Fluorine-18-Labeled Benzamide Analogues for Imaging the σ2Receptor Status of Solid Tumors with Positron Emission Tomography

Assessment of tumor response during treatment is one of the most important purposes of imaging. Before the appearance of immunotherapy, response evaluation criteria in solid tumors (RECIST) and positron emission tomography response criteria in solid tumors (PERCIST) were, respectively, the established morphologic and metabolic response criteria, and cessation of treatment was recommended when progressive disease was detected according to these criteria. However, various types of immunotherapy have been developed over the past 20 years, which show novel false positive findings on images, as well as distinct response patterns from conventional therapies. Antitumor immune response itself causes 18F-fluorodeoxyglucose (FDG) uptake in tumor sites, known as “flare phenomenon”, so that positron emission tomography using FDG can no longer accurately identify remaining tumors. Furthermore, tumors often initially increase, followed by stability or decrease resulting from immunotherapy, which is called “pseudoprogression”, so that progressive disease cannot be confirmed by computed tomography or magnetic resonance imaging at a single time point. As a result, neither RECIST nor PERCIST can accurately predict the response to immunotherapy, and therefore several new response criteria fixed for immunotherapy have been proposed. However, these criteria are still controversial, and also require months for response confirmation. The establishment of optimal response criteria and the development of new imaging technologies other than FDG are therefore urgently needed. In this review, we summarize the false positive images and the revision of response criteria for each immunotherapy, in order to avoid discontinuation of a truly effective immunotherapy.

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Erratum: Evaluation of response in patients of metastatic castration resistant prostate cancer undergoing systemic radiotherapy with lutetium177-prostate-specific membrane antigen: A comparison between response evaluation criteria in solid tumors, positron-emission tomography response criteria in solid tumors, European organization for research and treatment of cancer, and MDA criteria assessed by gallium 68-prostate-specific membrane antigen positron-emission tomography-computed tomography

Urology Annals ◽

10.4103/0974-7796.306735 ◽

2020 ◽

Vol 12 (4) ◽

pp. 396

Keyword(s):

Positron Emission Tomography ◽

Solid Tumors ◽

Evaluation Criteria ◽

Emission Tomography ◽

Prostate Specific Membrane Antigen ◽

Castration Resistant Prostate Cancer ◽

European Organization ◽

Positron Emission ◽

Gallium 68 ◽

Specific Membrane

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Phase I, Dose-Escalation Study of BKM120, an Oral Pan-Class I PI3K Inhibitor, in Patients With Advanced Solid Tumors

Journal of Clinical Oncology ◽

10.1200/jco.2011.36.1360 ◽

2012 ◽

Vol 30 (3) ◽

pp. 282-290 ◽

Cited By ~ 459

Author(s):

Johanna C. Bendell ◽

Jordi Rodon ◽

Howard A. Burris ◽

Maja de Jonge ◽

Jaap Verweij ◽

...

Keyword(s):

Positron Emission Tomography ◽

Solid Tumors ◽

Dose Escalation ◽

Emission Tomography ◽

Class I ◽

Advanced Solid Tumors ◽

Dose Escalation Study ◽

C Peptide ◽

Positron Emission ◽

Grade 3

Purpose This phase I dose-escalation study investigated the maximum-tolerated dose (MTD), safety, preliminary activity, pharmacokinetics (PK), and pharmacodynamics of BKM120, a potent and highly specific oral pan-Class I PI3K inhibitor. Patients and Methods Thirty-five patients with advanced solid tumors received daily BKM120 12.5 to 150 mg. Dose escalation was guided by a Bayesian logistic regression model with overdose control. Assessments included archival tumor molecular status, response by Response Evaluation Criteria in Solid Tumors (RECIST), positron emission tomography tracer uptake ([18F]fluorodeoxyglucose positron emission tomography [FDG-PET]), fasting plasma C-peptide, and phosphorylated ribosomal protein S6 (pS6) in skin biopsies. Results Overall, treatment was well tolerated. Dose-limiting toxicities were grade 2 mood alteration (80 mg), grade 3 epigastralgia, grade 3 rash, grade 2 and grade 3 mood alteration (100 mg), and two grade 4 hyperglycemia (150 mg). The MTD was 100 mg/d. Frequent treatment-related adverse events included rash, hyperglycemia, diarrhea, anorexia, and mood alteration (37% each); nausea (31%); fatigue (26%); pruritus (23%); and mucositis (23%). BKM120 demonstrated rapid absorption, half-life of ∼40 hours, ∼three-fold steady-state accumulation, dose-proportional exposure, and moderate interpatient variability. One patient demonstrated a confirmed partial response (triple-negative breast cancer); seven patients (20%) were on study for ≥ 8 months. BKM120 demonstrated dose-dependent pharmacodynamic effects on [18F]FDG-PET, fasting C-peptide, fasting blood glucose, and pS6. No significant trends were seen to correlate tumor molecular alterations with clinical activity. Conclusion This study demonstrates feasibility and proof-of-concept of class I PI3K inhibition in patients with advanced cancers. BKM120, at the MTD of 100 mg/d, is safe and well tolerated, with a favorable PK profile, clear evidence of target inhibition, and preliminary antitumor activity.

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