Radiopharmaceuticals in preclinical and clinical development for monitoring of therapy with PET

Abstract

This review article discusses PET agents, other than (18)F-FDG, with the potential to monitor the response to therapy before, during, or after therapeutic intervention. This review deals primarily with non-(18)F-FDG PET tracers that are in the final stages of preclinical development or in the early stages of clinical application for monitoring the therapeutic response. Four sections related to the nature of the tracers are included: radiotracers of DNA synthesis, such as the 2 most promising agents, the thymidine analogs 3'-(18)F-fluoro-3'-deoxythymidine and (18)F-1-(2'-deoxy-2'-fluoro-beta-d-arabinofuranosyl)thymine; agents for PET imaging of hypoxia within tumors, such as (60/62/64)Cu-labeled diacetyl-bis(N(4)-methylthiosemicarbazone) and (18)F-fluoromisonidazole; amino acids for PET imaging, including the most popular such agent, l-[methyl-(11)C]methionine; and agents for the imaging of tumor expression of androgen and estrogen receptors, such as 16beta-(18)F-fluoro-5alpha-dihydrotestosterone and 16alpha-(18)F-fluoro-17beta-estradiol, respectively.

FIGURE 1

(A) ¹⁸F-FLT. (B) ¹⁸F-FMAU.

FIGURE 2

Newly diagnosed glioblastoma. (A) MRI (contrast-enhanced T1-weighted image) shows large area of contrast enhancement in right frontal lobe. (B and C) Both ¹⁸F-FDG PET (B) and ¹⁸F-FLT PET (C) show increased uptake in same area. (Reprinted with permission of (189).)

FIGURE 3

(A) ⁶⁴Cu-ATSM. (B) ¹⁸F-FMISO.

FIGURE 4

Progression-free survival (left) and cause-specific survival (right) determined from ⁶⁰Cu-ATSM uptake by Kaplan–Meier method. ○ = event in patients with T/M of ≤3.5; ∇ = event in patients with T/M of >3.5. (Reprinted with permission of (83).)

FIGURE 5

(A) Transaxial CT (top left) and ¹⁸F-FDG PET (top right) images of pelvis show intense ¹⁸F-FDG uptake within known cervical tumor at site of cervical mass seen on CT. Transaxial 30- to 60-min summed images of ⁶⁰Cu-ATSM PET (bottom left) and ⁶⁴Cu-ATSM PET (bottom right) of pelvis at same level demonstrate mildly increased uptake within known primary cervical tumor. There are similar patterns of ⁶⁰Cu-ATSM and ⁶⁴Cu-ATSM uptake within tumor. (B) Transaxial coregistered ¹⁸F-FDG PET/CT (top left) and ¹⁸F-FDG PET (top right) images of pelvis show intense ¹⁸F-FDG uptake within known cervical tumor at site of cervical mass seen on CT. Transaxial 30- to 60-min summed images of ⁶⁰Cu-ATSM PET (bottom left) and ⁶⁴Cu-ATSM PET (bottom right) of pelvis at same level demonstrate markedly increased uptake within known primary cervical tumor. There are similar patterns of ⁶⁰Cu-ATSM and ⁶⁴Cu-ATSM uptake within tumor. (Reprinted with permission of (86).)

FIGURE 6

(A and B) Bifrontal glioblastoma multiforme imaged after biopsy in 55-y-old woman. (A) MRI (gadolinium-enhanced T1-weighted image [T1Gd]) shows large, contrast-enhancing, irregular ring-shaped tumor with necrotic center. Non–contrast-enhanced volume was 20 cm³, T1Gd volume was 80 cm³, and T2-weighted volume was 167 cm³. (B) ¹⁸F-FMISO image through same plane. HV was 129 cm³, and T/B_max ratio was 3.0. (C and D) Left temporal glioblastoma multiforme imaged after gross total resection in 53-y-old man. (C) MRI (T1Gd) shows only blood products and no residual contrast-positive disease. Non–contrast-enhanced volume was 1 cm³, T1Gd volume was 7 cm³, and T2-weighted volume was 37 cm³. (D) ¹⁸F-FMISO image through same plane. HV was 5.3 cm³, and T/B_max ratio was 1.6. (Reprinted with permission of (97).)

FIGURE 7

Imaging of 49-y-old woman who had been previously treated for glioblastoma multiforme with tumor resection and conventional radiotherapy at dose of 60 Gy. (A) T1-weighted MR image obtained with contrast medium 13 mo after initial surgery showed contrast-enhanced lesion in left frontal lobe. (B) ¹¹C-MET PET image showed obvious accumulation of tracer corresponding to abnormality on MR image. Mean lesion-to-normal tissue ratio was 1.70. Recurrent tumor was pathologically confirmed by second surgery. (Reprinted with permission of (106).)

FIGURE 8

(A) ¹⁸F-FES. (B) ¹⁸F-FDHT.

FIGURE 9

Baseline tumor ¹⁸F-FES (left) and percentage change in tumor ¹⁸F-FDG (right) uptake after estradiol challenge in patients who responded and patients who did not respond to endocrine therapy. (Reprinted with permission of (140).)

FIGURE 10

¹⁸F-FDHT (A) and ¹⁸F-FDG (B) scans displayed in maximum-intensity-projection format. This figure demonstrates the contrasting metabolism of the 2 tracers in a patient with metastatic prostate cancer. (Reprinted with permission of (158).)