title: Changes in lognormal shape parameter guide design of patient-specific radiochemotherapy cocktails.
abstract: Uptake of radiopharmaceuticals and chemotherapeutic drugs is nonuniform at the microscopic level. Their distributions are typically lognormal, suggesting that failure in chemotherapy and targeted radionuclide therapy may be attributable, in part, to the characteristics of this biologically ubiquitous distribution. The lognormal problem can be overcome by using cocktails of 2 or more agents, tailored such that at least 1 agent is strongly incorporated by every cell in the target population. Therefore, critical assessment of the tissue uptake of each cocktail component is warranted.
  
  
  METHODS
  Cellular incorporation of the α-particle-emitting radiochemical ((210)Po-citrate) and 2 anticancer drugs (daunomycin and doxorubicin) was determined using flow cytometry. The role of their lognormal distribution in clonogenic cell survival was evaluated.
  
  
  RESULTS
  The shape parameter of the lognormal distribution was found to be correlated to both intracellular agent concentration and cell survival. Although no difference emerged between the shape parameters for citrate within the first 2 logs of cell kill, those for daunomycin and doxorubicin changed significantly.
  
  
  CONCLUSIONS
  Changes in the value of the lognormal shape parameter and slope of the cellular drug uptake curves can be used to rapidly screen radiopharmaceuticals and other cytotoxic agents to formulate more effective cocktails for cancer therapy.
authors.affiliation: Division of Radiation Research, Department of Radiology, UMDNJ-New Jersey Medical School Cancer Center, Newark, New Jersey 07103, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Akudugu
authors.forename: Prasad V S V
authors.initials: PV
authors.lastname: Neti
authors.forename: Roger W
authors.initials: RW
authors.lastname: Howell
mesh_terms: D000465:Algorithms; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002626:Chemistry, Pharmaceutical; D019343:Citric Acid / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D006224:Cricetinae; D003412:Cricetulus; D003630:Daunorubicin / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D004338:Drug Combinations; D015195:Drug Design; D011059:Polonium / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004338:Drug Combinations; D019275:Radiopharmaceuticals; D019343:Citric Acid; D004317:Doxorubicin; D011059:Polonium; D003630:Daunorubicin