An early Phase II study of intratumoral P-32 chromic phosphate injection therapy for patients with refractory solid tumors and solitary metastases

Firusian, N; Dempke, Wolfram

doi:10.1002/(sici)1097-0142(19990215)85:4<980::aid-cncr28>3.0.co;2-h

Cited by 39 publications

(38 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Colloidal 32 P has been used for the treatment of intracavitary malignancies. The retention of radioactivity of colloidal 32 P at the site of a solid tumor required the infusion of macroaggregated albumin (19). An alternative method to aid radioactivity retention at the tumor site has been to use labeled, nontoxic and undegradable microcarriers such as phosphorus-32 glass microspheres (20).…”

Section: Discussionmentioning

confidence: 99%

“…The test substance, 32 P BioSilicon, an active implantable, radiological medical device with phosphorus 32 activity, was created by thermal neutron capture of highly phosphorus-doped silicon within a nuclear reactor, which transmutes the natural phosphorus ( 31 P) in the silicon lattice of BioSilicon to the h-emitting radionuclide 32 P. This is a similar process to that used by the semiconductor industry to dope silicon ingots and wafers with phosphorus, where the silicon 30 isotope is transmuted to phosphorus 31 (26). The activity of the product is 75 MBq nominal activity/100 mg BioSilicon (at reference date).…”

Section: P Biosiliconmentioning

confidence: 94%

“…Prior to administration, the device particles are suspended in a formulant which provides an even suspension of the intended dose for implantation. The primary objective of this animal trial study was to investigate the effects of intratumoral injection of 32 P BioSilicon on human hepatocellular (HepG2) and pancreatic carcinoma (2119) xenografts implanted in nude mice (BALB/c). A secondary objective was the histopathologic examination of the tumor foci and surrounding tissue during the study.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Complete Tumor Response Following Intratumoral 32P BioSilicon on Human Hepatocellular and Pancreatic Carcinoma Xenografts in Nude Mice

Zhang¹,

Loong

Connor³

et al. 2005

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose:32 P BioSilicon is a new, implantable, radiological medical device that comprises particles of highly pure silicon encapsulating 32 phosphorus ( 32 P) for the treatment of unresectable solid tumors. Prior to administration, the device particles are suspended in a formulant which provides an even suspension of the intended dose for implantation. The primary objective of this animal trial study was to investigate the effects of intratumoral injection of 32 P BioSilicon on human hepatocellular (HepG2) and pancreatic carcinoma (2119) xenografts implanted in nude mice (BALB/c). A secondary objective was the histopathologic examination of the tumor foci and surrounding tissue during the study. Methods: Cultured human carcinoma cells (HepG2 and 2119) were injected s.c. into the gluteal region of nude mice.When the implanted tumors were f1cm in diameter, 32 P BioSilicon (0.5, 1.0, and 2.0 MBq) or formulant was injected into the tumors. Implanted tumor size was measured once a week for 10 weeks. At study termination, the tumor and surrounding normal tissue were collected and fixed in 10% formalin and processed for histopathologic analysis. Results:32 P BioSilicon produced a reduction in HepG2 tumor volume when compared with formulant control, and complete response was observed among tumors in the 1.0 and 2.0 MBq treatment groups after week 8. There was also significant reduction in 2119 tumor volume in all treated groups, with the complete response rate of 67% in the 2.0 MBq group. Conclusion:32 P BioSilicon suppressed the growth of both human hepatocellular and pancreatic carcinoma xenografts implanted in nude mice and complete responses were also observed in tumors at higher radiation doses.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: P Biosiliconmentioning

confidence: 94%

mentioning

confidence: 99%

See 1 more Smart Citation

Complete Tumor Response Following Intratumoral 32P BioSilicon on Human Hepatocellular and Pancreatic Carcinoma Xenografts in Nude Mice

Zhang¹,

Loong

Connor³

et al. 2005

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Westlin and colleagues also treated patients with pancreatic tumours with 32 P colloid [2]. Firusian and Dempke used the same radiopharmaceutical to treat 17 patients with refractory solid tumours or solitary metastases [3]. Complete remission was seen in 7 patients (41 %), and partial remission in 29 % (5 patients).…”

mentioning

confidence: 89%

Interventional nuclear medicine

McCready

Dizdarevic

Aplin

2013

Eur J Nucl Med Mol Imaging

View full text Add to dashboard Cite

Interventional radiology is well established and has been described as the use of minimal invasive surgery performed with the aid of simultaneous radiological imaging. It is surprising that interventional nuclear medicine has not been developed. Interventional nuclear medicine would employ a similar approach where, with the aid of a simple intervention radionuclide, treatment can be provided for benign and malignant pathology. The main difference between interventional radiology and nuclear medicine is that while the former employs an anatomical approach with radiofrequency, ultrasound and cryotherapy ablating a volume which is larger than the lesion, the nuclear medicine approach can use some aspect of physiology to locate the radiopharmaceutical within the target volume and especially any microscopic extension of the pathology.Probably the first attempt at interventional nuclear medicine involved the use of 32 P-labelled colloid. Order and colleagues in the USA injected the 32 P colloid into pancreatic carcinoma, a disease which is resistant to external beam radiation and many forms of chemotherapy [1]. Westlin and colleagues also treated patients with pancreatic tumours with 32 P colloid [2]. Firusian and Dempke used the same radiopharmaceutical to treat 17 patients with refractory solid tumours or solitary metastases [3]. Complete remission was seen in 7 patients (41 %), and partial remission in 29 % (5 patients). 32P gives very high radiation doses not possible with external beam radiotherapy, but the fact that these studies have not been followed up could be because the high interstitial tumour pressure means that the colloid spread is very limited and the high injection pressure required, at least in pancreatic tumours, makes the technique somewhat dangerous for the operator [4]. The difficulty in injecting the radiopharmaceutical is probably due to the colloid stabilizer.In this issue of the journal, Botta et al. report the development of the concept of using a limited diffusion radiopharmaceutical with multiple injections for the treatment of prostate cancer [5]. The use of 90

show abstract

“…4 Our laboratory has shown that the effective doxorubicin concentrations in human prostate tumor histocultures far exceed the clinically achievable plasma concentrations delivered by intravenous administration (ie, 2 m M or 3.4 μg/mL vs <200 nM or 345 ng/mL). 6 , 7 Regional chemotherapy, which has been used clinically to treat other types of cancer, including bladder, skin, ovarian, colon, brain, and pancreatic cancer, [8][9][10][11][12][13][14][15][16][17][18] is an alternative approach to delivering high drug concentrations to the prostate.…”

Section: Introductionmentioning

confidence: 99%

Biodegradable intraprostatic doxorubicin implants

Ortiz

et al. 2007

AAPS J

View full text Add to dashboard Cite

Systemic chemotherapy is not effective in the treatment of prostate-confi ned cancer. We developed biodegradable, doxorubicin-loaded cylinders for intraprostatic implantation and evaluated the feasibility of using regional intraprostatic drug therapy to treat prostate-confi ned cancer. Cylinders were prepared using poly(lactide-co-glycolide) (PLG) or PLG co polymers. The in vitro and in vivo drug release, intraprostatic pharmacokinetics, and histopathology in dogs implanted with the cylinders were studied. The doxorubicin-loaded cylinders made of PLG polymers of 7.9 to 54 kDa molecular weight (MW) had a diameter of ~800 m m, drug loading of 10% to 30% (wt/wt), and even distribution of crystalline drug throughout the matrix. Burst release varied from 3% to 73%, and 7-day cumulative release from 4% to 90%. Decreasing polymer MW and increasing drug loading were associated with higher initial burst release and overall release rates. The in vivo drug release from cylinders (33-kDa PLG, 30% drug loading) in dog prostates was rapid (~80% in 48 hours). Spatial drug distribution, visualized using confocal fl uorescence microscopy, showed high concentrations confi ned to the lobule containing the implant (referred to as the implanted lobule), with steep concentration gradients over the septa separating the lobules. Concentrations in the implanted lobule were about 8 times higher than concentrations delivered by an intravenous injection. The implants caused necrotic cell death in the implanted lobule, without damage to prostatic nerve bundles or the urethra. These results indicate the feasibility of using biodegradable PLG cylinders as intraprostatic implants to selectively deliver high drug concentrations to prostate tissue.

show abstract

An early Phase II study of intratumoral P-32 chromic phosphate injection therapy for patients with refractory solid tumors and solitary metastases

Cited by 39 publications

References 12 publications

Complete Tumor Response Following Intratumoral 32P BioSilicon on Human Hepatocellular and Pancreatic Carcinoma Xenografts in Nude Mice

Complete Tumor Response Following Intratumoral 32P BioSilicon on Human Hepatocellular and Pancreatic Carcinoma Xenografts in Nude Mice

Interventional nuclear medicine

Biodegradable intraprostatic doxorubicin implants

Contact Info

Product

Resources

About