Knowledge

Biodistribution

Source 📝

82:
muscle, fat, adrenals, pancreas, brain, bone, stomach, small intestine, and upper and lower large intestine, a tumor if present) are placed in pre-weighed containers and weighed, then placed into a device that measures radioactivity (e.g. gamma radiation). Normalizing the tissue radioactivity concentrations to the injected dose gives values in units of percent of the injected dose per gram of organ or biological tissue. The results give a dynamic view of how the compound moves through the animal and where it is retained.
95:
for medical diagnostic imaging in the clinic with two main differences: (1) novel compounds under development may be injected into animals subject to scrutiny and approval of the detailed experimental plan while clinicians can only inject radiolabelled compounds that had been tested rigorously and approved for use in humans; (2) animals usually need to be anaesthetized for the duration of the scan (on the order of minutes) while humans are awake and simply need to stay still during the scan.
216: 73:
medical diagnostic imaging, this then produces a clear diagnostic image (high image contrast), and in radiotherapy leads to an attack of the target (e.g. tumor) while minimizing side effects to non-target organs. Additional factors need to be evaluated in the development of a new diagnostic or therapeutic compound, including safety for humans. From an efficacy point of view, the biodistribution is an important aspect which can be measured by dissection or by imaging.
91:
SPECT images for the various organs of interest. This may include measuring the volume of these organs e.g. from the CT image (rather than weighing the organs as in the dissection procedure) or assessing the radioactivity concentration in a representative part of the organ. Normalizing the tissue radioactivity concentrations to the injected dose gives values in units of percent of the injected dose per milliliter of organ or biological tissue.
94:
A benefit of imaging is that the animals can be anaesthetized for imaging for several or all the required time points, that is few animals are required for this procedure and all of them are kept alive. This is considered a non-invasive procedure. In addition, the procedure is in essence the same as
72:
of certain body parts such as brain or tumors (injecting low doses of radioactivity) or for treating tumors (requiring injection of high doses of radioactivity). In both cases, the compound needs to accumulate in the target organ and any surplus compound present needs to clear the body rapidly. In
90:
Similar to the dissection procedure, animals are injected with a low dose of a radiolabelled compound. At the chosen time points after injection, PET or SPECT images are acquired, typically also a CT or MR image for anatomical reference. The radioactivity concentration is measured from the PET or
81:
For example, a new radiolabelled compound is injected intravenously into a group of 16-20 rodents (typically mice or rats). At intervals of 1, 2, 4, and 24 hours, smaller groups (4-5) of the animals are euthanized, then dissected. The organs of interest (usually: blood, liver, spleen, kidney,
150:
could be imaged in rat brain by coating them with biotinylated iron particles, rendering them visible in MR imaging. The biodistribution of the iron-virus particles was seen to concentrate on the
19:
is a method of tracking where compounds of interest travel in an experimental animal or human subject. For example, in the development of new compounds for PET (
43:
particles, equal in mass to the electron, but with a positive charge). When ejected from the nucleus, positrons encounter an electron, and undergo
257: 171:
Raty JK, Liimatainen T, Wirth T, et al. (October 2006). "Magnetic resonance imaging of viral particle biodistribution
139:. Non-invasive imaging has gained popularity as the imaging equipment has become available for research use from clinics. 107:, gene delivery vectors, such as viruses, can be imaged according either to their particle biodistribution or their 51:
travelling in opposite directions. These gamma rays can be measured, and when compared to a standard, quantified.
124: 20: 291: 286: 250: 281: 276: 136: 108: 296: 243: 8: 231: 24: 192: 65: 184: 131:
of gene delivery vector to be visible by the means of immunohistochemical methods,
132: 69: 227: 151: 112: 270: 147: 196: 104: 44: 188: 128: 215: 98: 48: 40: 36: 223: 32: 28: 143: 120: 116: 111:
pattern. The former means labeling the viruses with a
170: 99:
Non-invasive biodistribution imaging in gene therapy
115:, being visible in some imaging modality, such as 268: 251: 68:compound is one that is suitable either for 35:). This particular class of isotopes emits 54: 258: 244: 269: 59: 210: 13: 14: 308: 127:and latter means visualising the 214: 76: 164: 1: 157: 154:cells of lateral ventricles. 85: 230:. You can help Knowledge by 27:is chemically joined with a 21:positron emission tomography 7: 10: 313: 209: 55:Biodistribution analysis 189:10.1038/sj.gt.3302828 60:Purpose and results 47:which produces two 25:radioactive isotope 292:Molecular biology 287:Clinical research 239: 238: 304: 282:Medical genetics 277:Applied genetics 260: 253: 246: 218: 211: 201: 200: 168: 312: 311: 307: 306: 305: 303: 302: 301: 267: 266: 265: 264: 207: 205: 204: 183:(20): 1440–46. 169: 165: 160: 133:optical imaging 101: 88: 79: 70:medical imaging 64:A useful novel 62: 57: 17:Biodistribution 12: 11: 5: 310: 300: 299: 294: 289: 284: 279: 263: 262: 255: 248: 240: 237: 236: 219: 203: 202: 162: 161: 159: 156: 152:choroid plexus 113:contrast agent 100: 97: 87: 84: 78: 75: 61: 58: 56: 53: 31:(subunit of a 23:) scanning, a 9: 6: 4: 3: 2: 309: 298: 297:Biology stubs 295: 293: 290: 288: 285: 283: 280: 278: 275: 274: 272: 261: 256: 254: 249: 247: 242: 241: 235: 233: 229: 226:article is a 225: 220: 217: 213: 212: 208: 198: 194: 190: 186: 182: 178: 174: 167: 163: 155: 153: 149: 148:baculoviruses 145: 142:For example, 140: 138: 134: 130: 126: 122: 118: 114: 110: 106: 96: 92: 83: 77:By dissection 74: 71: 67: 66:radiolabelled 52: 50: 46: 42: 38: 34: 30: 26: 22: 18: 232:expanding it 221: 206: 180: 177:Gene Therapy 176: 172: 166: 146:-displaying 141: 109:transduction 105:gene therapy 102: 93: 89: 80: 63: 45:annihilation 16: 15: 135:or even by 129:marker gene 39:(which are 271:Categories 158:References 86:By imaging 49:gamma rays 41:antimatter 37:positrons 197:16855615 224:biology 173:in vivo 33:protein 29:peptide 195:  144:avidin 222:This 121:SPECT 228:stub 193:PMID 185:doi 175:". 137:PCR 125:PET 119:or 117:MRI 103:In 273:: 191:. 181:13 179:. 259:e 252:t 245:v 234:. 199:. 187:: 123:/

Index

positron emission tomography
radioactive isotope
peptide
protein
positrons
antimatter
annihilation
gamma rays
radiolabelled
medical imaging
gene therapy
transduction
contrast agent
MRI
SPECT
PET
marker gene
optical imaging
PCR
avidin
baculoviruses
choroid plexus
doi
10.1038/sj.gt.3302828
PMID
16855615
Stub icon
biology
stub
expanding it

Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.