A recent publication from the Precirix team in collaboration with Minerva Imaging evaluated the biodistribution of the biodistribution kinetics and dosimetry of radiolabeled 4AH29, a FAP-targeting single-domain antibody, in Göttingen minipigs.

Biodistribution and blood clearance of [131I]I-GMIB-4AH29

SPECT/CT imaging in male and female minipigs showed rapid renal clearance of [131I]I-GMIB-4AH29, with highest uptake observed in the kidneys and bladder. Biodistribution was similar between sexes, although females showed slightly lower liver and bone marrow uptake. Most organs exhibited low tracer uptake at 3 h post-injection and progressive clearance over time. Blood levels decreased rapidly, confirming fast systemic elimination. No compound-related adverse effects were observed, indicating good tolerability during the study period.

 

Figure 1. Biodistribution and blood clearance of [131I]I-GMIB-4AH29 in male (n = 3) and female (n = 3) Göttingen minipigs. SPECT/CT maximum-intensity projection of A) male B) female minipigs injected with [131I]I-GMIB-4AH29. K=Kidney, B=Bladder, P.D. = Preputial Diverticulum. C) %IA/g in blood. D) %IA/g in kidneys. E) %IA/g in bone marrow. F) %IA/g in liver. G) %IA/g in all evaluated organs. Göttingen male (n = 3) and female (n = 3) minipigs, data represented as mean ± SEM.

Figure 1. Biodistribution and blood clearance of [131I]I-GMIB-4AH29 in male (n = 3) and female (n = 3) Göttingen minipigs. SPECT/CT maximum-intensity projection of A) male B) female minipigs injected with [131I]I-GMIB-4AH29. K=Kidney, B=Bladder, P.D. = Preputial Diverticulum. C) %IA/g in blood. D) %IA/g in kidneys. E) %IA/g in bone marrow. F) %IA/g in liver. G) %IA/g in all evaluated organs. Göttingen male (n = 3) and female (n = 3) minipigs, data represented as mean ± SEM.

Biodistribution and blood clearance of [111In]In-DOTA-4AH29

SPECT/CT imaging of male and female Göttingen minipigs showed that [111In]In-DOTA-4AH29 was rapidly cleared via the kidneys, with highest uptake in the kidneys and bladder. Blood activity decreased quickly in both sexes, and biodistribution was largely comparable, with females showing slightly lower liver uptake and slightly higher kidney uptake. Most other organs exhibited low tracer uptake and progressive clearance over time. No compound-related adverse effects were observed, indicating good tolerability.

 

Figure 2. Biodistribution and blood clearance of [111In]In-DOTA-4AH29 in male and female Göttingen minipigs. SPECT/CT maximum-intensity projection of A) male B) female minipigs injected with [111In]In-DOTA-4AH29. K=Kidney, B=Bladder. P.D. = Preputial Diverticulum C) %IA/g in blood. D) %IA/g in kidneys. E) %IA/g in bone marrow. F) %IA/g in liver. G) %IA/g in all evaluated organs. Göttingen male (n = 3) and female (n = 3) minipigs, data represented as mean ± SEM.

Figure 2. Biodistribution and blood clearance of [111In]In-DOTA-4AH29 in male and female Göttingen minipigs. SPECT/CT maximum-intensity projection of A) male B) female minipigs injected with [111In]In-DOTA-4AH29. K=Kidney, B=Bladder. P.D. = Preputial Diverticulum C) %IA/g in blood. D) %IA/g in kidneys. E) %IA/g in bone marrow. F) %IA/g in liver. G) %IA/g in all evaluated organs. Göttingen male (n = 3) and female (n = 3) minipigs, data represented as mean ± SEM.

Biodistribution and blood clearance of [111In]In-DOTA-4AH29

Human dosimetry estimates were similar between males and females for [131I]I-GMIB-4AH29, [111In]In-DOTA-4AH29, and extrapolated [177Lu]Lu-DOTA-4AH29 and [225Ac]Ac-DOTA-4AH29. The bladder received the highest absorbed dose for [111In]In-DOTA-4AH29 and [177Lu]Lu-DOTA-4AH29, whereas the kidneys were the dose-limiting organ for [131I]I-GMIB-4AH29 and [225Ac]Ac-DOTA-4AH29. Despite the relatively high bladder dose, the estimated exposure remained below established bladder radiation limits.

Using a kidney dose limit of 23 Gy, the maximum administered activities were estimated at 28 GBq for [131I]I-GMIB-4AH29, 39 GBq for [177Lu]Lu-DOTA-4AH29, and 32 MBq for [225Ac]Ac-DOTA-4AH29. Bone marrow doses were low for the 131I and 177Lu variants and higher for the 225Ac variant, corresponding to maximum tolerated activities of 53 GBq, 148 GBq, and 75 MBq, respectively, based on a 2 Gy bone marrow limit. Thyroid exposure from [131I]I-GMIB-4AH29 was minimized by Lugol pretreatment and remained low.

Whole body effective dose was determined at 6.78E-02 mSv/MBq with [131I]I-GMIB-4AH29, 4.34E-02 mSv/MBq with [177Lu]Lu-DOTA-4AH29, and 2.15E+01 mSv/MBq with [225Ac]Ac-DOTA-4AH29.

Conclusion

Radiolabeled FAP-targeting sdAb 4AH29 was well tolerated in Göttingen minipigs. Dosimetry estimates suggest that clinically relevant administrations of 131I-, 177Lu-, and 225Ac-labeled 4AH29 can be achieved without exceeding kidney or bone marrow dose limits, supporting the clinical translation of 225Ac-4AH29.

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References:

  • Dumauthioz N, Navarro L, Berdal M, Nagachinta S, Eersels J, Gaspariunaite V, Antunes ARP, Dewulf J, Massa S, Jørgensen T, Kristensen LK, Starostka T, Mantzilas D, Lahoutte T, D’Huyvetter M. Pharmacokinetics and dosimetry of radiolabeled FAP-targeting single-domain antibody 4AH29 in Göttingen minipigs. Nucl Med Biol. 2026 Jun 25;158-159:109654. doi: 10.1016/j.nucmedbio.2026.109654. Epub 2026 Jun 25. PMID: 42364406.