The New Golden Era for Radioimmunotherapy: Not Just for Lymphomas Anymore

Tomblyn, Michael; Katin, Michael J.; Wallner, Paul E.

doi:10.1177/107327481302000109

Cited by 32 publications

(20 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although radioimmunotherapy has clearly been established as an effective treatment strategy for patients with lymphoma (36,37) in solid tumors, radioimmunotherapy alone has had modest response rates, and the addition of chemotherapy has emerged as an important strategy to improve response rates (34). The optimization of antibody kinetics (e.g., multistep targeting) and isotopes (e.g., 177 Lu) has also emerged as an important factor in improving response rates (36,38).…”

Section: Discussionmentioning

confidence: 99%

“…The combination of radioimmunotherapy with chemotherapy to induce enhanced antitumor effects has been extensively explored in preclinical models (23)(24)(25)(26)(27)(28) and in a small number of phase I/II studies in patients with advanced solid tumors, with a suggestion of antitumor activity in some (29)(30)(31)(32)(33)(34). The aim of this approach is to use chemotherapy as a radiosensitizer, so that cancer cell cycle is arrested in the radiosensitive G(2)/M phase and efficacy is improved.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Targeted Chemoradiation in Metastatic Colorectal Cancer: A Phase I Trial of ¹³¹I-huA33 with Concurrent Capecitabine

et al. 2014

View full text Add to dashboard Cite

huA33 is a humanized antibody that targets the A33 antigen, which is highly expressed in intestinal epithelium and more than 95% of human colon cancers but not other normal tissues. Previous studies have shown huA33 can target and be retained in a metastatic tumor for 6 wk but eliminated from normal colonocytes within days. This phase I study used radiolabeled huA33 in combination with capecitabine to target chemoradiation to metastatic colorectal cancer. The primary objective was safety and tolerability of the combination of capecitabine and 131 I-huA33. Pharmacokinetics, biodistribution, immunogenicity, and tumor response were also assessed. Methods: Eligibility included measurable metastatic colorectal cancer, adequate hematologic and biochemical function, and informed consent. An outpatient scout 131 I-huA33 dose was followed by a single-therapy infusion 1 wk later, when capecitabine was commenced. Dose escalation occurred over 5 dose levels. Patients were evaluated weekly, with tumor response assessment at the end of the 12-wk trial. Tumor targeting was assessed using a γ camera and SPECT imaging. Results: Nineteen eligible patients were enrolled. The most frequently observed toxicity included myelosuppression, gastrointestinal symptoms, and asymptomatic hyperbilirubinemia. Biodistribution analysis demonstrated excellent tumor targeting of the known tumor sites, expected transient bowel uptake, but no other normal tissue uptake. 131 I-huA33 demonstrated a mean terminal half-life and serum clearance suited to radioimmunotherapy (T 1/2 β, 100.24 ± 20.92 h, and clearance, 36.72 ± 8.01 mL/h). The mean total tumor dose was 13.8 ± 7.6 Gy (range, 5.1-26.9 Gy). One patient had a partial response, and 10 patients had stable disease. Conclusion: 131 I-huA33 achieves specific targeting of radiotherapy to colorectal cancer metastases and can be safely combined with chemotherapy, providing an opportunity to deliver chemoradiation specifically to metastatic disease in colorectal cancer patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Targeted Chemoradiation in Metastatic Colorectal Cancer: A Phase I Trial of ¹³¹I-huA33 with Concurrent Capecitabine

et al. 2014

View full text Add to dashboard Cite

show abstract

“…La RIT utilisant des émetteurs β -a montré son efficacité en cancérologie, au niveau préclinique et en clinique. Elle a surtout montré son efficacité en hématologie, dans le traitement des lymphomes non hodgkiniens où elle est devenue un traitement de référence en complément de la chimiothérapie [3][4][5][6][7][8]. À ce jour, les deux seules applications de la radioimmunothé rapie homologuées par la FDA (food and drug administration, « agence américaine des produits alimentaires et médicamenteux ») utilisent des émetteurs β …”

Section: Revuesunclassified

Radio-immunothérapie alpha

Ménager¹,

Gorin²,

Fichou³

et al. 2016

Med Sci (Paris)

View full text Add to dashboard Cite

> La radioimmunothérapie alpha (RITα) est une thérapie anticancéreuse vectorisée utilisant généralement un anticorps monoclonal spécifique d'un antigène tumoral couplé à un émetteur de particules α. Les émetteurs α représentent un outil idéal pour éradiquer les tumeurs disséminées ou les métastases. De récentes données démontrent que les rayonnements ionisants, en plus de leur cytotoxicité directe, peuvent aussi induire une immunité antitumorale efficace. Les effets biologiques de l'irradiation pourraient donc être utilisés pour potentialiser la réponse à différents types d'immunothérapie, et ainsi ouvrir la voie au développement de nouvelles thérapies combinant RITα et immunothérapies. < radionucléide. Le choix du radionucléide repose sur des considérations pratiques (le coût, la disponibilité, le type de techniques de radiomarquage et la facilité d'utilisation), le type d'émission du radioélément, le transfert d'énergie linéique (TEL : quantité d'énergie transférée au milieu par la particule incidente, par unité de longueur de la trajectoire en keV 1 /µm) et la demi-vie physique du radioisotope (durée nécessaire pour que la moitié des noyaux radioactifs d'une source se soient désintégrés) [2]. Cette dernière doit être, autant que possible, en adéquation avec la pharmacocinétique du vecteur utilisé, afin de délivrer la plus grande dose possible de radioactivité à la tumeur après l'injection. Une demi-vie trop courte entraînera un nombre élevé de désintégrations avant d'atteindre la cible. À l'inverse, une demi-vie trop longue engendrera un grand nombre de désintégrations du radionucléide pendant la phase d'éli-mination du vecteur, rendant le radioimmunoconjugué plus toxique. La demi-vie doit également être compatible avec les applications cliniques et la prise en charge du patient. Ainsi, le temps nécessaire au transfert du radionucléide du site de production jusqu'à l'hôpital, 1 1 keV (kiloélectronvolts) = 10 3 eV ; 1 MeV (megaélectonvolts) = 10 6 eV.

show abstract

“…RIT has shown high potential as an adjuvant treatment in many types of malignancies [1][2][3]. However, a limitation of treatments with radiolabeled antibodies is that they typically require several hours after intravenous (i. v.) injection to localise the tumour cells.…”

Section: Introductionmentioning

confidence: 99%

Biotinylated and Chelated Poly-L-Lysine as Effector for Pretargeting in Cancer Therapy and Imaging

Lutz

Bäck

Aneheim

et al. 2016

Int J Pharm Pharm Sci

View full text Add to dashboard Cite

Objective: The aim of this study was to synthesise and evaluate polylysine-based effectors for pretargeted radioimmunotherapy and imaging. These molecules can readily be size-modified and charge-modified to decrease the renal uptake of radioactivity, which is often a major problem for small radiolabeled molecules. Several chelators and biotin molecules (for antibody-streptavidin-binding in vivo) are also easily incorporated into one structure because of the polylysine. Methods:The effectors were synthesised using poly-L-lysine, NHS-LC-biotin, CHX-A''-DTPA or p-SCN-Bn-DOTA and succinic anhydride. They were characterised, labelled with Results: Radiochemical purities between 97.4±0.6 % and 99.6±0.1 % and decay-corrected yields of 80.2±2.4 % after purification were achieved with the radiolabeled molecules, as well as a specific activity of 7.6 × 10 3 Keywords: Pretargeting, Radiometals, Polylysine, Radioimmunotherapy, Radioimmunoimaging, Kidney GBq/µmol. The avidin binding capacity was 94.4±1.9%. The kidney uptake study demonstrated a reduction of renal absorbed dose by 80% when modifying the molecular size and charge. Conclusion:The synthesised polylysine-based effectors show potential for further in vivo evaluation in pretargeted radioimmunotherapy and imaging.

show abstract

The New Golden Era for Radioimmunotherapy: Not Just for Lymphomas Anymore

Cited by 32 publications

References 112 publications

Targeted Chemoradiation in Metastatic Colorectal Cancer: A Phase I Trial of ¹³¹I-huA33 with Concurrent Capecitabine

Targeted Chemoradiation in Metastatic Colorectal Cancer: A Phase I Trial of ¹³¹I-huA33 with Concurrent Capecitabine

Radio-immunothérapie alpha

Biotinylated and Chelated Poly-L-Lysine as Effector for Pretargeting in Cancer Therapy and Imaging

Contact Info

Product

Resources

About

The New Golden Era for Radioimmunotherapy: Not Just for Lymphomas Anymore

Cited by 32 publications

References 112 publications

Targeted Chemoradiation in Metastatic Colorectal Cancer: A Phase I Trial of 131I-huA33 with Concurrent Capecitabine

Targeted Chemoradiation in Metastatic Colorectal Cancer: A Phase I Trial of 131I-huA33 with Concurrent Capecitabine

Radio-immunothérapie alpha

Biotinylated and Chelated Poly-L-Lysine as Effector for Pretargeting in Cancer Therapy and Imaging

Contact Info

Product

Resources

About

Targeted Chemoradiation in Metastatic Colorectal Cancer: A Phase I Trial of ¹³¹I-huA33 with Concurrent Capecitabine

Targeted Chemoradiation in Metastatic Colorectal Cancer: A Phase I Trial of ¹³¹I-huA33 with Concurrent Capecitabine