To explore the preparation method of liposome-mediated 99m-technetium-labeled antisense oligonucleotides of c-myc mRNA and lay foundations for antisense imaging and treatment, antisense oligonucleotides (DNA) with 15 bases and di-functional chelate, hydrazino nicotinamide derivatives, were synthesized. After DNA combined with chelate, they were labeled with 99m-technetium to form compounds, 99mTc-chelate-DNA (99mTc-DNA), and were purified through Sep-Pak reverse column(C18, Waters) by using methanol and water as eluent. The leaching curve was made; the labeling efficiency was calculated. The products were then encapsulated with cation liposome to form liposome-mediated 99mTc-DNA. The radiochemical purity and stability of the liposome-mediated 99mTc-DNA were tested through strip chromatography. The labeling efficiency was 63.37% +/- 3.51% at the radioactive concentration of 1480 MBq, 62.52% +/- 3.69% at that of 740 MBq, 59.82% +/- 5.12% at that of 592 MBq. There were no significant differences between these labeling efficiencies. The radiochemical purity was 96.47% +/- 3.01%. The liposome-mediated radiolabeled antisense oligonucleotides were stable after incubation with water or serum. Therefore liposome-mediated radiolabeled antisense oligonucleotides could be obtained through hydrazino nicotinamide derivatives as di-functional chelate and liposome as vector.
DNA, Antisense ; chemical synthesis ; Drug Compounding ; methods ; Drug Stability ; Isotope Labeling ; methods ; Liposomes ; Proto-Oncogene Proteins c-myc ; genetics ; RNA, Messenger ; genetics ; Technetium

BACKGROUNDTo study the clinical effects of ¹⁵³Sm-EDTMP plus chemotherapy in the treatment of bone metastasis of lung cancer.

METHODSOne hundred and ten lung cancer patients with one metastasis [male 82 and female 28, aged from 32 to 76 yrs; squamous cell carcinoma 28, adenocarcinoma 27, small cell lung cancer (SCLC) 7, mix type 41, alveolar carcinoma 7] who did not undergo an operation were entered into this study. The patients were divided into 3 groups: ¹⁵³Sm-EDTMP therapy only (37 cases), ¹⁵³Sm-EDTMP plus chemotherapy after 3 days (42 cases), 30 days after chemotherapy plus ¹⁵³Sm-EDTMP (31 cases). The dosages of ¹⁵³Sm-EDTMP ranged from 1 111 to 2 660 MBq. The patients with SCLC were adapted CCNU, MTX and CTX; those with non-small cell lung cancer (NSCLC) were adapted MMC, VCR and DDP. Statistic analysis of the data was performed by Chi-square test.

RESULTSTotal pain relief rate for ¹⁵³Sm-EDTMP only was 89.2% , for ¹⁵³Sm-EDTMP plus chemotherapy was 92.8%, and for chemotherapy plus 153 Sm EDTMP was 90.3% . The foci disappeared in 9 cases with ¹⁵³Sm-EDTMP only, in 12 cases with ¹⁵³Sm-EDTMP plus chemotherapy, and in 9 cases with chemotherapy plus ¹⁵³Sm-EDTMP. The 1 year survival rate was 29.7%(11/37) by 153 Sm only, 40.5%(17/42) by 153 Sm plus chemotherapy, 38.7%(12/31) by chemotherapy plus ¹⁵³Sm-EDTMP.

CONCLUSIONS¹⁵³Sm-EDTMP plus chemotherapy is effective in the treatment of bone metastasis of lung cancer.

OBJECTIVETo evaluate the measurement of Samarium-153 ethylenediaminetetramethylene phosphonic acid ((153)Sm-EDTMP) bone uptake rate using whole-body scintigraphy and analyze the relationship between bone uptake rate and therapeutic effect.

METHODSSixty-six patients with painful bony metastases from prostate (n = 15), lung (n = 20), breast (n= 18), nasopharyngeal carcinoma (NPC) (n=5), colon (n=2), kidney (n=2) and unknown cause (n=4) carcinoma were examined with whole-body scintigraphy 10 min and 5 h post administration of (153)Sm-EDTMP. Bone uptake rate was then calculated. (1 ) Complete response (CR): disappearance of > 2 metastases, Karnofsky Performance Score (KPS) increase > 20, moderate or complete remission of bone pain 7 d post injection of (153)Sm-EDTMP. (2) Partial response (PR): disappearance of 1-2 metastases, KPS increase 10-20, moderate remission of bone pain in 3 wk. (3) Non-response (NR): no disappearance or shrinkage of metastases, KPS increase < 10, no or slight remission of bone pain.

RESULTSThe range of bone uptake rate in 66 patients was 31 .9% - 86.6% (mean = 56. 0%). The bone uptake rate in the CR group (17 cases, 25.7%), PR group (24 cases, 36.4%), and NR group (25 cases, 37.9%) was 52.4% - 86.6% (mean = 68.7%), 43.7% - 70.4% (mean = 58.3%), and 31.9%- 51 .5% (mean = 41 . 0%) respectively. Statistical analysis showed that there was a significant difference between the CR and PR groups ( t = 4.258, P = 0.001 ) as well as between PR and NR groups ( t = 8.48,P = 0.001 ).

CONCLUSIONSUsing a simple and reliable whole-body scintigraphic technique to calculate prospectively the bone uptake rate, we have, for the first time in China, reported the relationship between bone uptake rate and therapeutic effect. This allows nuclear medicine physicians to calculate a safe and effective dose of (153)Sm-EDTMPin individual patients to palliate bone cancer pain without myelotoxicity.

Bone Neoplasms ; drug therapy ; secondary ; Bone and Bones ; metabolism ; Female ; Humans ; Male ; Organometallic Compounds ; pharmacokinetics ; therapeutic use ; Organophosphorus Compounds ; pharmacokinetics ; therapeutic use

Objective　This study was intended to investigate and compare technetium-99m-N,N′-ethylenebis(acetylacetoneiminato)bis〔tris (3-methoxy-1-propyl) phosphine〕 (99mTc-Q3) versus　201Tl on clearance and retention properties at varying coronary flow rates in isolated rabbit heart. Methods　 20 New Zealand White rabbits were anaesthetized and excised through a median sternotomy. The hearts were isolated and arrested in ice-cold saline. The external perfusion models with isolated rabbit hearts were installed and were perfused at flow rates ranging from 0.52 to 3.75 ml/(g wet wt*min) in the absence of tracer recirculation. Furthermore,99mTc-Q3 experimental relations between uptake, clearance and retention were explored in comparison with　201Tl.Results　201Tl net uptake was higher and also more affected by flow rates (P< 0.05 ) as compared with　99mTc-Q3 net uptake.201Tl clearance was faster than　99mTc-Q3 clearance within 4 to 25 minutes after radiopharmaceuticals injection in high flow rates group, and　201Tl clearance was faster than　99mTc-Q3 clearance within 40 minutes after radiopharmaceuticals injection in low flow rates group.201Tl earlier rapid clearance observed in the high flow rates group did not appear in the low flow rates group, but　99mTc-Q3 did not display early rapid clearance either in the high flow rates group or in the low flow rates group. Conclusion　 Owing to faster clearance, the superiority of　201Tl over　99mTc-Q3 as a myocardial perfusion imaging agent would be lost entirely within 10 minutes after injection of agent, therefore　99mTc-Q3 is still a good myocardial perfusion imaging agent, and further study is worth doing.