monoclonal Flashcards
what is hybridoma?
- hybrid cells produced by the fusion of short-live B cell and an immortal myeloma cell.
- Used to continuously produce a single type of antibody respond to specific antigen
Characteristic of hybridomas
- unlimited life span
- unique cell surface antigens allow specific antibody target
- used in monoclonal antibody production
- murine characteristics
- highly pure and uniformed antibody
what is antibodies?
Immunoglobulins produced by B lymphocytes or plasma cells in response to an antigen
what is antigens?
large molecule recognized as foreign by the immune system
what is epitopes?
binding site
characteristic of IgG?
Reacts to foreign substance
- form Ag-Ab
- enhances phagocytosis
- protect fetus and newborn
Identify the specific type of cancer Cd206 and CD20
- CD206 applies to Tilmanocept
- CD20 relates to the protein on the surface of B-cell lymphoma
how antibody localization?
tumors grows > blood flow decrease especially to the interior > venous flow is slow > antibodies travel through interstitial spaces and attach to cell close to the capillaries > antibodies that become attached tend to stay attached
Monoclonal antibody Production step
- antigen inject to mouse (cancer specific not patient specific)
- Wait 4-6 weeks: B lymphocyte cells to produce antibodies in response to antigen
- Scarifice the mouse and remove the spleen
- isolate B lymphocytes from its spleen
- Fuse B-lymphocytes with myeloma cells to create a hybridoma
- Grow hybridoma in HAT medium (Hypoxanthine, aminopterin, thymidine)
- check secretion from different test tube to has the highest specificity
- best antibody mass produced in growth media for each specific cancer
What is monoclonal antibodies?
highly specified to an individual epitope on an antigen. the serum obtained consists of one antibody type
what is poly clonal antibodies?
large amount which are non-specific. Able to recognize multiple site. some may react to more than one antigen
HAMA reaction?
- mouse antibodies inject to human > immune system develops antibodies against the foreign mose protein in the Fc region
- no HAMA reaction with 1st dose ( no antibodies present)
- 2nd injection > immune recognized the mouse protein as foreign > mounts an immunological response > causes binding to the newly injected mouse antibody > leaves less antibody available to bind with the desired tumor antigen > increased liver concentration > cleared more rapidly from the vascular space
Symptom of HAMA reaction
mild: fever, hives
severe: shortness of breath, hypotension
fatal: anaphylaxis
monoclonal antibody terminology
- omab: murine (0% human)
- ximab: chimeric (65% human)
- zumab ( >90% human)
- umab (100% human)
indication zevalin
not 1st line therapy
Relapsed (come back), refractory (not responding to treatment), transformed ( lower grade to higher graded), follicular ( abnormal B-lymphocyte)
Contraindication zevalin
- 25% involvement bonemarrow
- impaired bone marrow: stemcell bonemarrow transplant, > 25% active marrow, < 100000 platelet count, < 1500 neutrophil count
- Type 1 reaction or anaphylactic reaction to murine
Patient preparation to zevalin
- Screen HAMA
- must receive infusion of COLD rituximab 4 hrs prior to blocks any CD20
Theranostic term?
Zevalin loosely
combine diagnose and therapy
Theranostic dose and imaging
- diagnostic: lowdose 5mCi In-111 Zevalin 67hr tp, 173/247 keV look at distribution patterns of tracer. labeled antibody molecule find specific antigen and location of the tumor
- therapeutic: higher energy Y90 zevalin 32mCi, 64.1 hr tp, beta 2.281 MeV done 7-9 days after diagnostic imaging
Zevalin Rp
used for chemotherapy in Non- Hodgkin’s lymphoma chimeric MAb to CD20.
5 mCi over 10 min infusion with 10ml saline.
adverse reactions w/n 48 hrs
Zevalin imaging
large FOV SPECT/CT MEPH collimator
energy window 15-20% at 171 and 245 keV
Anterior and posterior CAP at 2-24 hrs and 48-72 hr
WB scan 7cm/min
Normal uptake zevalin
liver, spleen, kidney, bladder and bowel.
Assess distribution of zevalin
blood poool activity decrease
When treatment of zevalin cannot be done
if increased activity in lung, liver, heart, urinary tract or bowel
Altered distribution of zevalin
Uptake in the area of the tumor is not considered altered distribution
Altered distribution of zevalin is seen in intense localization in bone marrow, reticuloendothelial uptake.
Abnormal increased uptake in organs. lung uptake greater than liver. kidney uptake greater than liver, fixed areas of uptake in bowel greater than liver
Treatment zevalin
7-9 days after imaging
pre-treat with rituximab 4hr before zevalin injection
Dose treatment zevalin
0.4 mCi/kg (max 32mCi) of Y90 zevalin beta emitter
indication of neuroendocrine tumor’s
pituitary adenomas
pancreatic islet cell neoplasms
pheochromocytoma
neuroblastoma
paragangliomas
gastrinomas
small cell lung cancers
detection and localization of meningiomas
carcinoid and other tumor benefit from octreotide therapy
diagnosis of rejection in cardiac transplant
Patient prep octreotide therapy
unlabeled octreotide medication stopped 3 day before
well hyrated 1 day before and 24hrs after
- bowel prep and enema
prep for insulinoma
- recent CT film
octreoscan dose
6 mCi In111- pentetreotide with 10ml saline
octreoscan imaging
at 4 and 24 hours post inj optional 48hrs
energy 173, 247 (20% window)
WB anterior and posterior 3cm/min with MEPH collimator
CAP statics 10-15 minutes each. lateral for head if imaged
Spect at 4 hrs 64 image with 30sec/frame
normal uptake in octreoscan
liver, spleen, kidneys, unrinary bladder and bowel
Ga68 dotatate info
Ge68/Ga68 generator
ge Tp 271 days
Ga Tp 68 min
Indication Ga68 dotatate
use in somatostatin receptor positive neuroendocrine tumors
