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Book ; Conference proceedings: Program and abstracts / The Seventh International Symposium on Radiopharmacology

Hnatowich, D. J.

Boston, Massachusetts, 3 - 6 June 1991

1991

Event/congress	International Symposium on Radiopharmacology (7, 1991, BostonMass.)
Author's details	conference committee D. J. Hnatowich, conference chairperson
Keywords	Radiopharmaceuticals / pharmacokinetics / congresses
Language	English
Size	82 Bl. : graph. Darst.
Publishing place	S.l.
Publishing country	United States
Document type	Book ; Conference proceedings
HBZ-ID	HT008075921
Database	Catalogue ZB MED Medicine, Health

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Article: Observations on the role of nuclear medicine in molecular imaging.

Hnatowich, D J

Journal of cellular biochemistry. Supplement

2002 Volume 39, Page(s) 18–24

Abstract: The phrase "molecular imaging" is unquestionably current and is receiving ever increasing use. For example, two organizations, the Institute for Molecular Imaging and the Academy of Molecular Imaging have recently been established with molecular imaging ... ...

Abstract	The phrase "molecular imaging" is unquestionably current and is receiving ever increasing use. For example, two organizations, the Institute for Molecular Imaging and the Academy of Molecular Imaging have recently been established with molecular imaging as their focus, with journal entitled "Molecular Imaging" and "Molecular Imaging and Biology," respectively. Furthermore, the two leading journals in the field of nuclear medicine have recently added this phrase to their covers-becoming the "European Journal of Nuclear Medicine and Molecular Imaging" and "The Journal of Nuclear Medicine-advancing molecular imaging." The National Institute of Biomedical Imaging and Bioengineering is the newest institute of the NIH. With this degree of attention, it may be surprising that there is as yet no universally accepted definition of molecular imaging. Numerous diverse definitions, some quite complex, have been proposed. With some exceptions, they all refer to imaging in the living animal of function at the cellular or molecular level. Thus molecular imaging may be defined as the observation of biological function at the molecular level in health and disease through some process involving non-invasive imaging of the living mammals.
MeSH term(s)	Animals ; Diagnostic Imaging/instrumentation ; Diagnostic Imaging/methods ; Diagnostic Imaging/trends ; Gene Expression Profiling/methods ; Humans ; Nuclear Medicine/instrumentation ; Nuclear Medicine/methods ; Nuclear Medicine/trends
Language	English
Publishing date	2002
Publishing country	United States
Document type	Journal Article ; Review
ISSN	0733-1959
ISSN	0733-1959
DOI	10.1002/jcb.10400
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Antisense imaging: where are we now?

Hnatowich, D J

Cancer biotherapy & radiopharmaceuticals

2000 Volume 15, Issue 5, Page(s) 447–457

Abstract: The field of antisense targeting is changing rapidly as additional results from in vitro studies and animal and patient trials become available. While these developments apply primarily to antisense chemotherapy, many have implications for antisense ... ...

Abstract	The field of antisense targeting is changing rapidly as additional results from in vitro studies and animal and patient trials become available. While these developments apply primarily to antisense chemotherapy, many have implications for antisense imaging and radiotherapy. It may now be profitable to reconsider antisense imaging in the light of these recent developments. With the benefit of further insight, it may be possible to predict which antisense mechanisms will be preferable for antisense imaging. It is also possible to consider the influences of carriers (vectors) on the targeting of antisense DNA and whether this might improve imaging. Furthermore, estimates showing only low mRNA steady-state copy numbers per cell may be reconsidered in refining predictions of tissue counting rates. Finally, recent results suggest that radiolabeling antisense DNAs may not adversely influence the targeting properties of antisense DNAs.
MeSH term(s)	DNA, Antisense/drug effects ; DNA, Antisense/metabolism ; Genetic Vectors/therapeutic use ; Protein Biosynthesis/drug effects ; RNA, Messenger/metabolism ; Radionuclide Imaging/methods ; Radionuclide Imaging/trends
Chemical Substances	DNA, Antisense ; RNA, Messenger
Language	English
Publishing date	2000-10
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	1315649-4
ISSN	1084-9785
ISSN	1084-9785
DOI	10.1089/cbr.2000.15.447
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Article: Changing focus: applying antisense to nuclear medicine imaging.

Hnatowich, D J

Molecular medicine today

1999 Volume 5, Issue 4, Page(s) 151

MeSH term(s)	Humans ; Oligonucleotides, Antisense/therapeutic use ; Radiopharmaceuticals/therapeutic use ; Radiotherapy
Chemical Substances	Oligonucleotides, Antisense ; Radiopharmaceuticals
Language	English
Publishing date	1999-04
Publishing country	England
Document type	Congress ; Letter
ZDB-ID	1281487-8
ISSN	1878-4178 ; 1357-4310
ISSN (online)	1878-4178
ISSN	1357-4310
DOI	10.1016/s1357-4310(99)01449-5
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Article: [Preparation and quality control of 99mTc labeled MDR1 oligonucleotide DNAs].

Fan, Chengzhong / Hnatowich, D J

Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi

2008 Volume 25, Issue 3, Page(s) 712–715

Abstract: The aim of this study is to explore the optimal labeling condition of technetium-99m labeled antisense oligonucleotides (ASON) DNA and sense oligonueleotides (SON) DNA against multi-drug resistance gene-1 (MIDR1) mRNA, to prepare its two-step icefrozen ... ...

Abstract	The aim of this study is to explore the optimal labeling condition of technetium-99m labeled antisense oligonucleotides (ASON) DNA and sense oligonueleotides (SON) DNA against multi-drug resistance gene-1 (MIDR1) mRNA, to prepare its two-step icefrozen kits, and to perform the quality control of technetium-99m labeled ASON and SON DNAs and its two-step icefrozen kits. A 20 mer single-stranded ASON sequence and its SON sequence against MDR1 mRNA were synthesized respectively, both of the ASON and SON DNAs were uniform phosphorothioated for this investigation with a primary amine on the 5'-end via a six-carbon alkyl linker, and then were labeled with technetium-99m by conjugating with the bifunctional chelator S-Acetyl NHS-MAG3 to form ASON- and SON-MAC3 DNAs. The optimal labeling condition was explored by varying the amount of ASON- and SON-MAG3 DNAs, SnCl2.2H2O and buffer, the pH value in the reaction medium was also adjusted. The technetium-99m labeled ASON and SON DNAs' two-step icefrozen kits were developed. The radiochemical purities, labeling stability of ASON- and SON-MAG3 DNAs in vivo and vitro were measured, and stability of the two-step icefrozen kits were also studied. The recycled rates of ASON- and SON-MAG3 DNAs were over 70% (n >6), the two-step icefrozen kits of ASON- and SON-MAG3 DNAs were colourless ice crystal. The radiochemical purities of technetium-99m labeled ASON- and SON-MAG3 DNAs were over 92 %. The radiochemical purities were over 90% after stored at room temperature for 24 hours. The kits were stable within 6 months when stored at 0 degrees C, the radiochemical purities of technetium-99m labeled ASON- and SON-MAG3 DNAs were still over 90%. The two-step icefrozen kits of ASON- and SON-MAG3 DNAs were successfully developed. The radiochemical purities were all over 90%. The labeling method was simple, feasible and efficient with good stability.
MeSH term(s)	Animals ; DNA, Antisense/chemistry ; Isotope Labeling/methods ; Mice ; Mice, Nude ; Multidrug Resistance-Associated Proteins/chemistry ; Multidrug Resistance-Associated Proteins/pharmacokinetics ; Oligonucleotides, Antisense/chemistry ; Oligonucleotides, Antisense/pharmacokinetics ; Radiopharmaceuticals/chemical synthesis ; Radiopharmaceuticals/pharmacokinetics ; Random Allocation ; Technetium Tc 99m Mertiatide/chemistry ; Technetium Tc 99m Mertiatide/pharmacokinetics
Chemical Substances	DNA, Antisense ; Multidrug Resistance-Associated Proteins ; Oligonucleotides, Antisense ; Radiopharmaceuticals ; Technetium Tc 99m Mertiatide (36ITO9SKQJ) ; multidrug resistance-associated protein 1 (Y49M64GZ4Q)
Language	Chinese
Publishing date	2008-06
Publishing country	China
Document type	Journal Article
ZDB-ID	2576847-5
ISSN	1001-5515
ISSN	1001-5515
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Article: Antisense and nuclear medicine.

Hnatowich, D J

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

1999 Volume 40, Issue 4, Page(s) 693–703

Abstract: Despite many uncertainties concerning mechanism, synthetic single-strand antisense deoxyribonucleic acids (DNAs) are now in clinical trials for the chemotherapy of viral infections such as human immunodeficiency virus (HIV) and human papilloma virus; ... ...

Abstract	Despite many uncertainties concerning mechanism, synthetic single-strand antisense deoxyribonucleic acids (DNAs) are now in clinical trials for the chemotherapy of viral infections such as human immunodeficiency virus (HIV) and human papilloma virus; several cancers, including follicular lymphoma and acute myelogenous leukemia; inflammatory processes such as Crohn's disease and rheumatoid arthritis and in allergic disorders. There are approximately 10 trials, and early results are generally encouraging. Therefore, the expectation is that antisense DNAs will be important to future chemotherapy. The question considered here is whether antisense DNAs will also be important to future nuclear medicine imaging. While efforts toward developing antisense imaging are comparatively nonexistent thus far, investigations into the mechanisms of cellular transport and localization and the development of a second generation of antisense DNAs have occurred largely within the antisense chemotherapy industry. Fortunately, many of the properties of DNA for antisense imaging, such as high in vivo stability and adequate cell membrane transport, are the same as those for antisense chemotherapy. Unfortunately, interests diverge in the case of several other key properties. For example, rapid localization and clearance kinetics of the radiolabel and prolonged retention in the target are requirements unique to nuclear medicine. No doubt the development of antisense imaging will continue to benefit from improvements in the antisense chemotherapy industry. However, a considerable effort will be required to optimize this approach for imaging (and radiotherapy). The potential of specifically targeting virtually any disease or normal tissue should make this effort worthwhile.
MeSH term(s)	Animals ; DNA, Antisense/therapeutic use ; Humans ; Nuclear Medicine ; Radiopharmaceuticals
Chemical Substances	DNA, Antisense ; Radiopharmaceuticals
Language	English
Publishing date	1999-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80272-4
ISSN	1535-5667 ; 0161-5505 ; 0097-9058 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0161-5505 ; 0097-9058 ; 0022-3123
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Article: [Experimental study of 99mTc-antisense DNA for tumor imaging].

Fan, Chengzhong / Hnatowich, D J

Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi

2007 Volume 24, Issue 5, Page(s) 1142–1147

Abstract: This study was performed to explore the feasibility of antisense imaging with radiolabeled antisense oligonucleotides DNA in tumored nude mice in vivo. Two different tumor cell lines, KB-G2 and KB-31,were used; both antisense and control sense DNAs were ... ...

Abstract	This study was performed to explore the feasibility of antisense imaging with radiolabeled antisense oligonucleotides DNA in tumored nude mice in vivo. Two different tumor cell lines, KB-G2 and KB-31,were used; both antisense and control sense DNAs were administrated intratumorally. The hybridization activities analysis of MAG3 conjugated DNAs oligonucleotides was demonstrated by Polyacrylamide Gel Electrophoresis. The whole body imaging was performed 22 h after administration of radiolabeled antisense and control sense DNAs at 1.0 microg DNAs (100 microCi) in 100 microl per animal. Then the animals were sacrificed at 24 h after administration and the organs and tissues were dissected and weighed; the radioactivity of each sample was detected by r-counter; injection dose percentage per gram tissue (%ID/g) was calculated and the biodistribution obtained. Both MAGS conjugated oligonucleotides DNAs and natural oligonucleotides DNAs have the same hybridization activities. The whole body images demonstrate improved targeting of antisense DNAs vs sense DNAs in the KB-G2 but not the KB-31 animals. Tumor levels in the KB-G2 animals were significantly higher for the antisense DNAs vs sense DNAs (14.7 vs 8.5% ID/g) while this difference (8.6 vs 4.3% ID/g) was insignificant in the KB-31 animals. Evidence for tumor targeting in vivo by an antisense in that mechanism has been obtained; statistically higher tumor accumulations of the 99mTc-antisense DNA were observed when compared to the control 99mTc-sense DNA. The successful localization of antisense DNA in tumor demonstrates that antisense tumor targeting in vivo is feasible even though improvement in tumor delivery and normal tissue clearance are needed for practical antisense imaging.
MeSH term(s)	Animals ; Carcinoma, Squamous Cell/diagnostic imaging ; Carcinoma, Squamous Cell/pathology ; Dipeptides ; Electrophoresis, Polyacrylamide Gel ; Female ; Mice ; Mice, Nude ; Mouth Neoplasms/diagnostic imaging ; Mouth Neoplasms/pathology ; Oligodeoxyribonucleotides, Antisense/administration & dosage ; Oligodeoxyribonucleotides, Antisense/genetics ; Organometallic Compounds ; Radionuclide Imaging ; Tumor Cells, Cultured
Chemical Substances	Dipeptides ; Oligodeoxyribonucleotides, Antisense ; Organometallic Compounds ; technetium 99m mercapto-acetyl diglycine
Language	Chinese
Publishing date	2007-10
Publishing country	China
Document type	Journal Article
ZDB-ID	2576847-5
ISSN	1001-5515
ISSN	1001-5515
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Article: Pharmacokinetic considerations in the development of oligomers as radiopharmaceuticals.

Hnatowich, D J

The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)

1997 Volume 41, Issue 2, Page(s) 91–100

Abstract: Single-stranded oligomers are attractive candidates for the next generation of radiopharmaceuticals because of their ability to bind specifically to their complementary single-stranded oligomers by hybridization. However, native, phosphodiester DNAs have ...

Abstract	Single-stranded oligomers are attractive candidates for the next generation of radiopharmaceuticals because of their ability to bind specifically to their complementary single-stranded oligomers by hybridization. However, native, phosphodiester DNAs have been universally judged to be unsuitable because of excessive in vivo nuclease hydrolysis. Chemical modifications to phosphodiester DNAs are therefore required to improve pharmacokinetic properties before the potential of oligomers for radiopharmaceutical use can be realized. Fortunately, hundreds of modified oligomers have been prepared and tested, mostly in vitro, in connection with antisense chemotherapy. This chapter provides an overview of those results which are relevant to the use of the more important of these modified oligomers as radiopharmaceuticals. In brief, the phosphorothioate DNAs are stable in vivo but may be unsuitable in all forms because of high protein binding affinities which delay clearance and increase background radioactivity levels. The methylphosphonate DNAs are also stable but do not show high protein binding affinities. Like the vast majority of modified oligomers, they have not as yet been investigated as radiopharmaceuticals. However, it may be the synthetic oligomers which are the most attractive at present. In particular, PNA has been radiolabeled with 99mTc and shown in mouse studies to be stable, to clear rapidly without excessive protein binding and to hybridize to its complement in vivo. In conclusion, several oligomers display pharmacokinetic properties in preliminary studies which suggest that they deserve further consideration for use as radiopharmaceuticals.
MeSH term(s)	Animals ; DNA/chemical synthesis ; DNA/pharmacokinetics ; Mice ; Radiopharmaceuticals/pharmacokinetics
Chemical Substances	Radiopharmaceuticals ; DNA (9007-49-2)
Language	English
Publishing date	1997-06
Publishing country	Italy
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ISSN	1125-0135
ISSN	1125-0135
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Article: Pharmacokinetics of 99mTc-labeled oligonucleotides.

Hnatowich, D J

The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)

1996 Volume 40, Issue 3, Page(s) 202–208

Abstract: Oligonucleotides labeled with gamma-emitting radionuclides are likely to find eventual applications as radiopharmaceuticals. Accordingly, methods of radiolabeling single-stranded DNA by chelation with the gamma-emitting radionuclide 111In and, more ... ...

Abstract	Oligonucleotides labeled with gamma-emitting radionuclides are likely to find eventual applications as radiopharmaceuticals. Accordingly, methods of radiolabeling single-stranded DNA by chelation with the gamma-emitting radionuclide 111In and, more importantly, with 99mTc, have been developed. As an emerging technology, the results of only two pharmacokinetic investigations with 99mTc-labeled DNA have been reported thus far, both from this laboratory. This review focuses on the pharmacokinetic properties in mice of 99mTc when radiolabeled by one method (SHNH) to a 22-base native phosphodiester and phosphorothioate DNA. The labeled phosphodiester DNA displayed an affinity for proteins through its 99mTc-SHNH chelate. The affinity for proteins of the labeled phosphorothioate DNA was even greater and was attributed in this case to both the chelate and to the modified, and lipophilic, DNA backbone. As a consequence of this binding, and the recognized increased stability of the phosphorothioate DNA towards nucleases, probably explained the long-term retention of label in organs such as liver, spleen and kidney. In conclusion, under the conditions of these investigations, the labeled phosphodiester and phosphorothioate DNAs studied were both judged to be unsuitable for most applications as radiopharmaceuticals.
MeSH term(s)	Animals ; DNA, Single-Stranded/pharmacokinetics ; Humans ; Mice ; Oligonucleotides/pharmacokinetics ; Oligonucleotides, Antisense/pharmacokinetics ; Organotechnetium Compounds/pharmacokinetics ; Tissue Distribution
Chemical Substances	DNA, Single-Stranded ; Oligonucleotides ; Oligonucleotides, Antisense ; Organotechnetium Compounds
Language	English
Publishing date	1996-09
Publishing country	Italy
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S. ; Review
ISSN	1125-0135
ISSN	1125-0135
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Article: Is technetium-99m the radioisotope of choice for radioimmunoscintigraphy?

Hnatowich, D J

Journal of nuclear biology and medicine (Turin, Italy : 1991)

1994 Volume 38, Issue 4 Suppl 1, Page(s) 22–32

MeSH term(s)	Animals ; Humans ; Isotope Labeling/methods ; Radioimmunodetection ; Technetium
Chemical Substances	Technetium (7440-26-8)
Language	English
Publishing date	1994-12
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	80200-1
ISSN	0368-3249 ; 1121-1075 ; 0449-2846
ISSN	0368-3249 ; 1121-1075 ; 0449-2846
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