG was also radiolabeled with 188Re and 125I. Prepared antibodies for 188Re labeling could be stored as kits. Biodistribution was determined in nude mice inoculated with human colorectal carcinoma LoVo. Labeling efficiency and immunoreactivity of 188Re-B72.3 were 80.3% and 64.7%, respectively. 188Re-B72.3 localized specifically in the LoVo tumors. Although the absolute tumor accumulation level of 188Re-B72.3 was lower than 125I-B72.3, 188Re-B72.3 demonstrated higher tumor-to-blood contrast than the 125I-labeled counterpart, 2.04 +/- 0.44 vs. 1.05 +/- 0.28 at 96 hours, because of fast clearance from the blood. 188Re-B72.3 seemed efficient for the imaging and therapy of colorectal carcinoma.

Animals↗

PubMed1998

Pentavalent rhenium-188 dimercaptosuccinic acid for targeted radiotherapy: synthesis and preliminary animal and human studies.

Pentavalent rhenium-188 dimercaptosuccinic acid [188Re(V)DMSA] is a beta-emitting analogue of 99mTc(V)DMSA, a tracer that is taken up in a variety of tumours and bone metastases. The aim of this study was to develop the kit-based synthesis of the agent on a therapeutic scale, to assess its stability in vivo, and to obtain preliminary biodistribution and dosimetry estimates, prior to evaluation of its potential as a targeted radiotherapy agent. The organ distribution of 188Re in mice was determined 2 h after injection of 3 MBq 188Re(V)DMSA prepared from eluate from a 188W/188Re generator. Three patients with cancer of the prostate and three with cancer of the bronchus, all with bone metastases confirmed with a standard 99mTc-hydroxymethylene diphosphonate (99mTc-HDP) scan, were given 370 MBq 188Re(V)DMSA and imaged at 3 h and 24 h using the 155-keV gamma-photon (15%). Blood and urine samples were collected to determine clearance and to analyse the speciation of 188Re. Organ residence times were estimated from the scans, and used to estimate radiation doses using MIRDOSE 3. In mice, 188Re(V)DMSA was selective for bone and kidney. In patients, it showed selectivity for bone metastases (particularly those from prostate carcinoma) and kidney, but uptake in normal bone was not significantly greater than in surrounding soft tissues. Of the normal tissues the kidneys received the highest radiation dose (0.5-1.3 mGy/MBq). The images were strongly reminiscent of 99mTc(V)DMSA scans in similar patients. High-performance liquid chromatography analysis of blood and urine showed no evidence of 188Re in any chemical form other than 188Re(V)DMSA up to 24 h. In conclusion, 188Re(V)DMSA and its 186Re analogue warrant further clinical assessment as generator/kit-derived agents for treatment of painful bone metastases. These agents should also be assessed in medullary thyroid carcinoma and other soft tissue tumours which have been shown to accumulate 99mTc(V)DMSA.

Aged↗

PubMed1998

Reactor-produced radioisotopes from ORNL for bone pain palliation.

The treatment of painful skeletal metastases is a common clinical problem, and the use of therapeutic radionuclides which localize at metastatic sites has been found to be an effective method for treatment of pain, especially for multiple sites for which the use of external beam irradiation is impractical. There are currently several metastatic-targeted agents radiolabeled with various therapeutic radionuclides which are in various stages of clinical investigation. Since neutron-rich radionuclides are produced in research reactors and often decay by emission of beta- particles, most radionuclides used for bone pain palliation are reactor-produced. Key examples of radionuclides produced by single neutron capture of enriched targets include rhenium-186 and samarium-153. In addition, generator systems are also of interest which provide therapeutic daughter radionuclides from the decay of reactor-produced parent radionuclides. One important example is rhenium-188, available from generators via decay of reactor-produced tungsten-188. Tin-117m is an example of a reactor-produced radionuclide which decays with the emission of low-energy conversion electrons rather than by beta- decay. Each of these agents and/or radionuclides has specific advantages and disadvantages, however, the ideal agent for bone pain palliation has not yet been identified. The goal of this paper is to briefly review the production and use of several reactor-produced radionuclides for bone pain palliation, and to discuss the role of the ORNL High Flux Isotope Reactor (HFIR) for the production of many of these radionuclides.

Bone Neoplasms↗

PubMed1998

Evaluation and metabolite studies of 125I- and 123I-labelled E-(R,R)-IQNP: potential radioligands for visualization of M1 muscarinic acetylcholine receptors in brain.

A new ligand for the M1 muscarinic receptor subtype, E-(R,R)-1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (E-IQNP), was labelled with 125I and 123I for autoradiographic studies on human whole-brain cryosections and SPET studies, respectively, in Cynomolgus monkey. Autoradiography demonstrated E-[125I]IQNP binding in M1 receptor-rich regions such as the neocortex and the striatum. The binding was displaceable by the selective M1 antagonist biperiden. In vivo single photon emission tomography (SPET) studies with E-[123I]IQNP demonstrated a high accumulation of radioactivity in the monkey neocortex. Rapid hydrolysis of the quinuclidinyl ester to the free acid was found to be a major biotransformation route for E-[123I]IQNP. The free acid of E-[123I]IQNP does not pass the blood-brain barrier, but the plasma concentration was high as compared to the total radioactivity in brain. It is thus necessary to correct for the high concentration of radioactive metabolites in parenchymal blood (CBV) to obtain accurate values for E-[123I]IQNP binding in brain.

Animals↗

PubMed1998

188Re- and 99mTc-MAG3 as prosthetic groups for labeling amines and peptides: approaches with pre- and postconjugate labeling.

Either radiolabeled Tc-99m- or Re-188-labeled MAG3-4-nitrophenylester or unlabeled Bz-MAG3-4-nitrophenylester was reacted with amines and peptides to follow a pre- or a postconjugate radiolabeling route, respectively. The model compounds were N'-t-butyloxycarbonyl-1,6-diaminohexane (DH-Boc) and a Lys-protected derivative of the somatostatin analog RC-160 (cyclic D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2). In the case of labeling DH-Boc, both the preconjugate labeling and the postconjugate labeling were found by using analytical HPLC to provide identical radiolabeled compounds regardless whether Re-188 or Tc-99m was used. The results are supported by infrared and mass-spectral data obtained from compounds synthesized using stable rhenium. The 188Re- or 99mTc-MAG3-RC-160 somatostatin analog were synthesized following the preconjugate labeling route and subsequent removal of the protecting group. Biodistributions of 188Re-and 99mTc-MAG3-RC-160 were evaluated in normal and tumor-bearing mice, and were similar to those of radioiodinated 131-RC-160. All radiolabeled analogs of RC-160 were rapidly cleared from the blood and were excreted through the hepatobiliary system with very little normal organ uptake. The tumor uptake (PC-3, human prostate adenocarcinoma) of systemically administered Re-188-MAG3-RC160 was very low, and it reached only 0.28% injected dose/g (%IDg) at 24 h postinjection, similar to what was obtained with I-131-RC-160. Intratumor injections resulted in significant tumor retentions (9.3% ID/g at 24 h).

Amines↗

PubMed1998

Rhenium-188--a generator-derived radioisotope for cancer therapy.

Rhenium-188 (188Re) is an important therapeutic radioisotope which is obtained on demand as carrier-free sodium perrhenate by saline elution of the tungsten-188/rhenium-188 generator system. With a half-life of 16.9 hours and emission of a high energy beta particle (maximal energy of 2.12 MeV) and a gamma photon (155 keV, 15%) for imaging, 188Re can be provided at reasonable costs for routine preparation of radiopharmaceuticals for cancer treatment.

Half-Life↗

PubMed1998

Rhenium-188 microspheres: a new radiation synovectomy agent.

Radiation synovectomy is efficacious in controlling the symptoms of rheumatoid arthritis. However, the procedure is not widely used because of concerns about leakage of radiopharmaceuticals from the treated joints. Leakage can be minimized by selecting particles of an appropriate size. In this study, we labelled microspheres with 188Re and analysed its biodistribution after intra-articular injection in rabbits with antigen-induced arthritis. Gamma camera imaging was performed to quantify the mean retention of 188Re in the knees. The mean retention of 188Re was 98.7, 94.6 and 93.6% at 1, 24 and 48 h, respectively. The biodistribution data revealed very low radioactivity in all organs at different times, which suggests the leakage of radiotracer from the knee was negligible. Our preliminary results indicate that 188Re microspheres are a potentially effective radiopharmaceutical for radiation synovectomy.

Animals↗

PubMed1998

Pharmacokinetics of 99Tcm-pertechnetate and 188Re-perrhenate after oral administration of perchlorate: option for subsequent care after the use of liquid 188Re in a balloon catheter.

Radioactive wires and other linear sources are currently being used in clinical trials as endovascular brachytherapy to prevent restenosis after percutaneous transluminal coronary angioplasty. A new concept is the use of a liquid-filled balloon containing a beta-emitting radioisotope. A major advantage is optimal delivery of the radioactivity to the vessel wall. Rhenium-188 (188Re) is a high-energy beta-emitter that is routinely available from a 188W/188Re generator in liquid form. Since 188Re-perrhenate could be released in the unlikely event of balloon rupture, we investigated whether, in analogy to pertechnetate, subsequent use of perchlorate can reduce the uptake of perrhenate in the thyroid. We performed static (n = 9) and dynamic (n = 11) thyroid scintigraphy with 99Tcm-pertechnetate to estimate the overall reduction in activity within 30 min and the washout from the thyroid after oral administration of 600 mg perchlorate (T1/2). In two patients, 188Re was injected to estimate the whole-body distribution and the discharge of thyroid activity after perchlorate use. Based on MIRD Dose Estimate Report No. 8 (valid for 99Tcm-pertechnetate), the radiation burden was calculated for intravenous administration of 188Re and competitive blocking with perchlorate. In 20 patients, 99Tcm uptake by the thyroid was reduced by 85% within 30 min by perchlorate. The mean (+/- S.D.) washout rate (T1/2) was 8 +/- 2 min in 11 patients. Perrhenate showed a whole-body distribution similar to that of pertechnetate and the thyroid activity could be displaced (T1/2 = 6.3 and 9.3 min, respectively) by oral administration of perchlorate, with reductions in uptake of 83% and 75% within 30 min, respectively. Whole-body scanning demonstrated no regional accumulation of 188Re-perrhenate with excretion by urine. Dose estimates gave an effective dose equivalent of 0.42 mSv MBq-1, which decreased to 0.16 mSv MBq-1 after perchlorate blocking. 188Re has favourable properties for endovascular brachytherapy via a balloon catheter and, in the unlikely event of balloon rupture, whole-body radiation can be reduced to 38% by subsequent oral administration of perchlorate.

Administration, Oral↗

PubMed1998

Increased uptake of iodine-123-BMIPP in chronic ischemic heart disease: comparison with fluorine-18-FDG SPECT.

UNLABELLED: To evaluate the potential role of 15-p-[123I]iodophenyl-3-(R,S)-methylpentadecanoic acid (BMIPP) for the assessment of myocardial viability, the patterns of BMIPP versus 18F-fluorodeoxyglucose (FDG) uptake were evaluated in patients with chronic ischemic heart disease. METHODS: Twenty-one patients with stable chronic coronary artery disease underwent resting TI SPECT to delineate myocardial perfusion followed by FDG SPECT to detect residual viability in regions showing perfusion defects. Resting BMIPP SPECT was obtained on a separate day. SPECT images were displayed as polar maps (13 segments) and analyzed semiquantitatively. A total of 273 segments were analyzed. RESULTS: In 87 (32%) of the segments, a perfusion defect was observed. In perfusion defects, the distributions of BMIPP/TI (mis)matches were significantly different (p < 0.0001) between the FDG viable (n = 42) and nonviable (n = 45) segments. A BMIPP/TI mismatch (BMIPP uptake higher than perfusion) was found in 74% of FDG viable segments, whereas a BMIPP/TI match (BMIPP uptake equal or lower than perfusion) was found in 69% of FDG nonviable segments. Agreement between matching or mismatching of segments was assessed to be 71%. Agreement was 81% when the data were analyzed on a patient basis. The observed frequency of BMIPP/TI mismatches was significantly higher (p < 0.05) in segments with an old myocardial infarction (20 of 36; 55%) than it was in subacute infarcted myocardium (5 of 21; 24%). CONCLUSION: In chronically hypoperfused myocardium, an increased BMIPP uptake relative to perfusion was detected, which is different from the decreased BMIPP uptake often reported in (sub)acute myocardial ischemia. Therefore, the interval from infarction may be an important factor in the interpretation of BMIPP scintigraphic data. Increased BMIPP uptake was associated with FDG/TI mismatches and may, therefore, confirm myocardial viability. Some segments with a FDG/TI mismatch, however, revealed a BMIPP/TI match. These segments may contain viable but more severely damaged tissue. Further studies on functional recovery are warranted to assess the significance of a BMIPP/perfusion (mis)match for tissue viability.

Aged↗

PubMed1998

[Dosimetry fundamentals of endovascular therapy using Re-188 for the prevention of restenosis after angioplasty].

AIM: Various radionuclides can be used for endovascular brachytherapy. A new concept is to inflate the balloon of a dilatation catheter with a radioactive solution. Re-188 can be eluted from a generator system and is available daily. The aim of this study was to obtain dosimetric data for this radionuclide. METHODS: The dose decrease of Re-188 was calculated and measured with a TLD-system radial to a balloon catheter typically used in cardiology (diameter: 3 mm, length: 20 mm). RESULTS: Using a specific activity of 370 MBq/ml a dose of 0.3 Gy could be achieved within 1 min in a TLD in contact with the balloon. Paired TLDs differed about 3%. A fast dose reduction of 50% and 10% were stated within 0.5 mm and 2.5 mm, respectively. Calculated and measured values were in good agreement. The data are comparable to those known for Y-90. CONCLUSION: Calculations of dose distribution are consistent with TLD measurements of Re-188. Using a specific activity of 1.85 GBq/ml, a dose of 10-15 Gy at the coronary artery wall can be achieved within 2-3 min. Compared to radioactive stents or wires the use of this liquid beta-emitter is a simple alternative for prevention of the restenosis following the angioplasty.

Angioplasty, Balloon↗

PubMed1998

Intra-individual comparison of 3(R)-BMIPP and 3(S)-BMIPP isomers in humans.

UNLABELLED: The racemic 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) is currently used at several centers for myocardial metabolic imaging with SPECT. Recently, the 3(R)-BMIPP isomer showed a 20%-25% higher myocardial uptake and lower liver uptake than 3(S)-BMIPP in fasted rats. The aim of this study was to determine if these differences in myocardial and liver uptake also occur in humans. METHODS: Iodine-123-labeled 3(R)-BMIPP and 3(S)-BMIPP isomers were injected at rest, on two separate days, in six patients with stable coronary artery disease. Dual-head, whole-body scintigraphy was performed 20 min and 3 hr after injection. SPECT cardiac imaging was performed 60 min after injection. RESULTS: Myocardial activity averaged (% injected dose +/- s.d.) 3.15 +/- 0.49 versus 3.01 +/- 0.44 at 20 min (p = ns) and 2.64 +/- 0.38 versus 2.55 +/- 0.41 at 3 hr postinjection (p = ns) for the 3(R)-BMIPP and 3(S)-BMIPP isomers, respectively. Liver activity averaged 9.50 +/- 1.18 versus 9.44 +/- 0.66 at 20 min and 5.33 +/- 0.64 versus 5.43 +/- 0.66 at 3 hr, respectively (p = ns). SPECT showed no difference in the distribution of the two isomers between normal and infarcted myocardium. CONCLUSION: There is no significant difference in myocardial and liver distribution of the 3(R)-BMIPP and 3(S)-BMIPP isomers in humans.

Coronary Disease↗

PubMed1998

Intratumoral injection of rhenium-188 microspheres into an animal model of hepatoma.

UNLABELLED: Intratumoral injection of 90Y microspheres is a potential alternative in the treatment of primary liver tumor. However, complicated preparation and lack of a gamma ray for imaging are the disadvantages of 90Y. In this study, we used 188Re, a generator-produced radioisotope with 155-keV gamma ray emission, to label microspheres. After intratumoral injection of 188Re microspheres into rats with hepatoma, biodistributions and survival times were analyzed. METHODS: Twelve male rats with hepatoma were killed at 1, 24 and 48 hr (4 rats at each time point) after intratumoral injection of approximately 7.4 MBq 188Re microspheres. Samples of various organs were obtained and used to calculate the tissue concentrations. In addition, 30 male rats bearing hepatoma were divided into two groups (15 rats in each group) to evaluate survival time. Group 1 received intratumoral injection of 37 MBq 188Re microspheres, whereas Group 2 served as the control group and received an intratumoral injection of 0.1 ml normal saline only. Survival time was calculated from the day of injection to 2 mo after treatment. RESULTS: Radioactivity in the tumor was very high throughout. Biological half-time was 170.8 hr. Radioactivity in the lung was 1.78% injected dose (i.d.)/g at 1 hr but declined rapidly over time. The concentration in the urine was approximately 6.14% i.d./ml after the first hour and rapidly declined thereafter. The concentrations of radioactivity in other organs, such as normal liver, muscle, spleen, bone, testis and whole blood, were quite low throughout the study. Twelve of 15 (80%) of rats survived over 60 days after intratumoral injection of 188Re microspheres, whereas only 4 of 15 (26.7%) survived more than 60 days after injection of normal saline only. The difference between the groups was significant (p < 0.05). CONCLUSION: Rhenium-188 offers cost-effectiveness, on-site availability, short half-life, energetic beta particle, emission of gamma photons for imaging, easy preparation, easy clinical administration and apparent lack of radiation leakage from the treated tumor. Direct intratumoral injection of 188Re microspheres is extremely attractive as a clinical therapeutic alternative in hepatoma patients.

Animals↗

PubMed1997

Rhenium-188 hydroxyethylidene diphosphonate: a new generator-produced radiotherapeutic drug of potential value for the treatment of bone metastases.

The search for an ideal radioisotope for systemic radiotherapy continues. As a generator-produced radioisotope emitting both beta and gamma rays and having a short physical half-life of 16.9 h, rhenium-188 is a very good potential candidate for systemic radiotherapy. In this study, we labeled hydroxyethylidene diphosphonate (HEDP) with 188Re and analyzed the biodistribution and bone uptake following intravenous injection in rats to assess its potential for clinical use. The rats were injected with approximately 14.8 MBq (0.4 mCi) 188Re-HEDP in a volume of 0.1 ml intravenously and then sacrificed at 1 h, 24 h, or 48 h (four rats at each time). Samples (about 0.1 g) of lung, liver, kidney, spleen, testis, muscle, stool, and bone (thoracic vertebra) were taken and weighed carefully. In addition, a 1-ml sample of blood was drawn from the heart and 1 ml of urine was taken from the urinary bladder immediately after killing. Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter (% ID/g or ml). Bone lesions were created in the right tibial bone in three rabbits to calculate the lesion to normal uptake ratio (L/N ratio). The biodistribution data showed that the radioactivity in the bone tissue was as high as 1.877% ID/g at 1 h and that it climbed to 2.017% ID/g at 4 h. The activity level in the kidney was highest at 1 h but declined rapidly throughout the study. The radioactivities in the lung, liver, muscle, spleen, testis, blood, and stool were all lower than 0.3% ID/g at 1 h and also declined rapidly. The biological half-life in bone was the longest (60.86 h). In contrast, the biological half-lives in muscle and blood were short (2.99 h and 6.21 h respectively). The concentrations of radioactivity in muscle, spleen, testis, and stool were quite low throughout the study. Most of the radiotracer was excreted by the urinary system. The L/N ratio was 4.23+/-0.21 in rabbits injected with 188Re-HEDP and 4.25+/-0.23 in those injected with technetium-99m methylene diphosphonate. In conclusion, we would suggest that 188Re-HEDP is a very good potential candidate for the treatment of bone metastases because of the following characteristics: (1) it is generator produced; (2) it has a short half-life; (3) it emits gamma rays suitable for imaging; (4) there is highly selective uptake in the skeletal system and bone lesions; and (5) it has a low non-target uptake and rapid clearance in nonosseous tissue.

Animals↗

PubMed1997

Positron emission tomographic investigations of central muscarinic cholinergic receptors with three isomers of [76Br]BrQNP.

We studied the potential of three radiobrominated isomers of BrQNP, (Z(-,-)-[76Br]BrQNP, E(-,-)-[76Br]BrQNP and E(-,+)-[76Br]BrQNP), as suitable radioligands for imaging of central muscarinic cholinergic receptors in the human brain. These radioligands were stereospecifically prepared by electrophilic radiobromodestannylation of the respective tributylstannyl precursors using no-carrier-added [76Br]BrNH4 and peracetic acid. Preliminary pharmacological characterizations were determined by biodistribution, autoradiography, competition, displacement and metabolite studies in rats. The (-,-)-configuration presented important specific uptakes in brain muscarinic cholinergic receptor (mAChR)-rich structures and in heart, low metabolization rates and an apparent M2 selectivity. The (-,+)-configuration revealed more rapid clearance, lower uptake, a higher metabolization rate and an apparent M1 selectivity. Reversibility of the binding was confirmed for the three radiotracers. Positron emission tomography in the living baboon brain revealed high and rapid uptake in the brain and accumulation in the mAChR-rich structures studied. At 30 min p.i., the E(-,-)-radiotracer reached a plateau in cortex, pons and thalamus with concentrations of 29%, 24% and 19% ID/l, respectively. Z(-,-)-[76Br]BrQNP also accumulated in these structures, reaching a maximal uptake (27% ID/l) in the cortex 2 h p.i. At 5 min p.i. a plateau (17% ID/l) was only observed in the cortex for the E(-, +)-[76Br]BrQNP; by contrast, the other structures showed slow washout. After 3 weeks, the (-,-)-radiotracers were studied in the same baboon pretreated with dexetimide (1 mg/kg), a well-known muscarinic antagonist. In all the mAChR structures, the highly reduced uptake observed after this preloading step indicates that these radiotracers specifically bind to muscarinic receptors. Z(-, -)-[76Br]BrQNP, which is displaced in higher amounts from M2 mAChR-enriched structures, reveals an M2 affinity. The two isomers having the (-,-)-configuration are potential probes for investigating central muscarinic receptors. The absolute configuration on the acetate chiral centre influences their muscarinic subtype selectivity and the cis-trans isomerism of the vinyl moiety affects their specific fixation.

Animals↗

PubMed1997

Preparation of 188Re-RC-160 somatostatin analog: a peptide for local/regional radiotherapy.

Conditions are described for the preparation of 188Re-RC-160, a radiolabeled synthetic peptide derived from an analogue of somatostatin, using a lyophilized labeling kit containing RC-160 (200 micrograms) and stannous tartrate to which is added carrier-free 188Re (beta, Emax, 2.12 MeV; gamma, 155 keV, 10%; T1/2 = 16.7 h). The kits have been radiolabeled with > 2960 MBq (80 mCi) with a high labeling efficiency and no need for subsequent purification. Radiolabeling results in one major peak when analyzed by reverse-phase (RP) HPLC. Presumptive radiolysis was detected at 2.5 h post-labeling; however, a convenient method is described for stabilizing the kits against radiolysis by the post-labeling addition of ascorbic acid.

Antineoplastic Agents↗

PubMed1997

Radiolabeling antibodies with holmium-166.

We report the preliminary results from radiolabeling of a chelate-conjugated antibody with 166Ho produced from the beta(-)-decay of 166Dy. Ho-166 was separated from mg quantities of Dy target by reverse phase ion-exchange chromatography employing a cation exchange HPLC column and 0.085 M alpha-HIBA at pH = 4.3 as eluent. Evaporation to dryness of 166Ho fraction (up to 25 mL) and thermal decomposition of alpha-HIBA yielded 166Ho in a dry state which was then solubilized in 0.5 mL of 0.1 M HCl. Subsequent radiolabeling of CHX-B-DTPA conjugated 135-14 monoclonal antibodies with purified 166 Ho was readily achieved with approximately 80% efficiency and with a specific activity of 3-4 mCi of 166Ho per mg of protein. 166Ho-antibody conjugates are stable with regards to transferrin challenge for a period of 50 h. Further, it was shown that any Fe3+ ions present in alpha-HIBA as an impurity interfere with the labeling.

Antibodies, Monoclonal↗

PubMed1997

Targeting peptides for pleural cavity tumor radiotherapy: specificity and dosimetry of Re-188-RC-160.

Re-188-RC-160, a radiolabeled somatostatin analogue, is being explored for its potential as a local/regionally administered radiotherapeutic agent targeting somatostatin receptor-positive tumors. In studies in vitro and in vivo, Re-188-RC-160 was found to bind to somatostatin receptor-positive cells (NCI-H69, human small cell lung carcinoma), but not to binding-negative cells (Raji, Burkitt's lymphoma). The comparative binding of Re-188-labeled RC-160 [cyclic NH2-(D)-Phe-Cys-Try-(D)-Trp-Lys-Val-Cys-Trp-NH2] or CTOP [cyclic NH2-(D)-Phe-Cys-Try-(D)-Trp-Orn-Thr-Pen-Thr-ol], a mu-opioid receptor antagonist used a negative control compound, was also determined in vitro and in vivo using NCI-H69 cells as targets. Re-188-RC-160 demonstrated higher net binding in vitro and in vivo compared to Re-188-RC-CTOP, and in vitro its binding could be reduced by excess unlabeled RC-160 whereas binding of Re-188-CTOP could not be reduced. Using another somatostatin receptor-positive human tumor line, ZR-75-1, a substantial amount of the cell-bound Re-188-RC-160 was found to be internalized. Does estimates for Re-188-RC-160 in animals containing NCI-H69 tumors indicated that with three serial injections therapeutic doses greater than 60 Gy can be achieved.

Animals↗

PubMed1997

Evaluation of heart-to-organ ratios of 123I-BMIPP and the dimethyl-substituted 123I-DMIPP fatty acid analogue in humans.

Radioiodinated fatty acid analogues modified by methyl-substitution are used for single photon emission tomography (SPET) imaging of the heart. The effect of mono- and dimethyl-substitution on heart-to-organ ratios was investigated in humans to evaluate their relative merits for SPET image quality. Planar total body scans were performed in fasting patients with coronary artery disease, but without heart failure, 1 h after administration of 111 MBq 15-(p-[I-123]-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP, n = 7) or 111 MBq 15-(p-[I-123]-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP, n = 4). Because these branched fatty acids are used for cardiac imaging, we focused on heart-to-organ (heart/organ) ratios by comparing small regions of interest in heart, liver, lung, muscle and bladder. Both tracers showed good visualization of the heart. DMIPP showed a relatively high liver uptake: the heart/liver ratios for DMIPP and BMIPP were 0.39 +/- 0.05 and 1.00 +/- 0.12, respectively (P < 0.0001). Increased lung activity was found for BMIPP, with a heart/lung ratio of 1.63 +/- 0.17 versus 2.32 +/- 0.28 for DMIPP (P < 0.001). In contrast to DMIPP, BMIPP also showed increased activity in the bladder. In conclusion, BMIPP and DMIPP show different distribution patterns. Despite the more favourable heart/lung ratios for DMIPP, the high liver uptake affects cardiac SPET image quality and therefore BMIPP appears to provide superior cardiac SPET image quality in humans.

Blood Glucose↗