DIENST NUCLEAIRE GENEESKUNDE GOES SOUTH AFRICA

De dienst nucleaire geneeskunde az groeninge heeft een lange historiek van samenwerking met de Universiteit van Pretoria, onder leiding van prof. dr. Mike Sathekge. Zowel prof. dr. Christophe Van de Wiele als prof. dr. Alex Maes zijn al vele jaren als Honorary Professor verbonden aan de Zuid-Afrikaanse Universiteit.

Er is een mutueel gewaardeerde interactie ontstaan, niet enkel onder de artsen, maar ook fysicus Laurence Beels, radiofarmaceut Pieter Jan De Jonghe en hoofdverpleegkundige Filip Lavent delen hun expertise met mensen ter plaatse. In de loop der jaren hebben meerdere stafleden van de medische of paramedische equipe vanuit Zuid-Afrika gedurende een aantal maanden az groeninge bezocht voor een stage of voor specifieke projecten, vaak met de steun van het Internationaal Atoomagentschap (IAEA). Recent nog verbleef prof. dr. Kgomotso Mokoala 2 maanden in az groeninge voor een wetenschappelijk project rond het gebruik van 68Ga-PSMA PET-CT bij prostaattumoren.

Naast het geven van postgraduaatlessen aan Zuid-Afrikaanse assistenten in opleiding of cursussen voor het paramedisch personeel, is een intense wetenschappelijke samenwerking gegroeid, vooral op het gebied van nucleaire therapie. De Universiteit van Pretoria heeft wereldwijd een pioniersrol in de ontwikkeling van radioactief gemerkte PSMA antagonisten voor de behandeling van gemetastaseerde prostaatkanker.

Na initieel werk rond 177Lu-PSMA-617 zijn meer recent ook studies opgestart rond het gebruik van 225Ac-PSMA-617. Uit deze samenwerking komen op regelmatige basis wetenschappelijke artikels. Zo werd in 2022 een artikel over het gebruik van radioactief 225Ac-PSMA-617 geselecteerd voor de cover van het Amerikaans Tijdschrift voor Nucleaire Geneeskunde (Journal of Nuclear Medicine), en meer recent werd in 2023 een artikel gepubliceerd in het Europees Tijdschrift voor Nucleaire Geneeskunde (European

Journal of Nuclear Medicine and Molecular Imaging). Hieronder kan u de abstracten van beide artikels lezen.

MCRPC PATIENTS RECEIVING 225AC-PSMA-617 THERAPY IN POST ANDROGEN DEPRIVATION THERAPY SETTING: RESPONSE TO TREATMENT AND SURVIVAL ANALYSIS

Purpose: proved predictive of both progression-free survival (PFS) and overall survival (OS), and platelet count also proved predictive for PFS. The median estimated OS was 9 mo for patients with a PSA decline of less than 50% but was not yet reached at the latest follow-up (55 mo) for patients with a PSA decline of 50% or more. The estimated median PFS was 22 mo for patients with a PSA decline of at least 50% and 4 mo for patients with a PSA decline of less than 50%. No severe hematotoxicity was noted, and only 3 patients had grade III–IV nephrotoxicity. The commonest toxicity seen was grade I–II xerostomia, observed in 81% of patients.

225Ac-PSMA-617, targeting the prostate-specific membrane antigen (PSMA), which is overexpressed on prostate cancer cells, has shown a remarkable therapeutic efficacy in heavily pretreated patients with metastatic castration-resistant prostate carcinoma (mCRPC). Here, we report on treatment outcome and survival using this novel treatment modality in a series of 53 patients with mCRPC directly after their androgen deprivation treatment (ADT).

Conclusion:

In 91% of 53 patients with mCRPC, treatment with 225Ac-PSMA-617 immediately after ADT resulted in at least a 50% decrease in PSA level. Furthermore, a PSA decline of at least 50% proved the single most important factor predicting PFS and OS after 225Ac-PSMA-617 treatment. Of interest, median OS in patients with a PSA decline of at least 50% was not yet reached at the latest follow-up (55 mo). These favorable results suggest that it would be of major clinical relevance to perform a prospective randomized study comparing 225Ac-PSMA-617 with current standard-of-care treatment options such as enzalutamide, abiraterone acetate, and docetaxel after ADT.

225 AC-PSMA-617 RADIOLIGAND THERAPY OF DE NOVO METASTATIC HORMONE-SENSITIVE PROSTATE CARCINOMA (MHSPC): PRELIMINARY CLINICAL FINDINGS

Purpose:

Methods:

225Ac-PSMA-617 was administered to 53 such patients. 68Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle, and on follow-up to select patients for treatment, determine the activity to be administered, and assess their response. Serial prostate specific antigen (PSA) measurements were obtained for response assessment.

Results:

The median age of the patients was 63.4 y (range,45–83 y). In total, 167 cycles were administered (median, 3; range, 1–7). Forty-eight patients (91%) had a PSA decline of at least 50%, and 51 patients (96%) had any decline in PSA. 68Ga-PSMA PET findings became negative in 30 patients. In the multivariate analysis, a PSA decline of at least 50%

225 Ac-PSMA-617 has demonstrated good anti-tumor effect as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients. No study has previously assessed treatment outcome and survival following 225Ac-PSMA-617 treatment of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC) patients. Based on the potential side effects that are known and explained to the patients by the oncologist, some of the patients refused the standard treatment and are seeking alternative therapies. Thus, we report our preliminary findings in a retrospective series of 21 mHSPC patients that refused standard treatment options and were treated with 225Ac-PSMA-617.

Methods:

We retrospectively reviewed patients with histologically confirmed de novo treatment-naive bone ± visceral mHSPC that were treated with 225Ac-PSMA-617 radioligand therapy (RLT). Inclusion criteria included an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, treatment-naive bone ± visceral mHSPC, and patients refusal for ADT ± docetaxel, abiraterone acetate, or enzalutamide. We evaluated the response to treatment using prostate specific antigen (PSA) response and the progression-free survival (PFS) and overall survival (OS) as well as the toxicities.

Twenty-one mHSPC patients were included in this preliminary work. Following treatment, twenty patients (95%) had any decline in PSA and eighteen patients (86%) presented with a PSA decline of ≥ 50% including 4 patients in whom PSA became undetectable. A lower percentage decrease in PSA following treatment was associated with increased mortality and shorter progression-free survival. Overall, administration of 225Ac-PSMA-617 was well tolerated. The commonest toxicity seen was grade I/II dry mouth observed in 94% of patients.

Given these favorable results, randomized prospective multicenter trials assessing the clinical value of 225Ac-PSMA-617 as a therapeutic agent for mHSPC administered either as monotherapy or administered concomitant with ADT are of interest.