8-A842A Halperin7e_CH29_CROPPED2

654

S E C T I O N I I  Techniques, Modalities, and Modifiers in Radiation Oncology

FIGURE 29.2.  SELEX: A random ssDNA (or ssRNA) library is synthesized and exposed to laboratory equipment and target matrix. The aptamers that bind are considered nonspecific and are removed. The remaining aptamers are exposed to the target protein. Aptamers that don’t bind are removed. Aptamers that bind the target are eluted and PCR amplified. Candidate “sense” strand aptamers are isolated and the SELEX process is repeated in order to refine the selection process. Final candi- dates are cloned and sequenced.

absorbed dose of ionizing radiation to cell death. When the log surviving fraction of irradiated cells is plotted on the ordi- nate and the dose (Gy) is plotted on the abscissa, a cell sur- vival curve is generated (Fig. 29.3). The “hit” that results in most lethal event is a double-strand break (DSB) of DNA. The mathematical term, α , represents the initial slope of the cell survival curve. It is a constant for a given tumor (or tissue) and can be thought of as the probability, per unit of absorbed dose, of creating a lethal DSB. 31 The target is the resulting

cGy per minute. This total dose range for RIT occurs despite overall very low percent injected doses (0.1% to 10.0%) that ultimately localize in target tissue. 30 Regardless, radiation- induced apoptosis still occurs. The most radiosensitive component of a cell is the DNA. Irradiation of tissue results in DNA damage. This damage may be either repaired or result in permanent damage. Permanent damage will cause cell death. By using a target-hit model, the tissue response end point of cell death may be used to relate

TABLE 29.3  APTAMERS FOR CANCER IMAGING AND THERAPY (PRECLINICAL AND CLINICAL) Aptamer Target Condition

Radionuclide

Application

AS1411

Nucleolin

Renal cell carcinoma, non–small cell lung carcinoma, leukemia

None

Therapy

AS1411

Nucleolin

Glial tumor Leukemia

67 Ga

Imaging Therapy Therapy Therapy Therapy Imaging Imaging Imaging Therapy Imaging Imaging Imaging Imaging Imaging Therapy Imaging Therapy Therapy Therapy Therapy Therapy Therapy

Sgc8 TD05 14-16 TTA1

Protein tyrosine kinase 7 (PTK-7) Immunoglobulin μ heavy chains (IGHM)

None None None None

Lymphoma, leukemia

NOX-A12

CXCL12/SDF-1

Glioblastoma, multiple myeloma, solid tumors

p68

Colon cancer Glioblastoma Breast cancer Prostate cancer Prostate cancer

Tenascin-C

111 In, 18 F

AptA, AptB

MUC1 PSMA PSMA

99m Tc

A9

89 Zr

A10

225 Ac 99m Tc 188 Re 111 In 99m Tc 99m Tc None 99m Tc None None None None None

F3 U2

hMMP-9 EGFRvIII

Various cancers, metastases

Glioblastoma

E07

EGFR ErbB2

EGFR-expressing cells HER2-expressing tumors CEA-expressing tumors

Mini 15-8

Apt3, Apt3–amine CEA

A30

HER3

Breast cancer

TTA1 5TR1

Tenascin-C

Breast, colon, lung, glioblastoma Breast, colon, lung, ovary, pancreatic

O-glycan-peptide

None (photodynamic therapy agent)

J18

EGRF

EGFR-expressing tumors

None (gold nanoparticles)

Clone5 CTLA-4 aptamer

Sialyl Lewis X

Sialyl Lewis X–expressing tumors

CTLA-4

CTLA-4 receptor

TGF- β

A07

Chinese hamster ovary

PDGF β -receptor

ST1571

Colon

III.1 Therapy CTLA-4, cytogenic T-cell antigen-4; CXCL2, C-X-C motif chemokine 12; EGFRvIII, epidermal growth factor receptor variant III; HER3, human epidermal growth factor-3; hMMP-9, human matrix metalloprote- ase-9; SDF-1, stromal cell–derived factor-1; TGF- β , transforming growth factor- β . Pigpen Glioblastoma